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Moving Closer to a Vaccine for Atherosclerosis – Article by Steve Hill

Moving Closer to a Vaccine for Atherosclerosis – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on April 13, 2018. In this article, Mr. Hill reviews a study published by the La Jolla Institute for Allergy and Immunology, in which the study authors successfully vaccinated atherosclerotic mice. In fact, this method supported Dr. Aubrey de Grey’s early insight – his claim that we must attack plaque altogether.

~ Bobby Ridge, Assistant Editor, July 5, 2019

Scientists could be one step closer to a solution to atherosclerosis by preventing the buildup of plaques that clog the arteries and lead to strokes and heart attacks.

What is atherosclerosis?

Atherosclerosis is the accumulation of cholesterol-containing plaques in the walls of arteries; this causes them to narrow, leading to reduced blood flow, higher blood pressure, and an increased risk of a heart attack or stroke. Atherosclerosis is the number one cause of death globally, and, by far, the highest risk factor for this disease is aging, although there are lifestyle factors, such as poor diet, smoking, obesity, and being sedentary.

Drugs such as statins attempt to manage the symptoms but are not truly effective in combating this disease, as they do not address the underlying cause: the formation of the sticky plaques that clog the arteries. Scientists such as Dr. Aubrey de Grey from the SENS Research Foundation have long been advocating for therapies that remove or prevent the formation of plaques altogether, as this would address the problem directly.

One step closer to a solution

In the journal Circulation, researchers at the La Jolla Institute for Allergy and Immunology have published a new study that supports the possibility that there are ways to prevent the formation of plaques in the first place [1]. The team has reported the successful vaccination of atherosclerotic model mice by using a small piece of protein cut from “bad cholesterol”, which facilitates the formation of plaques.

The vaccine was shown to reduce plaque in the mice, and the team also identified the T cells most likely responsible for positive outcomes in human blood samples as part of the same study. The researchers suggest that this technique could form the basis of a vaccine for people.

The vaccine works by boosting the activity and numbers of a type of T cell responsible for reducing inflammation, which leads to a reduction of plaque formation. We have talked about therapies that modulate the immune system and change the ratio of immune cells multiple times, and it is looking like an increasingly promising avenue of research.

“Bad cholesterol” is an amalgam of cholesterol, which is a lipid, and its carrier, low-density lipoprotein (LDL). In order to create the vaccine, the team engineered a peptide that represents a short section of LDL.

The team mounted this peptide on a scaffold called a tetramer and exposed it to immune cells to see which ones became activated in its presence. They tested human blood from two groups of women, one with plaques and one without, to see which immune cells responded to the presence of the peptide.

They observed that a type of regulatory T cell (Tregs) was activated in both groups, although the numbers of Tregs was much lower in subjects with plaques than subjects without, as were the presence of other types of T cells. This suggests that the function of Tregs is somehow hampered by the inflammation that atherosclerosis causes.

The next generation of vaccines that offer greater utility

As well as having the potential to address atherosclerosis, this research spotlights the utility of next-generation vaccines. The immunogenic component of traditional vaccines is a cocktail of molecules harvested from dead or weakened pathogens, but this approach does not work against non-infectious diseases like cancer and atherosclerosis; these next-generation vaccines are much more specific, as they can regulate the immune response using just a single peptide. This means vaccines that target non-infectious diseases are now possible, and, as they are highly targeted, they should have fewer unwanted side effects.

The results presented in this paper show that an effective vaccine against atherosclerosis is now potentially possible. However, the researchers do caution that there is more research to be done before this vaccine can be translated to human use.

Conclusion

While statins simply try to treat the symptoms, a therapy that prevents the buildup of plaques in the first place would be a very welcome step in the battle against age-related diseases and the suffering they bring. If the therapy can be translated to people, it would make strokes and heart attacks practically a thing of the past, and that day cannot come soon enough.

Literature

[1] Kimura, T., Kobiyama, K., Winkels, H., Tse, K., Miller, J., Vassallo, M., … & Jenkins, M. K. (2018). Regulatory CD4+ T Cells Recognize MHC-II-Restricted Peptide Epitopes of Apolipoprotein B. Circulation, CIRCULATIONAHA-117.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Human Pilot Study Results for Senolytics Published – Article by Steve Hill

Human Pilot Study Results for Senolytics Published – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on January 7, 2019. This article presents the results of a human pilot study that involved the consumption of two promising senolytic drugs, dasatinib and quercetin, to target idiopathic pulmonary fibrosis. The results are promising and constitute a great step forward for senolytics being tested in human clinical trials. Another promising approach is the TAME trial, which is a double-blind randomized controlled clinical trial, to test if Metformin can treat various age-related diseases. 

~Bobby Ridge, Assistant Editor, July 4, 2019

The results from a human pilot study that focused on treating idiopathic pulmonary fibrosis with senescent cell-clearing drugs has been published. The drugs target aged and damaged cells, which are thought to be a reason we age and get sick, and remove them from the body.

Senescent cells and aging

As we age, increasing numbers of our cells become dysfunctional, entering into a state known as senescence. Senescent cells no longer divide or support the tissues and organs of which they are part; instead, they secrete a range of harmful inflammatory chemical signals, which are collectively known as the senescence-associated secretory phenotype (SASP).

Dr. Judith Campisi from the Buck Institute for Research on Aging, along with her research team, identified that senescent cells secreted the various harmful chemicals that characterize the SASP in 2008, which was when interest in senescent cells really began [1]. In 2010, building on this initial research, Dr. Campisi went on to show the link between the SASP and cancer [2].The SASP increases inflammation, harms tissue repair and function, causes the immune system to malfunction, and raises the risk of developing age-related diseases such as cancer. It can also encourage other nearby healthy cells to become senescent via the so-called bystander effect. Therefore, a small number of these cells can cause a great deal of harm.

Normally, senescent cells destroy themselves by a self-destruct process known as apoptosis before being cleared away by the immune system. Unfortunately, as we age, the immune system becomes weaker, and senescent cells start to build up in the body. The accumulation of senescent cells is considered to be one of the reasons why we age and develop age-related diseases.

It has been suggested that the clearance of senescent cells might help address a number of age-related diseases at once, as senescent cells are thought to be one of the fundamental reasons that we age. Drugs that can remove these unwanted, damaged cells are known as senolytics.

Human trial results for senolytics

This new publication by researchers at the Mayo Clinic, including James Kirkland, one of the pioneers of senolytic drugs, shows the results of a pilot study that uses dasatinib and quercetin to treat idiopathic pulmonary fibrosis [3].

Pulmonary fibrosis causes scarring of the lung tissue, which leads to the progressive loss of lung function over time. When the disease’s origin is unknown, it is called idiopathic pulmonary fibrosis, or IPF. The treatment options for this disease are extremely limited with no currently known cure.

The researchers in this new study tested a combination of dasatinib and quercetin, one of the earliest senolytic drug combinations that was tested in mice and shown to have beneficial results, particularly for the cardiovascular system [4-5]. It was also shown in a previous study that clearing senescent cells using dasatinib plus quercetin was able to alleviate idiopathic pulmonary fibrosis (IPF)-related dysfunction in a mouse model of the disease.

Fourteen patients with IPF were recruited for this pilot study, and the initial results, while leaving room for improvement, are promising.

Physical function evaluated as 6-min walk distance, 4-m gait speed, and chair-stands time was significantly and clinically-meaningfully improved (p < .05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health were unchanged. DQ effects on circulating SASP factors were inconclusive, but correlations were observed between change in function and change in SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers r ≥ 0.50).

It should be noted that this was only a small pilot study and that the optimal human dosage and frequency is yet to be established. Typically, the next step is to launch a larger-scale study to establish this dosage.

The researchers also note that these results warrant evaluation of dasatinib plus quercetin in larger, randomized, and controlled trials for senescence-related diseases. In other words, they would like to test senolytics in larger studies for various age-related diseases, and the results certainly support doing exactly that.

Conclusion

These initial results are positive, despite there being plenty of room for improvement. The combination of these two drugs also appears to favor particular cell and tissue types over others, much like other senolytic drugs, which were discovered after dasatinib and quercetin were originally shown to clear senescent cells. It may be that a combination of different senolytics will be needed as a “cocktail” of sorts to fully clear out all the unwanted senescent cells, as different senescent cells appear to use various survival pathways to evade apoptosis, and no single drug can target them all.

We greet these early results positively and look forward to the beginning of larger-scale studies for multiple age-related diseases. Given how senescent cells appear to be implicated in most if not all age-related diseases, there are some exciting possibilities ahead.

Literature

[1] Coppé, J. P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., … & Campisi, J. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS biology, 6(12), e301.

[2] Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual Review of Pathological Mechanical Disease, 5, 99-118.

[3] Nambiar, A., Justice, J., Pascual, R., Tchkonia, T., Lebrasseur, N., Kirkland, J., … & Kritchevsky, S. (2018). Targeting pro-inflammatory cells in idiopathic pulmonary fibrosis: an open-label pilot study of dasatinib and quercitin. Chest, 154(4), 395A-396A.

[4] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[5] Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging cell.[/column]

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

 

Will Increased Lifespans Cause Overpopulation? – Article by Elena Milova and Steve Hill

Will Increased Lifespans Cause Overpopulation? – Article by Elena Milova and Steve Hill

Elena Milova
Steve Hill

Editor’s Note: The U.S. Transhumanist Party features this article by our guests Elena Milova and Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on October 30, 2016. In this article, both authors provide evidence that if aging was cured, then overpopulation would not be an issue. Not only is there a common trend among industrialized nations, in which, when the citizens become healthier, wealthier, and educated, they have fewer children, but there are also projections showing that global population growth is gradually falling and will come to a halt around the time the world’s population reaches 11 billion people.
***
~ Bobby Ridge, Assistant Editor, July 3, 2019

Any discussion of rejuvenation biotechnology almost certainly includes the subject of overpopulation and the objection that medical advances that directly address the various processes of aging will lead to an overpopulated world. Such dire predictions are a common theme in many discussions involving advances in medicine that could increase human lifespans.

Overpopulation is a word that gives the simple fact of population growth a negative connotation. It implies that an increase in the number of people will harm our lives in different ways, such as famine, scarcity of resources, excessive population density, increased risks of infectious diseases, and harm to the environment.

This concern, first raised by the work of 18th century reverend and scholar Thomas Malthus, has been a constant theme in both popular fiction and early foresights related to population growth. However, is it actually well-founded? We will be taking a deeper look at the historical and present population data and showing why overpopulation is unlikely to happen.

To get you started, this video with Bill Gates summarizes some of the key points about population and why a longer-lived and healthy society is good for keeping population growth in check.

What is the population, and how will it grow in the future?

Since the 1960s, both birth rate and population growth have been gradually falling. This will probably lead to a complete halt at 11 billion people near the year 2100. Here is a chart from the United Nations Population Prospects 2015 edition showing the corresponding projections [1].

Fig 1. Population of the world: estimates, 1950-2015, medium-variant projection and 80 and 95 percent prediction intervals, 2015-2100.

Here we can see the continuous, red trend line gradually leveling out into a straight horizontal line. However, before talking about why population growth is predicted to stop, let’s investigate why the population is even growing.

In order to ensure population growth, the number of children born per year must surpass the number of deaths in a given country. Typically, a fertility rate index equal to 2.1 is enough for the population to renew without growing in numbers, but a higher birth rate will lead to stable population growth.

In the illustrations below, you can see the global map of fertility and the projection of population growth by major regions [2]

Fig 2. World Population 2010-2100 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.

Fig 3. Total fertility 2010-2015 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.

The biggest contributors to the present level of population growth globally are India and several African regions, while many countries (especially in Europe) face depopulation because of their low birth rate. In the future, most of the population growth will be due to Africa.

Our intuition may tell us that it is unlikely that the least developed countries would be producing most of the population; after all, the standards of living in developed countries make for better conditions to have more children.

However, in reality, there are many factors that can lead to a decline in birth rate during the transition to a developed country: education (access to education for women typically postpones marriage and childbirth), unemployment (families try to control their family size to use fewer resources), and access to contraceptive techniques and cultural norms of using them, to name just a few [3].

Economic development is known to affect the time of birth; for example, recession encourages childbirth later in life [4]. National policies to combine work and family life also represent an important factor that may affect fertility rate in both directions. Globalization will “deepen” (in a world-systems theory sense) the less technologically advanced countries, making it very likely that the “higher birth rate” issue in these countries will also decline.

There is supporting evidence showing that moving to an advanced, industrialized economy changes the birth rate of immigrants. The fertility rates of immigrants to the US have been found to decrease sharply in the second generation [5]. Other studies demonstrate that the presence of immigrants does not compensate for declining birth rates [6].

Fig 4. Declining birth rate leads to gradual slow down of the population growth. The chart shows a UN projection in population size change in percent until 2100 for major regions[7].

The relationship between the level of the development of a country and fertility can be seen in the next chart. It is worth noting that when the Human Development Index (HDI) becomes higher than 0.85, country development starts promoting the birth rate again [8]. However, this kind of situation is very rare, historically, and therefore not significant enough to shape global population projections.

Fig 5.  Fertility vs HDI Index. Data source: United Nations Human Development Index (HDI), UN – Population Division (Fertility), 2015 Revision, Gapminder. Source: OurWorldInData.org/fertility/.

Thus, the least developed countries are more likely to have higher birth rates because people there have no reason to postpone childbirth, nor are measures for contraception widely accessible. The only factor holding back population growth in these regions may be the high level of child mortality and overall mortality due to infectious diseases and undernourishment.

With sustainable development goals focused on the solution of both problems, Africa has the potential to become the biggest human factory in our history. However, taking into account how fast fertility rates can fall because of the adoption of new technologies, this is far from certain.

Fig 6.  How long did it take for fertility to fall from more than 6 children per woman to fewer than 3 children per woman?  Data source: The data on the total fertility rate is taken from the Gapminder fertility dataset (version 6)  and the World Bank World Development Indicators. Source: OurWorldInData.org.

But won’t we run out of space?

In all projected future scenarios for Africa, its population will continue to grow. Today, there are 7.4 billion people on Earth. We are used to thinking that this is already too much, but is that true? First of all, let’s see how much space on Earth we humans actually take up. In 2012, the team of the project “Per Square Mile” led by Tim de Chant produced an infographic showing how big a city would have to be to house the world’s 7 billion people.

The city limits change drastically depending on which real city is used as the model and what its population density is, but this still gives us an idea of how much of our beautiful planet is really inhabited and how much spare space we still have.

If the projection of population growth by the United Nations is correct, in the next 84 years, there will be about 11 billion people. This means that if all of humanity were concentrated in a land area with a population density similar to New York, it would at most occupy the size of 3 US states by 2100.

2012                                                         2100

Fig 7.  7 bln city with population density of New York/11 bln city with the same population density. From the “Per Square Mile” project by Tim de Chant. Note: the picture at right is modified by the article authors to illustrate the potential growth. The state of Texas is about 700,000 square kilometers, which corresponds to about 7 billion people. The states of Texas, New Mexico (about 315,000 km^2), and Louisiana (about 135,000 km^2) combined represent 1,150,000 square kilometers, which corresponds to about 11.5 billion people by 2100.

Does this mean that population growth is not an issue? From the point of view of the space we humans need, likely so. However, our species’ survival is dependent on many other factors, such as the environment necessary to produce our food and other goods.

Are we going to run out of food?

We should admit that it is about fifty years too late to be concerned about extensive population growth and its consequences, such as famine, because the highest birth rate and population growth was observed from the 1960s to the 1980s. Our population grew by one billion people in just 14 years (going from 3 to 4 billion); however, no big societal or economic challenges were encountered.

Moreover, the next two billion increases in population appeared in 13 and 12 years, respectively [9], but once again, no famine caused by the deficiency of global food production followed [10]. The famines of the second half of the 20th century were provoked by how the food was distributed. Factors such as administrative incompetence of local governments, wars and natural disasters happening several years in a row played the greatest role in creating famine during this period.

Today, global society is taking measures to eradicate hunger worldwide by 2030. This is very likely to be the case, as the number of people suffering from hunger is decreasing fast. In 2012, it was one in eight, while in 2015, it was already one in nine, which corresponds to 795 million people. Below, you can see the Hunger Map by the World Food Program illustrating the progress.

Fig 8. FAO, IFAD and WFP. 2015. The State of Food Insecurity in the World 2015. Meeting the 2015 international hunger targets: taking stock of uneven progress. Rome, FAO. Sources: www.fao.org/publications/sofi/en/ Undernourishment data: FAO Statistics Division (ESS) – www.fao.org/economic/ess

If we compare the food supply in 1965 and in 2007, we can clearly see that overeating is more of a global issue than undernourishment, as in most countries, the calorie intake has grown significantly. This could not have happened if our society was suffering from food underproduction, as the food would not be available to overeat, and problems such as obesity would not be so prevalent.

Fig 9.  Food supply 1965 vs 2007 Source: Gapminder statistics (www.gapminder.org/)

Astoundingly, this means that a population explosion has passed relatively unnoticed – all thanks to the “Green Revolution” (rapid development of new agriculture techniques, such as fertilizers, irrigation and selection). The concern that there will be a food shortage in the future neglects further technological advances such as aquaponics, hydroponics, aeroponics, vertical farming, 3D-printed housing, algae farms, and many other technologies that could provide enough food for all.

The need for more food production represents an excellent opportunity for entrepreneurs, so it is unlikely that the development process of new technologies would suddenly stop, especially taking into account the objective need for rapid changes due to environmental issues.

According to a report by the Food and Agriculture Organization of the United Nations, “Livestock’s long shadow”, in 2006, livestock represented the biggest of all anthropogenic (i.e., due to human activity and with potentially harmful side effects) land uses, taking up to 70% of all agricultural land and 30% of the ice-free terrestrial surface of the planet [11].

Scientists admit that while it is still possible to expand agricultural land in some countries in accordance with the increasing need for food, this expansion cannot go beyond the limits of the carrying capacity of our planet. The report states that livestock is responsible for about 18% of the global warming effect, 9% of total carbon dioxide emissions, 37% of methane and 65% of nitrous oxide. Water use for livestock represents about 8% of all human water use (7% of this being used for feed irrigation).

New technologies can provide solutions for the numerous environmental issues related to traditional farming. For instance, hydroponics offers around 11 times higher yields while requiring 10 times less water than conventional agriculture [12]. The energy needs of a hydroponic facility are much higher (up to 80 times more), but thanks to emerging clean renewable energy technologies, this increased demand may not be an issue [13].

Today, there are many companies engaged in the creation of lab-grown meat, such as Supermeat and Memphis Meats. Making a laboratory into a farm is beneficial in many ways, starting from less pollution and fewer greenhouse gas emissions (mostly caused by animal digestion processes).

Sterile conditions in the lab lead to decreased risk of infections and allow the exclusion of antibiotics from the process of meat production. Lab-grown meat can be designed to contain less fat or even fats and proteins with new characteristics (for instance, essential Omega fatty acids).

With less space necessary for laboratory meat production and no waste, it will be possible to ensure disseminated local production in order to cut transportation time and reduce the usage of preservatives. The same system can be used to grow fish meat as well, thus reducing the impact of fishing and fish-farming on the environment. It is interesting to note that not only meat but also other animal-derived products, such as leather, can be produced in a lab, like is done by Modern Meadow.

There are attempts to create new edible products that taste like meat but are completely without animal ingredients, such as Impossible Foods. The recently created vegan ‘Bloody Burger’ by Impossible Foods “uses 95% less land, 74% less water and emits 87% fewer greenhouse gas emissions than its cattle-derived counterpart”. By concentrating on the heme molecule, the mixture apparently “looks like meat, tastes like meat and sizzles like meat“.

These solutions are also great from an ethical point of view, as this technology can reduce animal suffering. The rate of transition to these new ways of animal product creation is widely dependent on political will and social support. It is important to note that there is also significant progress regarding access to drinking water. During the Millennium Development Goals period (1990-2015), it is estimated that, globally, use of improved drinking water sources rose from 76 per cent to 91 per cent. 2.6 billion people have gained access to an improved drinking water source since 1990.

The MDG target of 88 per cent was surpassed in 2010, and in 2015, 6.6 billion people used an improved drinking water source. There are now only three countries (all located in sub-Saharan Africa and Oceania) with less than 50 per cent coverage, compared with 23 in 1990 [14]. New technologies for cheap water desalination and water collection from the air are also helping to improve the situation.

If population growth is not exactly an issue, then what is?

What we really should be concerned about is the age structure of the population. Regardless of the level of technological development, its core are the people of working age who are producing goods, paying taxes, and supporting the non-working groups, such as children and the elderly – the latter needing the most resources because of the state of their health.

Due to population aging, the share of working-age people is shrinking while the share of people who are at least 60 years old is growing. Population structure change is the most evident in Europe and Northern America, while the “Global South” has not experienced it yet – but will experience it in the next few decades.

Fig 10. Percentage of population in broad age groups by major area in 2015. Source: United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377

Soon, one third of the population worldwide is going to be aged sixty or over, which means more social protection and healthcare expenditures and more working age people involved in nursing the elderly. However, it would be wrong and unjust to see the elderly as a burden, while these people have contributed so much to the incredible progress that our society has made.

They have all the same human rights as everyone, including the right to life and right to health. As age-related health deterioration is the main reason why society has to provide so much support to the elderly, it would be only logical to see the development of rejuvenation biotechnologies as the way to improve the situation.

What would life be like if we introduced rejuvenation technologies globally?

Before the era of universal medicine, people who managed to reach their sixties were still in relatively good health. However, once the onset of age-related diseases began, they died very quickly.

Modern medicine has changed that by slowing down the development of age-related diseases, hence extending the period of productivity. The downside is that this has also extended the period of illness, because treatments to prevent age-related diseases are not yet introduced into universal clinical practice.

In the near future, new interventions to slow down the aging process will become accessible, and then a shift will occur: the period of youth and adulthood will be extended due to better health, and the period of illness will be significantly postponed. In their sixties, people will remain as strong and vital as 40-year-old people are today. Some leading scientists predict that this may also lead to maximum lifespan increases of up to 150 years or more.

This is, of course, hard to prove, because as with many other things in human history, it is a unique situation that has never happened before, but some studies have proposed how aging would look given these three scenarios [15].

Fig 11. A:Pre Universal Medicine, B: Current medicine, C: Slowing aging. Source: Blagosklonny, M. V. (2012). How to save Medicare: the anti-aging remedy. Aging (Albany NY), 4(8), 547-52.

Whilst it is too early to be overly optimistic, we still should mention that apart from these three scenarios, there is a fourth possibility called negligible senescence. Negligible senescence in nature happens when a species does not display signs of aging, regardless of the passage of time. A number of species exhibit negligible senescence, including the rougheye rockfish (Sebastes aleutianus).

The ocean quahog (Arctica islandica) and some kinds of turtles are also negligibly senescent, but they still die because the expansion of their shell ultimately limits their movement. More examples can be found here at the excellent HAGR (Human Ageing Genomic Resources) database.

At some point in time, medical technologies may become so sophisticated that they will be able to bring all of the processes of aging under medical control. If that is the case, then aging will always remain at a subclinical stage, because the repairs to our bodies will keep up the pace with damage accumulation, allowing people to look and feel young for an indefinite period of time.

Most likely, it will take decades for medical science to progress this far, but we should also admit that some of the technologies necessary for this transition already exist, e.g., stem cell therapies, early nanorobots, CRISPR and gene therapies, immunotherapies, senolytics, and geroprotectors (drugs that slow down the aging process).

How will increased lifespan affect population growth?

The possibility of significant life extension using medical interventions was not even considered by the academic community until recent years, so there were not many projections of how increased lifespans and negligible senescence would affect population growth. However, a few years ago, such a projection was done for Sweden.

One of the more realistic scenarios is one where only a small share of the population accepts negligible senescence technologies at the beginning (this could be due to a slow dissemination process, ethical or religious objections that people have to overcome, or a high cost of the new technology) with a gradual increase (1% added to the negligibly senescent group each year). It is assumed that some small share of the population will never accept these technologies and will age in the traditional way.

In this case, population change in Sweden will not lead to population growth but can, to some extent, mitigate the process of depopulation over 100 years of medical innovations [16].

Fig 12. Population projection for a scenario of growing acceptance of antiaging interventions. Projection of the Swedish population until year 2105, assuming the negligible senescence scenario for initially small proportion of population (10%), with growing acceptance rate over time. Life extension interventions start at age 60 years, with 30-year time delay from now.

This might be the likely scenario in most developed countries. Taking into account that new technologies tend to be expensive even for developed countries’ middle classes, the developing countries most possibly will reach the same level of implementation later in time, when their fertility rate will be already affected by the index of development. In this case, the fall of their population growth will be smaller due to decreased population mortality.

In a more optimistic scenario, where all the population has access to negligible senescence technologies and they are applied to everyone who is at least 60 years old, population growth in 70 years will be around 22%. The earlier the application, the bigger the population growth. If negligible senescence technologies are applied at the age of 40, then the estimated population growth will be nearly 47% in 70 years.

Fig 13. Projection of the Swedish population until the year 2105, assuming the negligible senescence scenario. Life extension interventions start at age 60 years, with a 30-year time delay from now.

There are three main conclusions we can make based on this data.

  1. The growing share of people using negligible senescence technologies could help optimize the balance between workforce and retirees, hence maintaining economic development. People who are at least 65 years old will be about one-third of the global population in 2100, so we are talking about 3-4 billion old people who could be healthy and productive or ill and frail, depending on which strategy that global society implements.
  2. Negligible senescence is a synonym of good health, which means that the burden of age-related diseases and their social consequences will be mostly eliminated.
  3. Population growth, surprisingly, will not be as dramatic as is often imagined, leaving a significant period of time for adaptation, adequate measures of population growth control, and new territories’ development.

Is mitigating aging not only a need but also a legal obligation?

Even if negligible senescence remains a long-term goal, the emerging technologies to address the various aging processes [17] represent a unique opportunity to maintain older people in good health, allowing them to enjoy healthier lives, remain active, learn new skills, and contribute to the development of society. We owe them our present well-being. Not only have these people contributed a lot to create the things we have now, including better nutrition, healthcare, and a comfortable and safe habitat, they have also worked hard to change traditions and wisdom and helped to carry the concept of equal human rights forwards. This is why it is especially poignant to understand that geroprotective technologies and their potential are being underestimated and that they are not receiving the level of social approval and support that they rightly deserve.

According to the World Health Organization (WHO) Constitution, the objective of the WHO is “the attainment by all peoples of the highest possible level of health”. It is worth noting that WHO defines health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” [18]. While this definition may seem quite spacious, it was made this way purposefully to ensure that member states’ activities in improving the health of their people would never stop.

Conclusion

The need for constant improvement of health is now a universal consensus.

Aging represents the root cause of severe diseases, such as cancer, Alzheimer’s, stroke, Parkinson’s, heart disease, COPD, type 2 diabetes, osteoarthritis and atherosclerosis, leading to disability of the elderly and to a wide range of negative social consequences, which makes it the perfect target for the global healthcare system [19].

These diseases can only be cured if the actual aging processes are directly addressed and halted while the damage is repaired or reversed by medical interventions. Therefore, according to WHO and United Nations policy, this means that global society has an obligation to eventually cancel aging in order to achieve the highest possible level of health for all people.

Literature

  1. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Volume II: Demographic Profiles (ST/ESA/SER.A/380).
  2. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.
  3. Mather, M. (2012). Fact sheet: The decline in US fertility. Population Reference Bureau, World Population Data Sheet.
  4. Lanzieri, G. (2013). Towards a ‘baby recession’ in Europe?. Europe (in million), 16(16.655), 16-539.
  5. Nargund, G. (2009). Declining birth rate in Developed Countries: A radical policy re-think is required. FV & V in ObGyn, 1, 191-3.
  6. Camarota, S., & Ziegler, K. (2015). The Declining Fertility of Immigrants and Natives. Center for Immigration Studies.
  7. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Key Findings and Advance Tables. ESA/P/WP.241.
  8. Myrskylä, M., Kohler, H. P., & Billari, F. C. (2009). Advances in development reverse fertility declines. Nature, 460(7256), 741-743.
  9. United Nations, Department of Economic and Social Affairs, Population Division (1999). The World At Six Billion. ESA/P/WP.154.
  10. Gráda, C. Ó. (2007). Making famine history. Journal of Economic Literature, 45(1), 5-38.
  11. FAO, U., & Steinfeld, H. (2006). Livestock’s long shadow: Environmental issues and options. Rome:[sn].
  12. Barbosa, G. L., Gadelha, F. D. A., Kublik, N., Proctor, A., Reichhelm, L., Weissinger, E., … & Halden, R. U. (2015). Comparison of land, water, and energy requirements of lettuce grown using hydroponic vs. conventional agricultural methods. International journal of environmental research and public health, 12(6), 6879-6891.
  13. REN21. 2016. Renewables 2016 Global Status Report (Paris: REN21 Secretariat).
  14. Unicef. (2015). Progress on Sanitation and Drinking-Water: 2015 Update and MDG Assessment. World Health Organization: Geneva, Switzerland.
  15. Blagosklonny, M. V. (2012). How to save Medicare: the anti-aging remedy. Aging (Albany NY), 4(8), 547-52.
  16. Gavrilov, L. A., & Gavrilova, N. S. (2010). Demographic consequences of defeating aging. Rejuvenation research, 13(2-3), 329-334.
  17. López-Otín, Carlos et al.(2013). Hallmarks of Aging. Cell , Volume 153 , Issue 6 , 1194 – 1217
  18. World Health Organization. (2014). Basic documents. World Health Organization.
  19. Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., … & Rando, T. A. (2014). Aging: a common driver of chronic diseases and a target for novel interventions. Cell, 159(4), 709.
Elena Milova: As a devoted advocate of rejuvenation technologies since 2013, Elena is providing the community with a systemic vision how aging is affecting our society. Her research interests include global and local policies on aging, demographic changes, public perception of the application of rejuvenation technologies to prevent age-related diseases and extend life, and related public concerns. Elena is a co-author of the book Aging prevention for all (in Russian, 2015) and the organizer of multiple educational events helping the general public adopt the idea of eventually bringing aging under medical control.
***
Steve Hill: Steve serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Alzheimer’s Disease Reversed by Editing a Single Gene – Article by Steve Hill

Alzheimer’s Disease Reversed by Editing a Single Gene – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on April 13, 2018. In this article, Mr. Hill reviews a new study published in Nature that supports the idea that Alzheimer’s disease research efforts should target the ApoE4 gene, and not consider the ApoE3 gene as much, even though  previous research that focused on the ApoE3 gene cured Alzheimer’s disease in mice models. This is a promising step forward for Alzheimer’s research.

~Bobby Ridge, Assistant Editor, July 2, 2019

Researchers at Gladstone Institutes in San Francisco report that a gene variant associated with Alzheimer’s works differently in mice and humans, and they also demonstrate how modifying this gene could potentially prevent the plaques associated with Alzheimer’s from forming and damaging the brain. The new study was published in the journal Nature in January 2018 [1].

An ApoE3 gene variant is associated with Alzheimer’s disease

The gene apolipoprotein E3 (ApoE3) has a variant known as ApoE4, which is associated with the development and progress of Alzheimer’s disease. People with just one copy of the ApoE4 gene are at twice the risk as people without this gene variant. Some people even have two copies of the ApoE4 gene, which makes their risk of Alzheimer’s a staggering twelve times greater.

Both the ApoE genes produce their own forms of ApoE protein, which differ in structure. The ApoE4 protein is fragile and fragments because it cannot function in the same way as the regular ApoE3 protein in human nerve cells. These fragmented protein pieces are associated with the increased production of amyloid-β peptides and tau phosphorylation that are typical of Alzheimer’s disease.

The researchers wanted to find out how ApoE4 is linked to Alzheimer’s disease. They considered the possibility that the increased amyloid-β and tau phosphorylation from the fragmentation of ApoE4 drives disease progression. Another possibility involved the negative consequences of a lack of ApoE3 proteins, as they were replaced by the ApoE4 variant. The team also considered a combination of both of these possibilities.

The team investigated these potential answers by examining the effects of ApoE3 and ApoE4 on human nerve cells. Neurons were created by using pluripotent stem cells taken from volunteers who had either two copies of ApoE3 or two copies of the ApoE4 gene, and the researchers programmed these cells to become the desired type of neuronal cell.

The team compared the ApoE3 and ApoE4 neurons against neurons that were unable to produce either type of the ApoE protein. They discovered that neurons that produced no ApoE protein worked the same as those that produced ApoE3. This confirmed that it was not a lack of ApoE3 causing the problem but that ApoE4 protein alone was linked to Alzheimer’s disease.

This finding also sheds light on why treatments for Alzheimer’s that work in mice fail to translate to humans. The production of amyloid-β in mice is not influenced by ApoE4; this means that treatments that prove effective in mice may not work in humans, as the mouse models of the disease do not emulate the ApoE4-related form of Alzheimer’s that humans get. However, therapies that focus on reducing amyloid-β have worked in mice [2], so while ApoE4 functions differently in mice and humans, this is not the full story of Alzheimer’s. This research does, however, clearly show a way in which mouse models differ from humans, helping to guide future research.

Converting ApoE4 to ApoE3

The results of the study suggest that therapies that seek to modify the ApoE4 gene protein before it fragments might be a way to combat Alzheimer’s. This is how traditional medicine would generally approach the problem, treating the symptoms and not the cause.

However, the researchers took this one step further to a far more robust solution. Rather than simply attempting to treat the consequences of having an ApoE4 gene producing sub-par proteins, they completely removed the problem by using gene therapy to edit the genes and convert them from ApoE4 to ApoE3.

The converted genes ceased to produce the unstable ApoE4 protein and produced the stable ApoE3 version of it instead. This served to correct the problem at the root rather than trying to slap a band-aid on the consequences.

Conclusion

With so many failures to combat Alzheimer’s disease, it is easy to become disillusioned. We have seen mice cured of the disease numerous times, but these cures have failed to translate to humans. These new findings help to progress knowledge in the field and offer potential new ways to defeat Alzheimer’s.

What is refreshing about this study is how the researchers have opted to attack the problem at the root cause: the production of misfolded proteins that lead to the progression of the disease. It is becoming ever more clear that if we are going to make progress on ending age-related diseases, we must target the aging processes themselves, which cause these diseases.

Literature

[1] Yuang, Y. et al. (2018) Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nature Medicine doi:10.1038/s41591-018-0004-z

[2] Hu, X., Das, B., Hou, H., He, W., & Yan, R. (2018). BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions. Journal of Experimental Medicine, jem-20171831.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Meanwhile, in the 1600s… – Hypothetical Dialogue by Nicola Bagalà

Meanwhile, in the 1600s… – Hypothetical Dialogue by Nicola Bagalà

Nicola Bagalà


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Nicola Bagalà, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on January 24, 2019. This article provides an example of a family in the 1600’s having to deal with their children contracting and dying from a fever to shed light on anyone’s contemporary contention for curing age-related diseases. It’s easy for most of us in today’s age to completely support innovation that heals another from their fever before they die, when many would have considered that vile and blasphemous hundreds of years ago. Hopefully we can learn from history and accept that curing all diseases through medical science and innovation is morally superior. 

~Bobby Ridge, Assistant Editor, July 1, 2019

Many people are at the very least iffy about the idea of extending human healthy lifespan through medical biotechnologies that prevent age-related diseases essentially by rejuvenating the body. Even people who accept the possibility that such therapies can be developed are not convinced that developing them is a good idea, and there are only a few arguments that most people use. These arguments can actually be easily adapted to make a case against the medicine that already exists, which the vast majority of people on the planet currently benefit from—and the consensus is virtually universal that people who do not yet benefit from it should be given this opportunity as soon as possible.

The question is: would people who accept these arguments as valid objections to rejuvenation accept them also as valid objections against “normal” medicine? For example, how many present-day people would agree with what these two people from the 1600’s are talking about?


A – Did you hear about John’s son?

B – Yes, he came down with a fever and never recovered. What a tragedy.

A – Indeed. He and his wife had lost three other children to a fever before.

B – Oh, that’s terrible. Did they try to ask for a doctor’s help?

A – They couldn’t afford it for the other children, but when a fourth one became ill, they were so desperate about it that they did all they could to find the money. Anyway, not even the doctor could save the child’s life, even with all the leeches and poultices at his disposal.

B – Of course, I know nothing about medicine, but sometimes I think doctors don’t either. Their practices are a bit… scary, and as far as I have heard, most people they treat die anyway.

A – That may be, but doctors still have the best wisdom and techniques, at least for those who can afford them.

B – Who knows, maybe one day, doctors will actually know how to cure us for real. It could be as simple as drinking a potion or eating some sort of biscuit containing specific medicinal herbs, and in a few days, you’re back on your feet, no matter the disease.

A – That seems like fantasy to me. Doctors have existed for centuries, and they never managed to perform such miracles. If this were at all possible with knowledge and technique alone, wouldn’t one of them have managed to do so by now? Besides, perhaps it is for the best to leave things the way they are; doctors have gone far enough into God’s domain, and I don’t even want to imagine what would happen if they went even farther.

B – That is true. Surely, there must be a reason for all the diseases that plague us. Common folks are more affected, true, but they also take nobles on occasion. It’s difficult to say if this is because commoners sin more than nobles and that this is God’s way of punishing them or because they are more pious and God wants to call them to Himself sooner, but it is obvious that the will of Providence is at play.

A – Exactly. But I think there is more than this to it. Maybe the reason why diseases exist is to make our lives less miserable. Maybe they are blessings in disguise.

B – I don’t understand. They do cause a lot of suffering, not only to the diseased but also their families.

A – That is true, but how much more suffering would they endure if they went on living, especially among us commoners? It might explain why diseases affect common people more than the nobility. They live better lives, so it makes sense for them to live longer and enjoy it; but what about us? Our lives are harder and deprived of all the comforts and luxuries that rich people can afford. Is it worth living longer for us?

B – You speak truth, and I also think that if, one day, doctors will really be able to cure everyone of certain ailments, this will only make poor people’s lives worse. Very few people can afford the services of doctors even though they aren’t of much use; imagine how expensive it would be if they actually could cure you! Rich people would be healthy, and the rest of us would simply have to die knowing that they could be saved if only they had the money.

A – You are right, it is definitely better if there is no cure for anyone rather than a cure that is only for some. But, still, I dream of a day when medicine eventually becomes cheaper, or maybe the commoners won’t be so poor.

B – A day when even the likes of you and me could live in a fairly comfortable house, with our basic necessities covered, without having to work so hard every day to bring just a little food to the table, and while being able to afford the services of a doctor whenever we need one? You dream of Heaven on Earth, friend; it won’t happen until Judgment Day.

A – We won’t be able to achieve this ourselves, even centuries from now?

B – Again, it hasn’t happened until now, I don’t see why it should happen later. Even if it did, the consequences would be even more dire. It’s hard enough as it is to produce enough food for everyone, and if doctors could cure all diseases and everyone was able to afford these cures, there would be far too many mouths to feed. Therefore, in His infinite wisdom, the good God has decided that some of us must fall prey to disease.

A – I see your point, but in such a world where doctors can treat all ailments with their own knowledge, maybe we would be able to produce more food with less work, so that hundreds of millions, maybe even billions, could eat every day, while farming would not be as laborious.

B – You sure have a wild imagination! And how could that be accomplished, pray tell?

A – Perhaps there might be more machines that do work in place of animals, faster and better. Possibly even in place of people.

B – Machines that work the fields without a person maneuvering them? Walking water mills? Clockwork horses? Oh! How about a sewing machine to go with our spinning wheel? My wife would love such a thing, if it could ever exist.

A – We have some machines for some tasks. Why could we not have more?

B – Because they could never work, that’s why. I sure hope you’re never going to talk such nonsense with others, because not everyone has my sense of humor.

A – Maybe you are right. It was a bit of a stretch; windmills and water mills must sit where they are, after all. Diseases may be a necessary evil, as well. I’ve seen people who survived ailments like the one that killed John’s son, and as they grew older, their lives became more and more miserable. Old age was killing them more slowly and with far more cruelty than fever or plague. A poor old man dies on the street if he has no family to care for him or if his family cannot afford it. I would rather die the way John’s son did, surrounded by my loved ones, than as a crippled old man begging under a bridge.

B – Now you’re talking sense, and this is probably one of the most compelling reasons why we should leave diseases alone. Again, maybe it makes sense for the royalty to live that long, because they will not end up dying like old beggars, but for the rest of us, that would be a curse.

A – True. Besides, I suppose that at some point, one would get tired of living and would rather go. I guess this must be why even people who don’t die early in life eventually die of old age; even if you are part of the upper class, what can you possibly look forward to after you’ve seen your children and grandchildren grow up? Even if you know how to read and have a taste for music and the theatre, there are only so many books and so many composers and playwrights.

B – Precisely.

A – Yes, while being able to cure diseases might appear to be a good thing at first, when you think about it, you realize that it would not be.

B – Indeed, and this is what we must always remind ourselves of when disease does strike and sorrow makes us lose our objectivity.


The arguments presented by our two friends from the 1600’s are fundamentally the same ones that a lot of people bring up when they try to rationalize and justify the diseases of old age, saying that the defeat of aging might, at first, appear to be a good thing, but would actually not be that good after all. However, given the knowledge we have today, it is very easy to counter their arguments; in any event, not too many people would agree that the conversation above would have made a good case against vaccines and modern medicine, which have brought infectious diseases under strict control and save countless lives that would otherwise be lost on a daily basis.

Just like the arguments in the conversation above would not be a valid reason to give up on the medicine we are used to, they are not a reason to give up on the medicine of the future—the rejuvenation biotechnologies that might soon prevent and reverse the course of age-related diseases. Claiming otherwise is nothing but a double standard.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. degree in mathematics; an amateur programmer; a hobbyist at novel writing, piano and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Sarah Constantin
Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on May 9th, 2018. In this article Mr. Hill interviews Dr. Sarah Constantin, a researcher with a focus on machine learning at The Longevity Research Institute. This is an excellent article, especially if you want to learn more of the hard science behind longevity research. The topics of the interview range from deep learning being applied to pharmacology, to optimal mouse strains, and ideal areas of research to target age-related diseases.

~Bobby Ridge, Assistant Editor, June 30, 2019

Today, we have an interview with the Longevity Research Institute, a new group that launched in April 2018. The goal of the Institute is to identify therapies that can demonstrably extend healthy human lifespan by 2030 at the latest.

Searching for longevity

There are dozens of compounds and therapies that have been demonstrated to increase the lifespan of mammals. Recently, there have been some impressive examples of rejuvenation in animals using a variety of approaches, including partial cellular reprogramming, stem cell therapy, and senescent cell removal. More importantly, in many of these studies, age-related diseases have been delayed or even reversed.

Unfortunately, very few of these studies have had independent follow-ups or replication, and that is slowing down progress. The Longevity Research Institute is aiming to bridge the gap between basic science and commercial drug development.

It has chosen the field of aging research as its area of focus for one simple reason: age-related diseases are the leading cause of death globally. Heart disease, stroke, cancer, diabetes, Parkinson’s, Alzheimer’s and many more diseases are all caused by the various processes of aging.

The data from hundreds of animal studies tell us that aging is not a one-way process and that the rate of aging is something we can slow down or even reverse. Experimental results show that we can increase the healthy lifespan of animals significantly and delay the onset of age-related diseases in doing so. If we could translate those findings to humans, we could potentially increase the healthy period of life, known as health span, or even increase our lifespan beyond current norms while remaining healthy.

The majority of aging research consists of basic science that focuses on the mechanisms of aging, studies involving invertebrates like worms or fruit flies, and experiments that examine the effect of therapies on biomarkers of aging. However, the Longevity Research Institute believes that the way to find effective treatments that could translate to humans is by testing interventions on mammals to see if they increase lifespan or if they delay or reverse symptoms of aging, such as frailty, cognitive decline, and the prevalence of age-related diseases. Robust mammalian lifespan studies are quite rare in aging research due to their long duration and thus cost; the Institute believes they are worth doing despite this challenge.

Its philosophy is to be skeptical of results that depend on too many uncertain assumptions, such as particular mechanisms of aging or analogies between invertebrate and human biology. It believes that the closest way to measure the health and lifespan of a human is to measure the same things in mammals.

Replicating and Extending Lifespan Results

The majority of studies that have been shown to increase lifespan are rarely independently replicated to confirm the findings. There are therapies that, decades later, still have had no follow-up, and the Longevity Research Institute would like to change this situation.

To that end, it will be engaged in grant writing to obtain funds so that researchers studying aging will be able to conduct lifespan studies in mice and rats. The Longevity Research Institute also plans to commission its own studies and contract research organizations to carry them out.

It has a long list of promising interventions and is considering becoming involved with carboxyfullerenes, epithalamin, and stem cell transplants, for example. It is also interested in testing combinations of therapies to see if they have synergistic effects.

As translational research on aging is really a new, uncharted territory, the Institute is working with the Interventions Testing Program and METRICS to design reproducible animal studies. As part of that process, it will be testing genetically heterogeneous animals and using blind, randomized studies to reduce bias. A blind experiment is an experiment in which information about the test is hidden from participants, to reduce or eliminate bias, until after a trial outcome is known.

Best practices and transparency

Establishing best practices and protocol for translational aging research is a top priority here, and its work could help set the stage for future translational efforts. If superbly designed research protocols can be designed and made accessible to everyone, then they could be a real help in standardizing aging research and ensuring that the quality of results is the best it can be.

As part of its commitment to transparency and knowledge sharing, a condition of funding projects is that all experimental data will be made freely available to the public, as will pre-registration of experimental designs. The Institute will further protect this open science initiative by using blockchain technology to make immutable, publicly accessible records of everything it does.

We had the opportunity to talk with Sarah Constantin, Ph.D. and one of the key figures at the Longevity Research Institute, about their work. Sarah is a data scientist specializing in machine learning.

Your group believes that we need to conduct lifespan studies in mice in order to confirm that something might translate. However, some researchers believe that using multiple biomarkers of aging allows them to project, within a reasonable margin of error, changes to potential lifespan. This is becoming more relevant as the accuracy of biomarkers, and the use of comprehensive biomarker panels, becomes more commonplace. How do you respond to this?

There’s some very interesting stuff going on with biomarkers of aging.  We’re able to predict mortality with AUCs of 0.8-0.9, which is quite good, with aging biomarkers, including things like blood panels of inflammatory and metabolic markers, DNA methylation, and phenotypic markers such as BMI and frailty. Some of these biomarkers are things we’re planning to measure in our animal studies, and they should give us interim results on whether the interventions we’re testing affect the predictors of aging. I still believe that we can be most confident in whether a treatment promotes longevity when we’ve tracked its effects throughout an organism’s lifespan. We do know of examples (such as calorie restriction in primates) in which it’s equivocal whether the treatment extends lifespan but it clearly improves age-related biomarkers, and you have to do a lifespan study to distinguish those cases.

Advances in deep learning and systems pharmacology are allowing us to project interactions and potential therapies far more efficiently than ever before. What are your thoughts on these approaches, and will you be looking to use them in your work?

The deep learning and systems pharmacology approaches are actually where I started in biotech; I did machine learning at Recursion Pharmaceuticals, which is taking those approaches for doing phenotypic screens for genetic disease treatments. I think they’re really useful for drug discovery, at the beginning of the pipeline, where they can enable you to search a wider space of drug candidates. At LRI, we’re starting all the way at the other end of the pipeline, with drugs that have already been tested and shown promise in vivo. However, once we make some progress on those, then yes, it could make sense to start doing some of these machine learning-enabled approaches.

What is the ideal mouse strain for aging research, particularly lifespan studies, in your view?

Well, the Interventions Testing Program at the National Institute of Aging is using three-way heterozygous mouse crosses, which I think is the ideal. A single inbred strain of mouse doesn’t have much genetic diversity, so often what you’re testing is the effect of a treatment on that particular strain of mouse, and the results won’t transfer to another strain.

The use of progeria mice is common in aging research due to the shorter study time, but these models are often criticized as not being representative of true aging; what are your thoughts on the prevalence of progeria mice in aging research, and are they a relevant model for what we are trying to achieve?

I think progeria mice are an imperfect proxy. There are a lot of different kinds of progeria, and they exhibit some but not all of the typical symptoms of natural aging.  I’d have more confidence in studies done on aged mice than progeric mice.

We see that you have a strong commitment to ensuring public access to scientific knowledge. What inspired you to make such a wonderful and strong commitment to open science?

Well, coming from a data science background, I’m hyper-aware of how easy it is to fool yourself with data.  You can massage anything into a spurious result if you test enough hypotheses and pick your subgroups artfully. Really, the best way to guard against that is to share the raw data so that people can run their own analyses. Making science more open is how you make it more trustworthy.

Is there a publically viewable list of the targets that you are interested in testing?

The list is still evolving, but some of the first things we’re looking into testing are carboxyfullerenes, which seem to have neuroprotective and life-extending effects, and epithalamin, which is a pineal gland-derived peptide that’s been reported to extend lifespan and even reduce human mortality. Both of these are sort of in the sweet spot of not being the subject of that much research to date, but what there is is very promising, so the value of information is high.

What is likely to be your first target for studies, and what is the rationale behind your choice?

I think people should know that there’s a lot of low-hanging fruit in aging research — treatments that we have reason to believe might work but that we’d still have to test. The misperceptions are either that life extension is so speculative that we’ll never get there or that we already know how to do it and you just have to take the right supplements to live forever. I think the reality is that we’ll have to do a lot of experimental work, but it’s highly possible that, in time, we might find something that extends healthy lifespan in humans.

We would like to thank Sarah for taking the time to do this interview with us, and we look forward to seeing her team’s progress in the near future.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by at the Life Extension Advocacy Foundation (LEAF) on July 19, 2018. In this article, Mr. Hill does an excellent job explaining why the lack of the definition of aging as a disease under the FDA is not so bad as is sometimes feared. Personally, I do not agree with this. Relying on off-label use is not a good idea because that is much slower of a process than doctors quickly seeing that a drug has FDA approval. Once the FDA considers aging as a disease, pharmaceutical companies will quickly enter this arena and make increasingly better drugs. Mr. Hill makes some excellent points, though, and I highly recommend this article. 

~ Bobby Ridge, Assistant Editor, June 29, 2019

A common concern in the community is that the FDA, the EMA, and other bodies, such as WHO, do not classify aging as a disease and that this poses a problem for developing therapies that target aging. However, this is not really as serious an issue as some people would suggest; today, we will have a look at why that is.

Why this will not stop progress

Aging is a variety of distinct processes, damages, and errors; therefore, simply treating aging in clinical terms is not a viable endpoint. For a clinical trial to be conducted, it requires a verifiable indication, and aging is too general for the FDA and EMA to classify it as a disease.

It also is not a major challenge for damage repair-based approaches, such as those proposed by SENS and the Hallmarks of Aging, as these approaches are not focused on an all-in-one therapy with the indication of “aging”. They are based on a strategy of dividing damages into manageable groups and developing a suite of rejuvenation therapies that addresses each of them.

No single therapy will reverse or halt all of the aging processes when used alone, nor will it prevent all age-related diseases that accompany them. So, to have aging as an indication in any clinical trial would be pointless for any damage repair therapy.

Researchers are free to target aging processes

That said, researchers are very well aware that the processes of aging, which lead to the familiar diseases of aging, are a problem, and this is where the focus lies. There has been considerable effort to classify these processes and precursors of pathology as diseases themselves.

A prime example is the inclusion of sarcopenia (frailty and muscle loss) in the World Health Organization International Classification of Diseases (ICD) a few years ago thanks to lobbying by members of our community. Adding more general codes to the ICD that include these aging processes and precursors is an ideal solution, as it could potentially make it easier to organize trials and develop drugs that target the aging processes.

Back in June 2018, the World Health Organization released the new International Classification of Diseases (ICD-11). The previous version, ICD-10, was published in 1983, and the new ICD-11 will likely be the standard for years to come. The new ICD-11 now includes the extension code “Ageing-Related” (XT9T) for age-related diseases, and this should go a long way towards making focusing on aging easier for future drugs and therapies. Again, this is thanks to work by members of our community, who have spent countless hours researching and pushing for change.

Most aging hallmarks are very clearly linked to specific age-related diseases, such as beta-amyloid protein and malformed tau in Alzheimer’s, lysosomal aggregates in foam cells in atherosclerosis, and alpha-synuclein in Parkinson’s disease. Companies are perfectly welcome to target these aging processes directly, and indeed more and more researchers and big institutions are doing just that in order to treat age-related diseases.

Therefore, not classifying aging itself as a disease poses few barriers to developing therapies that address aging; it’s simply a case of working within the existing framework. UNITY Biotechnology is a prime example; this company is targeting senescent cells and applying its method to multiple age-related diseases; as everyone gets senescent cells, these therapies will be broadly applicable once they become available, and off-label use is likely to expand rapidly.

Also, rejuvenation therapies could, at first, be licensed as treatments for genetic disorders, even though the root cause of the pathology underlying those diseases is not aging. An example of this is the inherited mitochondrial disorders, known as mitochondriopathies, many of which are caused by mutations in the mitochondrial DNA (mtDNA). While these mutations are inherited and are not the result of age-related, deleterious damage to the mtDNA, the same repair-based approach can be applied: the allotopic expression of the protein in the nucleus, as proposed by MitoSENS, could potentially be used to repair the mtDNA allowing normal cellular function to resume.

The majority of damage repair therapies, if not all, could be developed as therapies for diseases with accepted indications and verifiable endpoints, which should satisfy bodies such as the FDA and EMA. Therefore, whether regulatory agencies perceive aging as a disease or not is of no consequence to the development of rejuvenation biotechnologies that address the aging processes.

This does not mean regulatory changes are not needed

Even though classifying aging as a disease is unnecessary, significant reform in the regulatory system is still needed in order to encourage investors and companies to put the time and money into researching and developing rejuvenation therapies.

One area in need of reform is the establishment of aging biomarkers, which indicate the repair or removal of age-related damage, as acceptable endpoints for rejuvenation therapies. Studies that use these biomarkers would also need to include long-term follow-up studies to ascertain the effects of a therapy over a longer period of time.

This would deviate from regulators’ normal requirements that therapies have to prove an effect on hard outcomes to be approved. In an ideal situation, patients should get rejuvenation therapies long before they are in immediate danger and once diseases have manifested, but this makes trials more time consuming and more costly to run.

However, back in February 2018, the FDA published a new guidance document detailing how early-stage Alzheimer’s patients might be identified, which, if accepted, would represent a significant change in policy and a step in the right direction. The document suggests that the results of imaging tests or suitable biomarkers could be enough to consider Stage 1 Alzheimer’s patients as suitable subjects for clinical trials.

This is a positive move as it means that therapies can be tested on people in the very early stages of Alzheimer’s rather than on those who have already suffered considerable if not irreparable damage to the brain, damage that no therapy could hope to address alone. This could mean that these early-stage patients could enroll in a clinical trial and take a therapy that could potentially prevent the disease from ever progressing further or reaching the point where cognitive decline begins.

In the case of repair-based therapies, it would then be a case of demonstrating that the early stages of Alzheimer’s disease were improved via the removal or repair of the underlying age-related damage, and suitable biomarkers would show this.

Moving with the times

Another area where regulatory bodies have struggled is keeping up with the rapid march of technology and medicine. Technologies such as gene therapies have struggled to gain traction due to an antiquated regulatory framework struggling to cope with them. Thankfully, this is also being acknowledged, and the regenerative medicine advanced therapies (RMAT) framework published earlier this year seeks to address this issue and make large-scale changes to how its regenerative medicine policy framework operates as a whole.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

While the FDA created these new guidelines, we joined forces with the Niskanen Center to submit comments to the agency so that it would hear the voice of our community.

Conclusion

Aging not being classified as a disease by the FDA, EMA, etc. is not a major issue; the real need is for policy changes that make developing drugs and therapies that target the aging processes easier and more financially viable. It is good that changes are being made to current frameworks and that progress will almost certainly continue in these areas.

Meanwhile, we can continue to support the development of repair-based approaches to aging knowing that such therapies, if they work, will be approved even in the current regulatory landscape.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Popular Reactions to Life Extension – Article by Nicola Bagalà

Popular Reactions to Life Extension – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Nicola Bagalà, originally published by our allies at the Life Extension Advocacy Foundation (LEAF ) on May 31st, 2018. In this article, Mr. Bagalà examines two studies from 2009, in which researchers interviewed members of the public regarding their opinions of life-extension research. This is an excellent read if you want to peer into how people in the past felt about life extension. 

~ Bobby Ridge, Assistant Editor, June 28, 2019

Two papers by Partridge et al [1, 2], both published in 2009, provide the somewhat rare opportunity to examine some concerns about life extension as formulated by actual people, rather than their general, more abstract forms.

As highlighted in the studies, research on the public’s perception of life extension science has been very much neglected; this, in turn, has made it harder to identify the misconceptions and incorrect information fueling some common concerns about life extension and made it even harder to address those very concerns. Needless to say, the more that the public views life extension negatively, the less supportive that it will probably be, which is bad news for researchers.

The papers present the results of several interviews, conducted either in person or on the phone, aimed at understanding what ethical concerns the interviewees had about life extension and what implications they thought extended human lifespans would have for themselves and for society. The research was conducted on a sample of the Australian population only, but the issues they raised were entirely representative of a typical discussion about life extension. In both studies, the interviewees were presented with the general premise of possibly slowing down aging and the onset of age-related diseases in order to greatly extend human healthy lifespan.

We’ll be taking a look at specific claims made or sentiments expressed by different interviewees in both studies.

Nature (doesn’t) know best

A common assumption is that nature knows best and interventions to slow down or reverse aging equal tampering with it, which is bad in its own right and therefore shouldn’t be done. This position is apparent in the following quotes from the studies:

“It seems totally unnatural. It seems to be upsetting the natural sequence of things. […] But I think doubling life would be… I don’t like it at all.”

“[…] it’s just not natural to live to 150.”

Quite frankly, this is the kind of teaching you would expect to find in an episode of “The Smurfs”, in which Mother Nature is a sweet old lady with a magic wand and has designed the world to work in a certain way for everyone’s good. However, nature is really just a label used to indicate many things—the interactions between fundamental particles, animal behavior, the intricacies of biochemistry, green foliage, and black holes. No one sat down and decided how long each species should live, and most definitely not for anyone’s good.

Counterexamples of natural things that are bad for you and “unnatural” things that are good for you are plentiful, but we’re not going into counterarguments and confutations; what is interesting to note is that the naturalness argument is presented without further justification: it’s unnatural, hence it’s bad. The interviewees themselves don’t seem to know why it’s bad. It’s rather dangerous to assume that nature knows best when, in fact, it knows nothing at all. Nature does all it does rather well—who wouldn’t, after billions of years of practice—but that’s not necessarily what is best for you.

Another interesting claim is that extending our lifespans would make us less human—as if living around 80 or 90 were a defining quality of humanity:

“To change lifespan that much just seems like, I don’t know, we’re not human anymore… Think of all the intervention we’d need… we’d be counteracting everything about us to make us live longer.”

“[…] it’s kind of inhuman to live a long time, as we are not made that way […]”

It’s honestly difficult to imagine why a lifespan change from around 80 to around 150 would make us any less human than the one from about 40 to about 80 did. However, the covert assumption here might be that extending lifespan would necessarily require radical alterations that would turn us into something we don’t like—a rather stale teaching that has been reiterated, unproven and unchallenged time and again in all manner of fiction, so it wouldn’t be surprising if it had made its way into people’s most deeply held beliefs.

Some interviewees expressed the conviction that curing disease and extending lifespan are fundamentally different:

“There’s a difference between just treating an injury or an illness compared to ‘I’m going to break natural bounds and extend my life’.”

“I don’t think life extension, in the sense of strong life extension, is a necessary thing. Whereas a lot of other aspects of medicine involve fixing things to enable people to live a normal life in a regular lifespan.”

The misconception that might be behind this is that there’s a “right” kind of death—death by old age—whereas other kinds of “early” death, however they may happen, are “bad” kinds of death in that they’re not the way things are supposed to go. It’s almost as if there were a belief that death is scheduled to happen to us irrespective of our health at some point around age 80 or so; death “ahead of schedule” is considered a tragedy, and postponing your “scheduled death” is considered “breaking natural bounds”.

However, this is at odds with everything we know about the functioning of the human body. Medicine is not meant to fix things so that you live a normal life in a regular lifespan; medicine is meant to fix things so that you retain your health and thus continue living. That’s all there is to it. Nowhere is it said that medicine works or should work only within the boundaries of a “regular lifespan”; the only reason why the current “regular” lifespan is of about 80 years is that, thus far, we haven’t been able to cure the ailments that manifest at that age, in pretty much the same way that 300 years ago, we didn’t know how to cure infectious diseases. This interviewee summed it up rather well:

“I don’t know how to separate the rate of aging though from a disease. I don’t know what the difference would be if you took away all of the diseases, if you took away all of the things that could cause heart failure, cancer and all of those sorts of things. I see them the same as aging.”

The authors of the papers reiterated many times how interviewees were favorable to what they perceived as therapies to cure diseases and against all that they perceived as an enhancement; for some reason, extending lifespan was perceived as the latter, rather than merely the obvious consequence of curing the diseases of old age. In this sense, rejuvenation therapies are no more an “enhancement” than any therapy that prevents or cures life-threatening diseases earlier on in life. This point can never be stressed enough.

Discriminations and impositions  

Another extremely common concern is the ill-famed spectre of unequal access to rejuvenation biotechnology, summed up by these two quotes from the studies:

“I don’t think any good will come out of it. It would be beneficial to only one class, supporting only one social class. In a way, we will unbalance the powers.”

“We end up with this society where the poor live their brief little lives and then you know… The rich live forever and have time to accumulate vast resources and there is never any way to cross the divide.”

If you are interested in more detailed counterarguments, you will find them here and here; what is most interesting to note in this venue is the fatalistic attitude of this stance. Not only did interviewees—along with many more people—assume that the dystopian scenario they presented will certainly occur; they didn’t seem to think that measures could be taken to prevent it or even just mitigate its effects or shorten its duration. They didn’t seem to think that the benefits of an aging-free world—which several interviewees acknowledged and which you can read about here, here, and here—might be worth the effort of looking into ways to prevent or mitigate any potential problems, such as inequality of access.

The same can be said of two more common concerns: overpopulation and lack of resources. The answers of the interviewees betrayed the assumption that the problem is inevitable and impossible to even alleviate, as if our technological development had already reached a peak and further innovation in terms of resource production and management were utterly out of the question, neglecting the obvious precedents in this regard—the Malthusian catastrophe has been predicted time and again and always failed to materialize; supporting a world population of even just a billion would have seemed impossible with the technology of 300 years ago, yet present-day technology allows us to cope with seven billion people—not perfectly, but we’re on our way there.

Worse still, interviewees didn’t seem to realize the even more obvious fact that, assuming that rejuvenation would be only for the rich, banning it, as some suggested, would do exactly nothing to narrow the rich-poor divide; at best, it would prevent it from getting larger. However, nobody benefits from a technology not existing, let alone the poor. Imagine if, back in the day when sewers to separate waste from water were first invented, someone suggested that we don’t build sewers anywhere at all because some areas could end up being unjustly left out. Making sure that sewers reach everywhere, even if it takes a long while before they actually do, is a much better idea than having water mixed with waste everywhere forever.

Whether or not the rich live forever is rather inconsequential for the poor, especially as long as they don’t even have the basics covered—even though some people think that the poor somehow find comfort in thinking that one day the rich will die of aging if nothing else gets them first. The idea of relishing someone else’s death, regardless of the circumstances, is so appalling that it’s paradoxical how this whole argument is often called one of “ethics”.

Another interesting concern related to financial possibilities is that if you live longer, you need to support yourself for longer; some interviewees were afraid that the quality of their extended life wouldn’t be good, because their finances might not be good either. This is another scenario where utter pessimism somehow managed to take the place of common sense. It’s very sensible to be afraid of a life of poverty, but if you found yourself so poor at age 30 that your quality of life suffered significantly, the odds are that you’d do your best to try to lift yourself out of poverty well before even contemplating death as a liberation. If you found yourself poor at, say, age 120, and assuming that you were perfectly healthy because of the very life-extension technologies that allowed you to reach that age, why should this case be any different?

At least for some interviewees, the difference might be that they found the prospect of having to work for longer as a “significant downside to taking life-extension pills”. To put it bluntly, they’d consider dying as an alternative to working for longer, which hints that the problem might lie in the jobs they do rather than in how long their lives are.

More concerns related to access to the therapy, rather the opposite of each other, were expressed by interviewees afraid that they might be coerced into using life extension or that life extension users might end up having to watch as their friends and relatives who refuse these treatments slowly wither and die.

For the first concern, this might betray a lack of understanding of what life extension is, because it’s hard to imagine how anyone could worry about being coerced into being healthy; as for the second one, it’s surprising how these interviewees didn’t notice that their fears are already taking place here and now. The old people of today need to get used to the fact that their lifelong friends and companions keep dying around them, and to add insult to injury, their own health is also going critical. Granted, if you yourself die of old age at some point, you won’t have to continue witnessing the death of your loved ones; however, this is pretty much equivalent to curing the disease by killing the patient.

The Real Problems™ are others

The argument that there are higher-priority problems than aging was also among those touched upon by the interviewees:

“I don’t see the point in developing something else at great expense that may not be available to everybody, when money could be channeled towards getting the basics of what people would have a right to them now so that they’re not starving and dying.”

“What’s the point of me living to 150 if six-year-olds are going blind and needing kidney transplants because they’ve got diabetes?”

Appeal to worse problems is very much the fallacy being committed here; once more, the truly important thing is assumed to be something else. For some reason, the interviewees appeared blind to the possibility that the pursuit of rejuvenation might not necessarily be incompatible with that of alleviating poverty, etc; their unproven assumption seems to be that, with the resources available, it is absolutely impossible to achieve both. Also, interviewees didn’t seem to value the life of elderly people as much as that of people who are in danger of death from other causes, such as starvation or health problems at a younger age. In both cases, somebody’s life is at stake, and yet it appears that the life of someone who has already been around for several decades is less worth saving—even though, given the premise of the study, this life wouldn’t end in a handful of years spent in ill health but rather in a far longer period spent in good health.

For some other interviewees, “medicine” was ironically a more important priority than life extension—as if there were any difference between the two. In their minds, the risk is sometimes that research funds could be diverted away from more pressing medical needs. The fact that some of them failed to realize the connection between aging and disease is apparent from this quote:

“They’ve got to look at this [life extension] one hundred years in the future when they’ve got all the diseases sorted out.”

It appears this interviewee expected that, in a hundred years, when all diseases will have been sorted out, people in their 80s will still drop dead for no apparent reason; only then should we start looking into how to extend life. This betrays a serious lack of understanding of the deep connection between healthspan and lifespan, and it is something that advocates of life extension need to make extremely clear. Indeed, the idea that being old equals being sick is (rightfully) so ingrained in our minds that, even though the researchers had clearly stated that life extension means being healthy for longer, some interviewees still struggled to comprehend this and were concerned about how physically and mentally healthy they could be nearing 150 years of age.

Yet some others understood all too well how life extension implies retaining your health during old age, and this was their very concern:

“You’d miss out on that aspect of what it is to be an older person… I think that there’s natural progressions [sic] in growth and that’s why I don’t think you can do it without aging in some ways because you’re not actually physically or whatever in that situation. Intellectually it’s not the same as experience of it. So it’s a whole barraging process that could actually stunt our development; the depth of who we are as human beings.”

This is by far the weirdest concern you’re likely to run into—it’s like saying you shouldn’t cure cancer if you get it, lest missing out on what it is to be an oncological patient. Not all experiences are worth having; from my middle school days, I recall how being hit by a basketball kicked straight into my groin at point-blank range was something I would gladly have done without, and the lack of this experience would hardly have stunted my development—if anything, my early teenage development risked being arrested altogether because of this very experience.

What’s absolutely puzzling about this quote is the kind of development we’re even talking about. A person in his or her 80s has been developing for quite some time already, and intellectually, his or her experience of life is hardly going to be improved by cancer, diabetes, or Alzheimer’s. Besides, whatever experience you might gain by going through the ordeal of age-related diseases, you’re not going to take it with you for very long, so it’s unclear how it would benefit you in the first place. Possibly, the point this person was trying to make might be that you need to experience bad things to learn that they’re bad, but this is true only to an extent. After a certain point in your development, you can extrapolate how good or bad something is without actually experiencing it—believe me, I didn’t need to be hit by that basketball to know that it would have hurt very much.

Old inside

Some interviewees were worried that, rejuvenation or not, an old person always stays old mentally; they feared that they might end up being “an old person in a young person’s world”. This suggests that some people may have internalized the stereotype of old people as being out of touch with the world simply by virtue of being old when, in fact, their health plays a central role in how able they are to stay connected with the rest of us. Old people in today’s collective imagination are confused by computers and technology, less educated than young people, and less open to change and novelty. This depiction is partly correct due to the exceptionally large generational gap between our generation and our grandparents’—in some cases, even our parents’. It is conceivable that, having been exposed to this representation of the elderly our whole lives, some of us conclude that we, too, will be like this in our old age, as if this way of being were a product of the age itself rather than the sociocultural context in which we spent our lives.

Gerontocratic scenarios

Some interviewees showed another typical concern—that the older, rejuvenated people might just keep consolidating their wealth and power, shutting out younger people from opportunities. The long-lived elderly, they feared, might also hinder generational turnover and the emergence of new ideas.

An important factor that interviewees didn’t seem to think about is that being part of a new generation doesn’t automatically make you able to have new or better ideas. However young or smart you may be, you will have a hard time being much of an innovator if you don’t have access to adequate education and aren’t encouraged to engage in open, creative thought. Creativity and new ideas need these elements to thrive; they don’t just magically appear with the turn of every generation. Naturally, the gradual loss of brain plasticity as we age may make it harder for older people to be innovative, but if this problem can be fixed by sufficiently comprehensive rejuvenation therapies, then there’s no reason to assume that long-lived elderly will be a drag on progress.

As for the concern of a gerontocratic elite taking over as a consequence of rejuvenation, one should notice above all that it is typically expressed in such a vague fashion that it is impossible to falsify. Nothing absolutely prevents any dystopia from ever coming into being; in order to be able to tell whether rejuvenation will lead to a gerontocracy in 300 years, we would need information on the socioeconomic and technological context of the coming three centuries. Without it, this concern is pure fear-driven speculation. Its profound appeal to people’s sense of justice is probably what allows it to bypass rational scrutiny and appear as a valid objection despite the lack of evidence.

Ethics

According to the study’s authors, some participants defined “being ethical” as “thinking beyond one’s own life”; in their view, life extension didn’t fulfill this criterion and was an unethical, selfish pursuit:

“Ultimately, I don’t know if everyone should be doing it, but you know how you have those selfish desires?”

Life extension is about eliminating useless suffering just as much as the rest of medicine. Doctors saving people from deadly diseases are thinking well beyond their own lives, and it’s unclear why this wouldn’t be the case if they saved lives by administering rejuvenation treatments.

Other interviewees were instead clear that life extension is perfectly ethical:

“I can’t see an ethical issue. There’s no more an ethical issue than medicine being able to cope with disease. Is there an ethical issue in that? They’re prolonging life now with immunization and even heart transplants. People have come to accept this now.”

Others suggested that opposing life extension is unethical, because

“[…] you’re killing people. If you have the world where you can take an action where you do make someone live longer, or you can take the action that you can say ‘live shorter’, which is a take no action at all, that’s still an action. Then you’re killing them, you caused their death. Your action of not doing anything causes their death. So it’s unethical to not do this.”

The belief that life extension is a selfish pursuit was further stressed in other interviews:

“But then you’ve got all the societal impacts like cost and population growth. There are so many different things that nobody really thinks about when they’re thinking ‘Oh, I could live to 200, that sounds great.’”

“They [people who want life extension for themselves] are not thinking about anyone else.”

Once more, interviewees took the dire consequences they imagined for granted. As the study authors themselves pointed out, to some interviewees, the potential downsides of life extension appeared to be such inescapable certainties that they were not interested in the possibility at all. This might explain the belief that life extensionists don’t think about anyone else; seeing the “selfish” benefit of prolonging your healthy lifespan is easy, but it’s far harder to see that the alleged societal costs of it are not as set in stone as one might think.

One last, interesting position on the selfishness of life extension was expressed by the following interviewee:

“I don’t think there’d be any great social benefits in me living to 300… It’s all about greed and selfish purposes I suppose for why you would try to prolong your life. Ultimately, I don’t think it would impact the world in a positive way. It’s fair to say I wouldn’t be doing it for social reasons.”

It is again apparent that what really matters is not individual people’s lives—only what is good for society matters. However, society has no point if not that of serving the individuals of which it is comprised; if society asks its members to die for society’s sake, it is not doing them a very good service.

In reality, human society doesn’t have much to gain from shorter lifespans for its members, and its functioning is unlikely to be hindered by life extension. Aspects of it will certainly require rethinking, but it is indeed constant rethinking of how society works that allows us to improve it.

Fear of death

To some interviewees, fear of death wasn’t a good enough reason to justify life extension:

“Yes, it’s selfish… but it depends on what reasons you want to do it… they shouldn’t be able to extend their life just because they’re afraid of dying. It should be for a greater cause.”

The idea that only a “greater cause” than fearing for your own life legitimizes use of life extension is reminiscent of the old ideal that your life only matters as long as it serves the rest of society in some way. (The “greater cause” can’t be much else than serving others, if life extension for your own sake is not allowed.)

The ancient idea that death must not be feared—in part to exorcise the fear, very strong indeed, that it instills, and in part because a fearless army was in the best interest of the rulers of the past—has made its way into our modern time and is still alive and well. Being afraid of death is still mostly seen as a shameful thing, and many people still proudly proclaim that they don’t fear it; they’re much more afraid of the horrors that, allegedly, are an inevitable consequence of longer, healthier lives. Among the study participants who acknowledged the benefits of life extension, very few mentioned allaying the fear of death as a good reason; it wouldn’t be surprising in the least if they didn’t because they thought that it would be shameful to do otherwise.

Still, if we really weren’t afraid of death, our languages wouldn’t be full of all manner of euphemisms, edulcorations, and embellishments for it; religions wouldn’t all be hinging on overcoming death through resurrection, reincarnation, and the like; we wouldn’t have come up with any of the technologies that allow us to save lives in the most desperate cases; and we wouldn’t consider it heroic to save other people’s lives even at the cost of endangering our own.

Conclusion

Some of the most common concerns involving life extension are often taken to be inevitable consequences of it; from what can be seen in the two studies, interviewees never doubted that their fears would materialize if life extension were ever achieved. It would be interesting, as well as useful for more effective advocacy, to establish whether this happens because of a lack of relevant knowledge, the psychological effects of our perception of aging, or a combination of both.

Literature

[1] Partridge, B., Underwood, M., Lucke, J., Bartlett, H., & Hall, W. (2009). Ethical concerns in the community about technologies to extend human life span. The American Journal of Bioethics, 9(12), 68-76.

[2] Partridge, B., Lucke, J., Bartlett, H., & Hall, W. (2009). Ethical, social, and personal implications of extended human lifespan identified by members of the public. Rejuvenation research, 12(5), 351-357.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. in mathematics; an amateur programmer; a hobbyist at novel writing, piano and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.

Citi Lists Anti-Aging Medicines in Top 10 Disruptive Technologies – Article by Steve Hill

Citi Lists Anti-Aging Medicines in Top 10 Disruptive Technologies – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on August 30th, 2018. In this article, Mr. Hill presents Citi’s latest disruptive innovation publication, in which anti-aging medicine is #2 on the list! This is one more example, out of the myriad of examples, of how big of an impact this field is making. One of the reasons Citi considers the development of anti-aging medicines to have a high impact is the fact that “U.S. health spending, which increases significantly with age in concordance with age-related diseases, is expected to exceed ~20% of U.S. gross domestic product (GDP) by 2025.” 

~Bobby Ridge, Assistant Editor, June 27, 2019

Citi has produced another of its Disruptive Innovations publications, which takes a look at what it considers to be the top ten disruptive technologies. It is a sign of the changing times that anti-aging medicines are number 2 in its list.

1. All-Solid-State Batteries
2. Anti-Aging Medicines
3. Autonomous Vehicle Networks
4. Big Data & Healthcare
5. Dynamic Spectrum Access
6. eSports
7. 5G Technology
8. Floating Offshore Wind Farms
9. Real Estate Market Disruptors
10. Smart Voice-Activated Assistants

What was considered fringe science a decade ago is now rapidly becoming a mainstream industry. Our understanding of aging has advanced quickly in the last 10 years, and the tools and innovations seem to come more quickly with each passing year. A variety of therapies that target different aging processes are in development, and some are at fairly advanced stages; if you are interested in their progress, check out the Rejuvenation Roadmap.

Advancing Health by Turning Back Time

The legend of the restorative powers of the Fountain of Youth has fascinated human civilization throughout the generations, dating all the way back to the Greeks (e.g., Herodotus). Other hypothetical conduits for a return to a state of youthfulness (e.g. the Philosopher’s Stone) have featured prominently throughout human civilization as alluring, but equally elusive. Fast forward to 2018, and very recent cutting-edge scientific breakthroughs may, at long last, fundamentally explain why we age. This rapid scientific progress could spawn FDA-approved therapeutics potentially in the next decade, with the primary goal of keeping us younger and alive for longer.

Today, the anti-aging market, while huge (~$200 billion globally), is largely restricted to non-therapeutics (cosmetic products and procedures). At the same time, U.S. health spending, which increases significantly with age in concordance with age-related diseases (see Figure 8), is expected to exceed ~20% of U.S. gross domestic product (GDP) by 2025. Thus, with scientific breakthroughs emerging this decade on the cellular origins of why the tissues in our body’s age, novel anti-aging medicines may become one of the next big disruptions in the healthcare market.

Senolytics are the main focus here, which is logical given that, of all the therapies being developed to combat aging, they are the farthest along in the pipeline. These analysts suggest that we could see senolytics arrive by 2023; while these drugs are only part of the full suite of therapies required to bring aging under medical control, it is likely that we will see senolytics and, perhaps, a few other therapies arrive at that time.

First Senolytic Therapy Could Be Approved by 2023

The first senolytic therapy in clinical trials is a compound by Unity, UBX0101, which is a small-molecule drug that functions by inducing apoptosis (i.e., programmed cell death), specifically in senescent cells. The company is first testing UBX0101 locally in patients with moderate osteoarthritis of the knee, which is a substantially large market (~17 million patients). Initial proof-of-concept data from the Phase 1 trial are expected in the first quarter of 2019. If successful in later clinical development through Phase 3, UBX0101 could become commercially available by 2023.

While speculative given the novelty of the senolytic therapeutic strategy, a successful therapeutic that could resolve osteoarthritic knees and return knee tissue to a more youthful state could have a negative impact on the knee-replacement surgery market (currently projected to grow to >3 million knee replacements per year by 2030). Because other senolytics are being developed for multiple
ophthalmologic (wet AMD, glaucoma, diabetic retinopathy) and pulmonary (COPD, idiopathic pulmonary disease) indications, within the next ~10–20 years patients with a range of age-related diseases may experience a decreased need for therapies now considered standard of care.

UNITY, Siwa, and Oisin are all mentioned in the report. and it is worth having a read, as the section about aging is fairly large and detailed and takes a look at past and present attempts to combat age-related diseases by targeting the aging processes directly.

Conclusion

It is beyond question that progress and interest in the field is growing quickly, and with some therapies now entering human trials, we could be close to a societal tipping point at which more people start to take notice of the potential of new medical approaches. There is a long way to go before we can end age-related diseases, but the tide has turned.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity, created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

 

Nicola Bagalà Interviews Reason of the Fight Aging! Blog and Repair Biotechnologies

Nicola Bagalà Interviews Reason of the Fight Aging! Blog and Repair Biotechnologies

Reason
Nicola Bagalà


Editor’s note: The U.S. Transhumanist Party features this article by our guest Nicola Bagalà, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on May 14th, 2018. In this article, Mr. Bagalà interviews Reason, an activist who has been helping scientists to cure age-related diseases and posting in-depth commentary on a blog dating back to the 2000s. Reason has helped multiple fundraisers and contributed much more to the progress of life-extension research. The topics of the interview range from a quick biography of Reason’s involvement in fighting age-related diseases, to a discussion of when aging will be defined as a disease by the FDA. The interview also covers Reason’s new company, called Repair Biotechnologies.

~Bobby Ridge, Assistant Editor, June 25, 2019

Most people interested in rejuvenation and life extension are familiar with Fight Aging!, one of the very first rejuvenation advocacy blogs dating back all the way to the early 2000s; if you’re one of them, then you certainly are familiar with Reason, the man behind FA!.

Over the years, Reason has been a patient yet relentless advocate, acting not only as an information provider for the public but also helping out innumerable organizations and companies in the field of rejuvenation biotechnology in financial and other ways. Back in the day when SRF didn’t exist yet, Reason was a volunteer for Methuselah Foundation; eventually, he helped fund companies such as Oisìn Biotechnologies, CellAge, and LysoCLEAR; and, earlier this month, Reason and Bill Cherman co-founded Repair Biotechnologies, a company focused on gene therapy for rejuvenation, as announced on FA!.

Bill Cherman is an investor in the rejuvenation community who, just like Reason, has contributed to development of many ventures in the field. He is a holder of a gold medal in the Brazilian Mathematics Olympiad, a BA in economics, and a candidate in the Master of Biotechnology Enterprise and Entrepreneurship program at Johns Hopkins. He founded Front Seat Capital, a venture capital firm looking to invest in startups with the potential to change the world.

Repair Biotechnologies, which is presently looking for a Chief Science Officer, will kickstart its activities with a project on thymic regeneration in partnership with Ichor Therapeutics—the creators of LysoCLEAR, Antoxerene, and RecombiPure. The goal of the company, as you can imagine, is to shorten the journey of rejuvenation therapies from the lab to the clinic.

It is extremely heartening to see more and more rejuvenation-focused companies and organizations sprouting and building up to the turning point when this emerging field of science will cease being fringe and become a hot topic not only in the relatively small circle of biogerontology (where it has been one for a while now) but also in business and public discourse. We’re very grateful to Reason and Bill for taking us yet another step closer to the finish line and for answering our questions.

We’d like to ask some details of your story as a rejuvenation advocate. When and under what circumstances did it become clear to you that aging is a problem?

While it would be delightful to claim that I am a rational entity who came to that conclusion through utilitarian thought, in fact, it was more of a bolt from the blue. For no apparent reason, it suddenly came to me one evening that I didn’t want to die – and not in the academic way that most people hold that conviction but a deep, visceral, adrenaline-laden realization of the sort in which one accepts immediately that something important in life has been done and determined, a corner turned. Before that happened, I was no more than passingly interested in aging as a topic, but afterwards… well, I woke up. Of course, that was a long time ago now, far prior to my present understanding of what is plausible and possible, and realization on its own achieves nothing. It took years to learn enough to progress any sort of understanding as to how a non-life-scientist could make a difference.

We have noticed that there has been a sea change in both progress and enthusiasm from the academic community for rejuvenation biotechnology and targeting aging directly to prevent age-related diseases. Have you observed a similar rise in support, and what factors, if any, do you think are driving this?

I think that these things progress in cycles, based on the timescale of human collaboration. It takes a few years to go from desire to setting up an organization, a few years for the organization to get somewhere, and a few years for others to be inspired to their ventures by the organization. Bootstrapping only looks smooth in hindsight. We have been transitioning from one business cycle to another these past few years, which looks like a big leap in enthusiasm as it occurs, but the roots of this were set down five to ten years ago. I would say those roots included the final tipping point studies for senolytics, the spin-off of the SENS Research Foundation from the Methuselah Foundation, the injection of funding for SENS around then, and a number of other, related items.

It we look around today, a bigger community is planting a larger crop of seeds that will come to fruition in the mid-2020s, and today’s seeds include startup biotechnology companies in the SENS space, new advocacy initiatives like LEAF hitting their stride, and so forth.

Thanks to the efforts of many advocates, yours included, public perception of rejuvenation is also shifting. How close do you think we are to widespread acceptance?

I don’t think acceptance matters – that might be the wrong term to focus on here. Acceptance will occur when the therapies are in the clinic. People will use them, and everyone will conveniently forget all the objections voiced. The most important thing is not acceptance but rather material support for development of therapies. The help of only a tiny fraction of the population is needed to fund the necessary research to a point of self-sustained development, and that is the important thing. Create beneficial change, and people will accept it. Yet, you cannot just go and ask a few people. Persuading many people is necessary because that is the path to obtaining the material support of the necessary few: people do not donate their time and funds to unpopular or unknown causes; rather, they tend to follow their social groups.

Last year, you talked about the importance of sustained advocacy being as important as supporting the research itself. You wrote about a number of approaches to advocacy, including ours. Have you noticed an improvement in the quality of advocacy since then, and do you still maintain that professional advocacy is as important to the cause as research is?

Fishing for compliments? I’m very pleased with the progression of LEAF and with advocacy in general in our space. People have come and gone over the years, but this latest group of advocates appears to have set up shop for the long term. That is important and a welcome change. I can’t keep writing Fight Aging! forever, if only because hands and schedules eventually give way under the accumulated burdens of the years. There must be far more voices doing this same sort of work, all in their own varied ways. Diversity and redundancy are both important aspects of advocacy – many people arguing in their own ways for a given point of view are needed in order to persuade the world at large.

Presently, rejuvenation is a relatively unknown topic; people who say they’re against this technology probably don’t think it’s a concrete possibility anyway. However, as more important milestones will be reached—for example, robust mouse rejuvenation—this might change. Do you think that these milestones will result in opponents changing their attitudes or becoming more entrenched?

Opposition to human rejuvenation therapies is almost entirely irrational; either (a) it’s a dismissal of an unfamiliar topic based on the heuristic that 95% of unfamiliar topics turn out to be not worth the effort when investigated further, or (b) it’s a rejection of anything that might result in sizable change in personal opinion, life, and plans, such as the acceptance of aging and death that people have struggled to attain. This sort of opposition isn’t based on an engagement with facts, so I think a sizable proportion of these folk will keep on being irrational in the face of just any scientific advance or other new factual presentation short of their physicians prescribing rejuvenation therapies to treat one or more of their current symptoms of aging.

On the other hand, there will be steady progress in winning people over in the sense of supporting rejuvenation in the same sense as supporting cancer research: they know nothing much about the details, but they know that near everyone supports cancer research, and cancer is generally agreed to be a bad thing, so they go along. Achieving this change is a bootstrapping progress of persuading opinion makers and broadcasters, people who are nodes in the network of society. Here, milestones and facts are much more helpful.

After years of financially supporting other rejuvenation startups, you’re now launching your own company focused on gene therapies relevant to rejuvenation. What drove your decision to do this?

In the course of funding companies, one learns a great deal about the bounds of what might be achieved and the sort of work that is needed: it isn’t uncommon for investors to become entrepreneurs and vice versa. There are large overlaps in the mental toolkits required, and it is a logical evolution seen from either side. Moreover, in the course of investing in startups, one meets people in the community, such as my cofounder Bill, who intend to both fund and run companies, and it turns out that we work together quite well. As in all such things, it has a lot more to do with happenstance leading to the right arrangements of people and much less to do with the technical landscape at the time.

Your company’s first objective is thymic regeneration. Why do you think the thymus is the ideal initial target for your work?

It is a very straightforward goal, with a lot of supporting evidence from the past few decades of research. It think it is important to set forth at the outset with something simple, direct, and focused, insofar as any biotechnology project can be said to have those attributes. This is a part of the SENS rejuvenation research agenda in the sense of cell atrophy: the core problem is loss of active thymic tissue, which leads to loss of T cell production and, consequently, immunodeficiency. However, the immune system is so core to the health of the individual that any form of restoration can beneficially affect a great many other systems. The many facets of the immune system don’t just kill off invading pathogens; they are also responsible for destroying problem cells (cancers, senescent cells), and they participate in tissue maintenance and function in many ways.

You are using gene therapy; why have you chosen this delivery method specifically and not, for example, a small-molecule approach?

If your aim is to raise or lower expression of a specific protein, and you don’t already have a small molecule that does pretty much what you want it to do without horrible side-effects, then you can pay $1-2M for a shot at finding a starting point in the standard drug discovery databases. That frequently doesn’t work, the odds of success are essentially unknown for any specific case, and the starting point then needs to be refined at further cost and odds of failure. This is, for example, the major sticking point for anyone wanting to build a small-molecule glucosepane breaker – the price of even starting to roll the dice is high, much larger than the funding any usual startup crew can obtain.

On the other hand, assuming you are working with a cell population that can be transduced by a gene therapy to a large enough degree to produce material effects, then $1-2M will fairly reliably get you all the way from the stage of two people in a room with an idea to the stage of having animal data sufficient enough to start the FDA approval process.

You are working with SRF spin-off company Ichor Therapeutics; what was the reason for choosing to work with Kelsey and the Ichor team?

Because they are great. Kelsey has achieved considerable success, bootstrapping from nothing but a plan, and has an excellent team. Their philosophy of development dovetails well with ours, both in terms of short-term development of a biotech startup and in the longer term of how we’d like to see this industry develop over the next 10-15 years.

Will your company focus on lab work, or do you plan to run human trials once a sufficiently advanced stage has been reached?

We’re absolutely signed up for the end-to-end path of getting a therapy into the clinic. That is the whole point of the exercise – to bring therapies into general availability. Of course, there will be a great deal of lab work to accomplish between here and there.

The FDA doesn’t recognize aging as a disease, so it won’t approve drugs to target it directly. Is this a problem for your company’s activities?

Remember that when talking to the FDA, one usually starts with just a small patient group with a single age-related condition, a fraction of everyone that might eventually be helped. This is done to control costs and ensure the best possible chance of a successful approval by narrowing the focus to a very clear, simple experiment. After this, one expands to larger patient groups and more expensive trials. As it happens, the effects of immunosenescence on health are so widespread and similar from individual to individual that it wouldn’t be hard to pick a clearly defined condition and patient population that covers near everyone in late life. Unfortunately, one would have to have very deep pockets indeed to pick that as the first option for entering the approval process – one has to work up to it.

What are Repair Biotechnologies’ possible future targets after thymic regeneration?

We’re looking into a couple of interesting options, guided by the SENS philosophy of damage repair, but it is very challenging to say at this stage which of them will prove the most advantageous to attempt. Obviously, at this stage, the primary focus has to be on success in our first venture.

What do you think are currently the most promising research avenues within each rejuvenation therapy subfield?

We have a challenge today in that we have the DNA of a patient advocacy community trying to get work to proceed at all. So, for fifteen years, our measure of success was “are people paying more attention to this?” Now, we have to start thinking like a development community, in which success revolves around “does this implementation actually work in humans, and how well does it work, and how much does it cost?”

In all too many cases, we don’t yet know the answers to these questions: the data isn’t there yet for senolytics, for example. So, you can look at senolytic efforts and know who has the most funding and attention but have no idea which of the therapeutic approaches actually represent the most significant progress at the end of the day. For all we know, dasatinib might turn out to be the most cost-effective of all of the current small-molecule approaches, with everything everyone has done since then coming in a poor second-best, and we won’t find this out for years, as no one has any incentive to run the necessary large-scale trials on an existing drug.

Dr. de Grey is hopeful, but not certain, that immunotherapy might make OncoSENS unnecessary. What do you think?

I have long thought that canonical OncoSENS – whole-body interdiction of lengthening of telomeres – might be rendered unnecessary by sufficiently advanced incremental progress in other areas of cancer research. That said, it should be so cost-effective that it is hard to imagine “sufficiently advanced incremental progress” not incorporating interference with telomeres in some way. People other than SENS-funded groups are working on it, after all.

If you think about it, restoring the immune system to youthful capacity should also help to achieve this goal; there is evidence to suggest that age-related immune dysfunction drives age-related cancer risk and that this correlates well with thymic decline. The world will still need highly effective, low-side-effect cancer therapies even if everyone has the cancer risk profile of a young adult, of course, but far less frequently.

What do you realistically expect might happen, over the next 25 years, in terms of rejuvenation research results, funding, clinical applications, and availability?

Well, that’s an essay in and of itself. I think my views on the technology itself are fairly widely known: I’ve written a few short essays on likely ordering of development. The funding will  continue to grow year-over-year to the degree that any success is achieved in the clinic. However, everything takes a very long time in medicine due to the way in which regulation works, no matter how fast the technology is running in the labs, and the pace of technological progress in biotechnology is accelerating. At some point, the system exemplified by the FDA will break because cheap and effective therapies coming out of the labs will be so far ahead of what is available in the clinic that they will leak out into some other form of commercial development. Who knows what that will look like? Perhaps it will be a network of overseas non-profits that run their own, lighter and faster, validations of trials and presentations of human data gathered from participating clinics. I think that next-generation gene therapies, evolutions of CRISPR, will likely precipitate this sort of reordering of the landscape.

Do you expect that aging might relatively soon be officially considered a disease, or a co-morbid syndrome, by WHO and the FDA?

No. Regulation typically lags behind reality by many years. What will probably take place is some sort of battle of wills and lawyers over widespread off-label use for rejuvenation therapies, most likely senolytics, that have only been narrowly approved for specific age-related conditions. That will go on for a while and, ultimately, generate sufficient critical press attention to induce regulators to back off from trying to suppress that off-label use and, instead, accept aging as an approved indication. This hypothetical scenario could run a decade or more from beginning to end.

The availability of rejuvenation therapies doesn’t depend only on their cost; it also depends on how they’re regulated in each specific country. Do you imagine “rejuvenation tourism” will exist for long, or at all, before these treatments are part of the standard medical toolkit everywhere?

The development of stem cell therapies is the example to look at here. These therapies were available via medical tourism for a decade prior to the first approved treatments in the US, and this continues to be the case even afterwards, as only a narrow slice of therapies have been approved. Medical regulation is slow-moving, and so medical tourism will be long-lasting. I think this will work exactly the same way for other broad classes of therapy, such as gene therapies.

What is, in your view, the biggest bottleneck to progress in aging research?

Either (a) the lack of funding for research and early-stage startup development or (b) the low number of entrepreneurs, one of the two. Probably funding, as money can be used to craft an 80/20 solution to the shortage of entrepreneurs, but entrepreneurs can only reliably solve the lack of funding problem if there are a lot of them. Almost every specific instance of things not moving forward that I’ve seen could be addressed by a well-thought-out application of funds to the situation.

The chasm between academic research and early-stage commercial development is also a sizable issue. The academic side does a terrible job of reaching out to find entrepreneurs and companies that can carry forward their research to benefit patients. The entire biotechnology industry (entrepreneurs, investors, bigger companies and funding entities) collectively does a terrible job of reaching back into the academic community to fund, encourage, and adopt the most promising research. So, projects that should move instead languish for years because no one is taking the obvious steps to improve on the situation.

Right now, there don’t seem to be any unexpected problems with the science that might jeopardize the development of rejuvenation. Do you think that any particular areas of research might run into difficulties down the road?

No. I think all the unexpected problems will be implementation details. It is perfectly possible to have the correct strategy and the wrong tactics, and this happens all the time in complex fields such as biotechnology – it doesn’t take much of an error in interpreting research results to derail the original plan and require a new direction. Most such challenges are short-term and can be worked around with some loss of time and money, but there are certainly past instances in which the company is lost because there is no viable way to salvage a better path.

This is what happened to one of the early AGE-breaker efforts, the development of ALT-711: removing AGEs still seems very much a correct approach to the age-related stiffening of tissues, but a drug that works in rodents will do nothing in people because the physiologically relevant AGEs are completely different. At that time, the researchers didn’t have that critical piece of information. We will no doubt see similar stories occur again in the future.

Caloric restriction and exercise may also potentially convey some small increase in life expectancy. Given that the goal is to reach longevity escape velocity, do you practice a particular diet or exercise program, and would you encourage people to consider such approaches?

I have always suggested that people look into the simple, reliable things they can do for better health. The way to look at this is through the lens of cost-effectiveness. Calorie restriction and exercise are cheap, easy, and highly reliable. They don’t adjust your life expectancy by decades, but since they are cheap, easy, and reliable, you should still look into it. There are many different ways to approach both, so just because an attempt fails or isn’t palatable, that’s no excuse to give up on the whole endeavor. At the end of the day, it is a personal choice, of course. We can always choose to be less healthy; that’s easy to do in the present environment.

You’ve written many articles on the topic of self-experimentation on FA. Can you summarize your views?

The current self-experimentation community – and here I include many disparate groups, only tenuously linked, with interests in nootropics, anti-aging, muscle building, and so forth – is woefully disorganized and ill-educated when it comes to the risks and scientific knowledge of the compounds they try. If one in twenty of the people who have tried dasatinib as a senolytic have (a) read the papers on pharmacokinetics in human volunteers, (b) recalculated likely human doses from the senolytic animal studies and compared them with human chemotherapy studies, or (c) actually tested the compound delivered by a supplier to ensure purity, I would be astoundingly surprised.

The bar for quality and safety in this community needs to be raised, and that is the primary purpose behind my writing articles on self-experimentation. Whatever I say, people are going to be out there trying senolytics – many of these compounds are cheap, easily available, and hyped. What they should be doing instead of rushing in is thinking for themselves and reading widely. If I can do a little to help make that happen, then all to the good.

What is your take-home message for our readers?

There is always a way to help accelerate the development of rejuvenation therapies – there is always something that one can do and feel good enough about doing to do it well. Don’t know what that something might be? Then talk with people in the community. Reach out, go to meetings, post online. Don’t force it. It will come to you in time.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. degree in mathematics; an amateur programmer; a hobbyist at novel writing, piano, and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.