Browsed by
Category: Guest Articles

Is Aging Natural, a Disease That We Can Treat, or Both? – Article by Steve Hill

Is Aging Natural, a Disease That We Can Treat, or Both? – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill explains that aging can be described as both natural and pathological without contradiction. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 16, 2018

Aging is something that we all share, rich or poor; it is something that happens to us all, and we are taught from a young age that it is inevitable. However, some scientists believe that aging is amenable to medical intervention and that such interventions could be the solution to preventing or reversing age-related diseases.

Academics are currently debating whether aging is natural or a pathological disease that we can treat.

In fact, there is now pressure from many academics to classify aging itself as a disease; indeed, doing so could potentially improve funding for aging research and help to speed up progress in finding solutions to age-related diseases. [1] The debate continues, but does it really matter if aging is classified as a disease, or is it largely a matter of semantics?

Fighting a losing battle

Current medical practice sees us trying to treat age-related diseases in the same way we do other diseases; this is the “infectious disease model”, and when it comes to treating age-related diseases, it is a losing battle.

The current approach works like this: as soon as a disease appears, the doctor attacks the disease using everything in the medical armory, and the patient can then continue with life until the next disease happens; this process is repeated until failure. This is an excellent way to deal with infectious diseases, and it has helped to increase life expectancy greatly in the last century; however, there are signs are that this approach is starting to run out of steam. [2-4]

Unfortunately, this “whack-a-mole” approach is a poor choice when it comes to treating the chronic diseases of old age. This is because the damage that the aging processes cause still continues to take its toll; therefore, treating the symptoms will ultimately achieve very little and certainly not cure the disease.

So, given that the aging processes lead to the diseases of aging, it is understandable that scientists are starting to consider aging itself to be a disease. While we do not yet fully understand all the intricacies of aging, we already know a great deal about the individual processes.[5] Certainly, we now know enough about aging to begin developing and testing interventions that directly target the underlying processes in order to prevent or treat pathology.

Treating the underlying processes and repairing their damage, which leads to the familiar diseases of old age, is the basis for the medical approach known as rejuvenation biotechnology, a multidisciplinary field that aims to prevent and treat age-related diseases by targeting the aging processes directly.

Aging is the foundation of age-related diseases

Even if aging is not a disease itself, the individual processes do lead to pathology and age-related diseases, such as cancer, heart disease, Parkinson’s, and Alzheimer’s. So, knowing that these processes create the conditions for diseases to develop, it makes sense to target the processes themselves in order to potentially prevent or treat a slew of age-related diseases at once.

The changes that aging brings vary from one person to another, but the common processes of aging are at work in all of us, albeit with some small variances between individuals. For example, we all suffer wear and tear in our joints due to the loss of cartilage, and we all experience the loss of skin elasticity due to the degradation of elastin and the failure of connective tissues. We all encounter other age-related changes, such as the accumulation of non-dividing senescent cells that cause chronic inflammation and disrupt tissue repair, and we also suffer from the accumulation of metabolic waste products that collect in our bodies over time.

As these changes progress, they eventually lead to the familiar diseases of aging. For example, lipids are critical for the function of our metabolism and are essential as part of our diet; however, over time, these processed lipids begin to accumulate in the blood vessel walls. Macrophages arrive to clear the toxic fatty waste away, but they become immobilized and die. This causes inflammation, attracting more macrophages and continuing the cycle. Ultimately, this debris forms plaques that harden the blood vessels and cause them to narrow; this causes blood pressure to rise and can eventually result in a heart attack or stroke.

This demonstrates that the normal metabolic processes that keep us alive ultimately lead to disease. Importantly, in this case, the early age-related changes that set the scene for disease progression, such as high cholesterol, have no symptoms. Nevertheless, such changes are the precursors of deadly diseases and are considered suitable targets for treatment. The same can be said for the other, more subtle, changes and damages that the aging processes cause.

Age-related conditions, such as arthritis, diabetes, osteoporosis, Alzheimer’s, Parkinson’s and many cancers, all follow this dynamic. Simply put, given the sufficient passage of time, the aging processes will cause us to suffer from multiple diseases. Therefore, we should consider these diseases to be the clinical manifestation of these age-related changes. In fact, medicine has been fighting against age-related changes for a long time, even if it was not obvious. For example, a doctor recommending that his patient should reduce his fat and carbohydrate intake to delay heart disease is already fighting those age-related changes. The diabetic who modifies her diet to better manage blood sugar levels is also doing the same thing.

Some people might contest this point of view, stating that the aging process is “natural” and therefore cannot be a disease. The argument that natural things are always good, the appeal to nature, is a logical fallacy. Such people may see natural and pathological as being mutually exclusive. Thus, what is natural must always be good, and what is pathological is bad, and so it cannot also be natural. This is, of course, false when you consider the meaning of each word. Natural simply means something that follows the normal, established course of events, and pathological means something that is harmful.

Conclusion

So, is aging natural or pathological? Well, by the dictionary definitions, aging can be described as both natural and pathological without contradiction.

Additionally, as it is currently classified, aging could be considered a syndrome, specifically a co-morbid syndrome. This really does describe aging perfectly; it is a group of symptoms that consistently occur together and a condition characterized by a set of associated symptoms. Ultimately, aging is an umbrella term describing a range of pathological changes; it may struggle to be accepted as a disease, but it already qualifies as a syndrome.

However, the question of aging being a disease or not is essentially semantic in nature. What rejuvenation biotechnology seeks to achieve is nothing more than preventing age-related diseases by treating the early stages of pathology, which are considered a natural process. While these early age-related changes have not been given a disease name, they are instrumental in the development of diseases, and surely, when it comes to medical treatment, that is all that matters.

References

[1] Bulterijs, S., Hull, R. S., Björk, V. C., & Roy, A. G. (2015). It is time to classify biological aging as a disease. Frontiers in genetics, 6.

[2] Crimmins, E. M. (2015). Lifespan and healthspan: Past, present, and promise. The Gerontologist, 55(6), 901-911.

[3] Olshansky, S. J., Passaro, D. J., Hershow, R. C., Layden, J., Carnes, B. A., Brody, J., … & Ludwig, D. S. (2005). A potential decline in life expectancy in the United States in the 21st century. New England Journal of Medicine, 352(11), 1138-1145.

[4] Reither, E. N., Olshansky, S. J., & Yang, Y. (2011). New forecasting methodology indicates more disease and earlier mortality ahead for today’s younger Americans. Health Affairs, 10-1377.

[5] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

About  Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Hallmarks of Aging: Deregulated Nutrient Sensing – Article by Ariah Mackie

The Hallmarks of Aging: Deregulated Nutrient Sensing – Article by Ariah Mackie

Ariah Mackie


Editor’s Note: In this article, Ariah Mackie explains that there are four key proteins involved in nutrient sensing that might be key contributors to aging.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 15, 2018

As part of our ongoing series covering the hallmarks of aging, we are taking a look at deregulated nutrient sensing today and how these four pathways regulate metabolism and influence aging.

To understand studies on nutrient sensing in the context of aging, let’s introduce four key protein groups. In this post, we’ll explore the pathways they help control and how they affect aging. These key proteins are IGF-1, mTOR, sirtuins, and AMPK [2]. We call these proteins “nutrient sensing” because nutrient levels influence their activity [2].

IGF-1 and the IIS pathway: The Basics

Insulin-like growth factor (IGF-1) inhibits the secretion of growth hormone (GH) by binding to a special receptor on the surface of a cell [1]. Like insulin, IGF-1 takes part in glucose sensing. Both it and insulin are part of the aptly named “insulin and insulin-like growth factor” (IIS) pathway [2].

Attenuation of the IGF-1/GH pathway (IIS) appears to improve lifespan in several model organisms [1]. For example, PI3K mice, which have a weakened IIS pathway, live longer [2]. Additionally, FOXO, a transcription factor (a protein that affects the production of RNA), lengthens lifespans in worms and fruit flies by attenuating IIS signaling [2]. In other studies, IGF-1 improves healthspan even when it does not lengthen lifespan [2].

There’s also evidence of a harmful impact when IGF-1 activity is high. Higher levels of IGF-1 are associated with increased risk of some types of cancer [1]. This increased cancer risk might be due to IGF’s ability to promote pathways that result in increased cell production [1].

IIS and the Not-So-Basics

IGF-1 expression and the IIS pathway are a bit of a paradox. Since it looks like turning down the IIS pathway promotes longevity, you might expect the IIS pathway to be very active in old organisms. It looks like high IIS ages us, after all. However, that’s not the case. In both accelerated and normal aging models, we see that the IIS pathway decreases [2].

One explanation for this weirdness is that it’s a last-ditch measure of the organism to increase its own lifespan. Yet, this short-term decrease in IIS activity can be harmful. In fact, it is so harmful that IGF-1 supplementation is beneficial [2]. What this seems to point to is a dichotomy concerning the expression of IIS. Overall, it looks like turning down the IIS pathway is good over the long term for longevity. This might be because it causes the reduction of metabolism and cell growth, which lessens wear and tear [2]. However, the body’s attempt to do the same in later life goes too far and too late to be truly beneficial.

How IGF-1 affects human lifespan is still fuzzy as well [1]. On one hand, there is an indication of a longevity effect with reduced IGF-1 activity in those with Laron syndrome (who don’t have functional growth hormone receptors), female nonagenarians, and extremely long-lived people [1]. Yet, the epidemiological data is not clear enough to be conclusive on IGF-1’s effects on humans [1]. This is partially due to the difficulty of structuring epidemiological studies on IGF-1, as many external factors, such as nutrition, can confound results [1].

mTOR

Mechanistic target of rapamycin (mTOR) is composed of the mTORC1 and mTORC2 protein complexes. It senses amino acids and is associated with a nutrient abundance [2]. It is a kinase, which means it adds phosphates to molecules [2]. mTOR is a champion regulator of anabolic metabolism [2], the process of building new proteins and tissues. In this way, how it functions is similar to the IIS pathway [2]. At any given moment, the metabolism is either breaking down old parts (catabolism) or building new ones (anabolism). Both mTOR and the IIS are part of the anabolic side of metabolism.

Lower activity of mTOR lengthens lifespan in model organisms, such as mice, yeast, worms, and flies [2]. Along those lines, mTOR activity increases in the hypothalami of aged mice, which promotes late-life obesity. With rapamycin, an inhibitor of mTOR, these effects are ameliorated [2]. As is the case with, IIS, lowered expression of mTOR is not always beneficial. Low expression of mTOR can harm healing and insulin sensitivity and can cause cataracts and testicular generation in mouse models [2].

Sirtuins

Sirtuins are a family of proteins that act as NAD(+) dependent histone deacetylases [2]. To explain what that means, let’s start with histones. Histones are the proteins that DNA wraps around. They serve as a way to compact the DNA (which is very long) in the nucleus, especially during cell division. Histones also help control the expression of genes by spatially making some genes more or less available for proteins like RNA polymerase to attach. On histones, there are lysines, a type of amino acid. It is on these lysines that histone deacetylases remove acetyl groups, which are small molecules. If that sounds too confusing, remember this: adding or removing acetyl groups helps control the expression of genes. In such a manner, sirtuins help control gene expression.

Sirtuins detect when energy levels are low by sensing the coinciding increase of NAD+ [2]. They also help control catabolic metabolism [2]. Upregulating some sirtuins produces anti-aging or health-promoting effects [2]. However, some sirtuins have only weak effects in some species, which makes summarizing their effects difficult. For example, in worms, higher expression of SIR2 yields only slight gains in longevity [2]. Overexpression of SIR2’s most similar counterpart in mice, SIRT1, appears to improve health during aging but not lifespan [2].

Another mouse sirtuin, SIRT6, seems to promote longevity more robustly [2]. Mice deficient in it experience accelerated aging. Conversely, turning it up results in increased longevity [2]. There is also SIRT3, which has been shown to help the regeneration ability of old hematopoietic (blood and immune cell producing) cells when overexpressed [2].

AMPK

AMP-activated kinase (AMPK) senses AMP (adenosine monophosphate) and ADP (adenosine diphosphate). These long-named molecules are present in higher quantities when nutrients are scarce [2].Therefore, it is easiest to remember AMPK as a sensor of fasted or calorie-restricted states and catabolism [2]. Molecularly, AMPK acts by adding phosphates to serine and threonine [3]. By doing so, AMPK helps regulate metabolism [2].

Like sirtuins, higher activity of AMPK has longevity-promoting effects [2]. To illustrate, metformin, a diabetes drug that appears to have a life-extension effect, activates AMPK in mice and worms [2]. Calorie restriction, which is known to increase lifespan in at least short-lived animals, can also increase the activity of AMPK [3]. Conversely, less AMPK sensitivity due to cellular stress results in oxidative stress, reduced autophagy, metabolic syndrome, more fat disposition, and inflammation [3].

Conclusion

In summary, there are four key proteins involved in nutrient sensing that might be key contributors to aging. Turning down the pathways of the first two, IGF-1 and mTOR, promote longevity. Both of these are involved in anabolic metabolism (building tissues) and increase in states of nutrient abundance[2]. Conversely, turning up the activity of the last two, sirtuins and AMPK, helps longevity. They work to promote catabolic metabolism (breaking down tissues) and increase with nutrient scarcity [2].

References

[1] Milman, S., Huffman, D. M., & Barzilai, N. (2016). The Somatotropic Axis in Human Aging: Framework for the Current State of Knowledge and Future Research. Cell Metabolism, 23(6), 980-989. doi:10.1016/j.cmet.2016.05.014

[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[3] Salminen, A., & Kaarniranta, K. (2012). AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Research Reviews, 11(2), 230-241. doi:10.1016/j.arr.2011.12.005

About Ariah Mackie

Ariah received a Bachelor’s Degree in Biomolecular Engineering from the University of California in Santa Cruz in 2016. Her career interests are in regenerative medicine for aging, teaching, computational biology, genomics, and bioinformatics.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Could Filtering Our Aged Blood Keep us Young? – Article by Steve Hill and Nicola Bagalà

Could Filtering Our Aged Blood Keep us Young? – Article by Steve Hill and Nicola Bagalà

Steve Hill

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill present the interview they conducted with Dr. Irina Conboy of Berkeley University and Dr. Michael Conboy of Havard University on the topic of youthful blood.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 17, 2018

Due to a recently published study on the effects of young plasma on aged mice, we got in touch with Dr. Irina Conboy of Berkeley University. Dr. Conboy is an Associate Professor at the Department of Bioengineering and an expert in stem cell niche engineering, tissue repair, stem cell aging and rejuvenation. Before we dive into the main topic, let’s familiarize ourselves a little with Dr. Conboy and her work.

Dr. Conboy got her Ph.D. at Stanford University, focusing on autoimmunity. She met her partner in science—and in life—Dr. Michael Conboy at Harvard and they got married before embarking on graduate studies; they celebrated their Silver Anniversary a few years ago. During her postdoctoral studies, she began focusing on muscle stem cells, trying to figure out what directs them to make new healthy tissue and what causes them to lose their ability to regenerate the tissues they reside in as we age [1].

Together with her husband Michael, she eventually discovered that old stem cells could be reactivated and made to behave like young ones if appropriately stimulated. The Conboys’ parabiosis experiments—which consisted in hooking up the circulatory systems of aged and young mice—showed that old age is not set in stone and can be reversed in a matter of weeks [2].

The follow-up work by the Conboys uncovered that age-accumulated proteins, such as TGF-β1, inhibited stem cells’ ability to repair tissues even in young mice, and when TGF-β1 signaling is normalized to its young levels, old mice (equivalent to 80-year old people) have youthful muscle regeneration and better neurogenesis in the hippocampus (the area of the brain that is responsible for memory and learning) [3].

While young blood did appear to be beneficial to old stem cells, their evidence suggested that the real culprit of the broad loss of tissue repair with age was the negative influence of age-accumulated inhibitory proteins in aged tissues and circulation, also called the stem cell niche [4].

This conclusion is certainly compatible with the view of aging as a damage accumulation process [5]. As Irina herself pointed out in this interview, in the parabiosis experiments, the old mice had access to the more efficient young organs: lungs, liver, kidneys and immune system of the younger mice, which likely accounted for many of the benefits observed in the elderly parabiosed mice. With respect to the rejuvenation of the brain, the old mice experienced environmental enrichment by being sutured to young, more active parabionts, and this is known to improve the formation of new brain cells, learning, and memory.

An aged niche blocks the action of old and young stem cells alike very quickly; therefore, as Dr. Conboy observed in an article in the Journal of Cell Biology, we can’t treat the diseases of aging by simply transplanting more stem cells, because they will just stop working. Their niche needs to be appropriately engineered as well. Fortunately, there are potential solutions to this problem; such as the use of artificial gel niches and defined pharmacology that are designed to protect transplanted or endogenous stem cells from the deleterious environment of the old body.

This research holds the potential to significantly postpone the onset of age-related diseases and possibly reverse them one day, including frailty, muscle wasting, cognitive decline, liver adiposity and metabolic failure, but Dr. Conboy remains cautious about the possibilities until more data is in. However, she does think that longer and healthier productive lives could improve people’s attitudes towards the environment and treating each other with compassion and respect—a view that we definitely share.

We managed to catch up with Irina and Michael Conboy and talk to them about their work.

For the sake of those new to the topic, what is it in young blood and aged blood that affects aging?

Irina: Numerous changes in the levels of proteins that together regulate cell and tissue metabolism throughout the body.

Mike: We wondered why almost every tissue and organ in the body age together and at a similar rate, and from the parabiosis and blood exchange work now think that young blood has several positive factors, and old blood accumulates several negative, “pro-aging” factors.

A lot of media attention and funding is currently being directed to youthful blood transfusions; how can we move beyond this to potentially more promising approaches, such as filtering and calibration of aged blood?

Irina: People need to understand not just the titles, abstracts and popular highlights of research papers, but the results and whether they support (or not) the promise of rejuvenation by young blood. In contrast to vampire stories, we have no strong experimental evidence that this is true, and there is a lot of evidence that infusing your body with someone else’s blood has severe side effects (even if it is cell-free).

Mike: Translational research!

Some evidence suggests dilution is the most likely reason that young blood has some beneficial effects; what are your thoughts on this recent study [6] in rats that shows improved hepatic function partially via the restoration of autophagy?

Irina: There are certainly “young” blood factors that are beneficial, not just a dilution of the old blood, and this benefit differs from organ to organ. We have published on improved liver regeneration, reduced fibrosis and adiposity by transfusion of old mice with young blood, but these are genetically matched animals, and in people, we do not have our own identical but much younger twins [7].

If dilution is also playing a role here, then can we expect similar or better results from calibrating aged blood?

Irina: Yes, and our work in progress supports the idea.

In your 2015 paper, you identified that TGF-β1 can be either pro-youthful or pro-aging in nature, depending on its level [8]. In the study, you periodically used an Alk-5 inhibitor to reduce TGF-β1 levels and promote regeneration in various tissues. In the study, you showed that TGF-β1 was important in myogenesis and neurogenesis; is there reason to believe that this mechanism might be ubiquitous in all tissues?

Irina: Yes, because TGF-β1 receptors are present in most cells and tissues.

Also, TGF-β1 is only one of a number of factors that need to be carefully balanced in order to create a pro-youthful signalling environment. How many factors do you believe we will need to calibrate?

Irina: There will be a certain benefit from calibrating just TGF-beta 1, but also additional benefits from more than one or just TGF-beta.

How do you propose to balance this cocktail of factors in aged blood to promote a youthful tissue environment?

Irina: We are working on the NextGen blood apheresis devices to accomplish this.

So, you are adapting the plasmapheresis process to effectively “scrub” aged blood clean and then return it to the patient. This would remove the need to transfuse blood from young people, as your own blood could be filtered and returned to you, and no immune reaction either, right?

Irina: Accurate.

This plasmapheresis technique is already approved by the FDA, we believe, so this should help you to develop your project faster, right?

Irina: Exactly.

Do you think a small molecule approach is a viable and, more importantly, a logistically practical approach to calibrate all these factors compared to filtering aged blood?

Irina: Yes, it is a very feasible alternative to the NextGen apheresis that we are working and publishing on.

It is thought that altered signaling is caused by other aging hallmarks higher up in the chain of events; even if we can “scrub” aged blood clean, is it likely to have a long-lasting effect, or would the factors reach pro-aging levels fairly quickly again if nothing is done about the other hallmarks antagonizing them?

Irina: That needs to be established experimentally, but due to the many feedback loops at the levels of proteins, genes and epigenetics, the acquired youthful state might persist.

Ultimately, could a wearable or an implanted device that constantly filters the blood be the solution to these quickly accumulating factors?

Irina: Maybe, but the first step of a day at a NextGen apheresis clinic once every few months might be more realistic.

Filtering seems to be a far more practical solution, so how are you progressing on the road to clinical trials?

Irina: We are collaborating with Dr. Dobri Kiprov, who is a practicing blood apheresis physician with 35 years of experience, and he is interested in repositioning this treatment for alleviating age-related illnesses.

Senolytics and removing senescent cells and the resulting inflammation they cause during the aging process has become a hot topic in the last year or so. What are your thoughts on senolytics as a potential co-therapy with a blood filtering approach?

Irina: Might be good, but we should be careful, as p16 is a normal, good gene that is needed for many productive activities by many cells.

What do you think it will take for the government to fully support the push to develop rejuvenation biotechnology?

Irina: Clear understanding of the current progress and separating the real science from snake oil is very important for guiding funding toward realistic clinical translation and away from the myth and hype.

The field is making amazing progress, but, sadly, it is plagued by snake oil. As much as an “anti-aging free market” encourages innovation, it also encourages hucksters. How can a member of the public tell the difference between credible science and snake oil?

Irina: I was thinking for some time about starting a popularized journal club webpage where ordinary people can see what we typically critically point out in the lab setting about published papers and clinical trials.

How can our readers learn more about your work and support your research?

Irina: The new Conboy lab website is coming up; meanwhile, contact me and Dr. Mike at iconboy@berkeley.edu and conboymj@berkeley.edu

Conclusion

We would like to thank Irina and Michael for taking the time to answer our questions and for providing the readers with a fascinating insight into their work.

Literature

[1] Conboy, I. M., Conboy, M. J., Smythe, G. M., & Rando, T. A. (2003). Notch-mediated restoration of regenerative potential to aged muscle. Science, 302(5650), 1575-1577.

[2] Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433(7027), 760-764.

[3] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.

[4] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature communications, 7.

[5] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[6] Liu, A., Guo, E., Yang, J., Yang, Y., Liu, S., Jiang, X., … & Gewirtz, D. A. (2017). Young plasma reverses age‐dependent alterations in hepatic function through the restoration of autophagy. Aging cell.

[7] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature communications, 7.

[8] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Abolition of Aging – A Book Review – Article by Nicola Bagalà

The Abolition of Aging – A Book Review – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà provides a book review of the book The Abolition of Aging by David Wood, a book which explains in great detail the benefits that would derive from a successful implementation of the “rejuveneering project”.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 13, 2018

As you might recall, in my review of Ending Aging, I said that the book could have benefited from a more in-depth discussion of the benefits of rejuvenation as well as the concerns and objections often raised against it. Anyone else sharing the same feeling will find what they’re looking for in The Abolition of Aging, by Chair of London Futurists David Wood.

Written in an elegant, clear style, The Abolition of Aging brilliantly accomplishes the difficult task of guiding the reader through all the turns and twists of the topic, explaining in great detail the benefits that would derive from a successful implementation of the “rejuveneering project”—as Wood calls it—presenting all the typical objections and related counterarguments, and—in the words of 3G Doctor Director David Doherty—providing innumerable “stunning references and observations”.

Just like there’s no time to waste if we want to defeat aging in time for currently living people to benefit, Wood wastes no time with lengthy preambles; the very first line of the foreword comes directly to the point, bluntly stating what readers unfamiliar with the topic may find shocking: the possibility of eliminating biological aging is now within striking distance.

Possibly preventing the reader’s reaction, the author immediately gives a preliminary discussion of the traditional responses to his claim: “it’s not possible” and “it’s not desirable”, which Wood ascribes—correctly, in my opinion—in no small part to a great desire to avoid an unpleasant discussion that would force us to reconsider many assumptions on the inevitable finitude of human existence, with which most of us have already made our peace.

To succeed in his task of getting us to snap out of a multi-millenary Stockholm syndrome that pushes humanity to praise the tyranny of old age, Wood resorts to every weapon in his arsenal, making a very convincing case that rejuvenation is very much desirable as well as possible.

Skeptics who assume that the technology necessary to rejuvenate people is centuries away will be surprised to learn about how advanced the field actually is and how much faster it is likely to grow than conventional wisdom would have it. The word of senior scientists who claim that the reversal of aging is nothing but a pipe dream, as Wood warns us, should be taken with a grain of salt: The Abolition of Aging provides plenty of examples of luminaries and eminent experts of the past summarily dismissing scientific theories and technologies that today are well-established and taken for granted by everyone. (Among many such examples, one I really cannot abstain from mentioning is the hilariously wrong 1903 prediction by the New York Times that human flight, if at all possible, would take one to ten million years to come true. Less than 70 years later, not only was human flight commonplace, but human beings had landed on the Moon.)

Nonetheless, Wood’s optimism should not be mistaken for complacency. He makes no mystery that the success of the rejuveneering project is a mere possibility, however likely, and not at all a certainty. Many are the unknowns—scientific, political, societal, financial, and more—that could well thwart our efforts in this direction if we’re not careful. Wood offers advice on how to deal with these issues standing in the way of an aging-free world as well as those that might lurk beyond. After all, the functioning of society as we know it hinges on the existence of aging; our lives, our policies, and our customs are built around it. Eliminating aging would require a serious rethinking of much of society’s inner workings, and this operation is not free of risks, as Wood rightfully concedes. Great changes for the better often come with potential downsides, but we should not let this deter us; rather, we should appreciate how the fruits to be reaped are well worth the potential risks involved and act now to prevent or mitigate any unwanted consequences. A world without aging would need to be managed in a different way, but that is not a problem.

A particular obstacle on the way to a world without aging is represented by adverse psychology, to which Wood dedicates an entire chapter. Ever since we had the ability to reflect upon ourselves and the human condition, as the author explains, we’ve had to face our own mortality and fear of death. Fear of death is a very useful adaptation to increase the chance that an individual will live long enough to reproduce, but in the case of a highly self-aware species like us, it’s a double-edged sword. Our deep desire to express ourselves, to learn, create, grow, to live, inevitably clashes against the knowledge of our apparently inescapable demise.

If left unresolved, this inner conflict could strike terror so paralyzing that living our lives would be impossible. With no hope of defeating an apparently all-powerful enemy such as death, the young human race had to devise other ways out of this conundrum—psychological expedients to sugar the pill or even make it appear better than the alternative; for some, having children, creating art, changing the world through their work and so on may all offer the comforting thought of their legacy, and thus part of themselves, carrying on at least to some extent; believers have faith that their immortal souls will continue existing even after their bodies will have perished; others assume a world without death would, for one reason or another, be so unbearable that oblivion would be preferable.

These mental devices have existed for so long that they’ve shaped our society and our morals; accepting death has become a sign of wisdom while trying to avoid or delay it when “the right time” has come is seen as a sign of immaturity and selfishness. These views are so entrenched in most people that any attempt to question their validity is likely to trigger aggressive defensive reactions or, sometimes, contempt and ridicule. For these reasons, life extension is not an easy idea to sell. In his detailed discussion, though, Wood provides valuable advice to ease the advocates’ task, listing the dos and don’ts of how to present the subject.

Rejuvenation is not all the book deals with. Wood’s futurist soul fully reveals itself in his vision of the futures of humanity, faith, and death, which are discussed in the chapter “Towards Humanity+” as well as in the possibilities outlined in chapter 12, “Radical alternatives”, such as cryonics, head transplants, and mind uploading. While these ideas are often plagued by abundant hype and unjustified premature enthusiasm, I find that Wood simply presented relevant facts as they are, with an appropriate dose of healthy skepticism where needed but without any undue disbelief. Cryonics in particular, which is usually unjustly regarded as a scam to part rich fools from their money, is presented as a valid backup plan for those who don’t expect to live long enough to see the dawn of rejuvenation; just like cryonics companies themselves, Wood makes no mystery that it is uncertain if bringing back to life cryopreserved patients will ever be possible, despite encouraging successes with transplantation of cryopreserved animal organs. Then again, I would add that if the chances of coming back to life from cryopreservation are uncertain, there’s no chance whatsoever of coming back after being buried or cremated.

Summing up, I believe that The Abolition of Aging is a must-read for experienced advocates and newcomers alike. People who haven’t made up their minds about supporting rejuvenation will be fully equipped to make an informed decision after reading this book, or, at the very least, will be able to research the topic further; advocates will have plenty of references and useful information for their advocacy efforts. Together with Ending Aging, this book answers pretty much all the whats, whens, hows, and whys to the best of our current understanding.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Financing the Future – Article by R. Nicholas Starr

Financing the Future – Article by R. Nicholas Starr

logo_bg

R. Nicholas Starr


Editor’s Note: As noted by the author, Mr. Starr, the U.S. Transhumanist Party publishes this article to motivate discussion on a topic where individual transhumanists have varying perspectives. In May 2017 the U.S. Transhumanist Party adopted the following position on taxation in its Platform in Article III, Section XXXVI, of its Constitution:

Section XXXVI [Adopted by a vote of the members during May 7-13, 2017]: The United States Transhumanist Party supports the elimination of graduated taxation and income taxation more generally. Instead, the United States Transhumanist Party advocates a flat percentage-of-sales tax applicable only to purchases from businesses whose combined nationwide revenues from all affiliates exceed a specified threshold. This tax should be built into the price of goods from such large businesses and should not impede transaction efficiency in any manner. Transactions pertaining to wages, salaries, gifts, donations, barter, employee benefits, and inheritances should remain completely untaxed, as should transactions involving solely individuals and/or small businesses, for whom the establishment of a tax-reporting infrastructure would be onerous. Furthermore, all taxes on land and property should be abolished.

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, February 6, 2018


Since 2016, the U.S. Transhumanist Party has expanded, both in membership and in policy initiatives. And while we have created an ideal foundation for how we want to change our country and our world, voting on ideas isn’t enough. We must take the next step making these ambitions a reality, and it is one step that many of us would rather avoid talking about: how do we pay for all of this?

Individual transhumanists come from all shades of the fiscal spectrum. Many believe that a techno-libertarian approach would be the best way to fund the transhumanist movement, while others look towards traditional taxation methods to provide the necessary capital. While there are many ways to skin this lab-grown bio-engineered pig, the Party as a singular entity needs to determine the best method for funding our lofty goals.

Allow me to make the first controversial suggestion.

The United States is, at this point, completely reliant on capitalism. So reliant, in fact, that we lean on it for political-decision making like the exoskeletons we hope to mass produce in the near future. It’s what holds this country up. And yet it is this political-economic system that is creating staggering wealth inequality. Corporations continue to grow massive wealth while the general public struggles to afford their products.

I propose reorganizing the tax structure so that corporations actually pay taxes and eliminate personal income taxes. By relieving this financial burden on the American citizen, it is possible to enable people to actually afford to improve their lives while increasing the amount of money running through the economy. Sadly, removing personal income tax is not enough, especially when you begin to consider that many employees will likely be replaced by automation. Simply put, corporate entities need pay up. They need to support the political system that supports them. But will that cause business to simply abandon the country all together? While technically possible, it seems unlikely. For as long as there are consumers in the country, business will always want to be located as close as possible to their target market.

There is also an option to modify the above recommendation. Automating the workforce comes with some financial burdens, this has been widely discussed. But there is another, less thought of, burden – that of computing power. How can large-scale automation be achieved without large-scale processing? So instead of shifting the tax burden entirely from individuals to businesses, we could establish a blockchain distribution of computing that businesses would pay individuals to use during times when your computer is otherwise idle. A modest portion would then be taxed to support the infrastructure that both the business and the individual are using. In essence, this is a Universal Basic Income that is supported by capitalism.

Is this an oversimplification of a complex issue? Yes. And I hope that the neglected details spark a healthy and productive discussion on the matter. This is just the opinion of one member, and not the position of the U.S. Transhumanist Party. I encourage every reader to give their thoughts on this difficult and divisive topic in the comments.

Ryan Starr (R. Nicholas Starr) is the is the leader of the Transhumanist Party of Colorado and founder of the Transhumanists of the Sierras

We Must Unite for an International Ban on AI Weaponry; A Real Solution to Survive the Singularity Along with What Lies Beyond – Article by Bobby Ridge

We Must Unite for an International Ban on AI Weaponry; A Real Solution to Survive the Singularity Along with What Lies Beyond – Article by Bobby Ridge

Bobby Ridge


I urge the United States Transhumanist Party to support an international ban on the use of autonomous weapons and support subsidies from governments and alternative funding into research for AI safety – funding that is very similar to Elon Musk’s efforts. Max Tegmark recently stated that “Elon Musk’s $10M donation to the Future of Life Institute that helped put out 37 grants to run a global research program aimed at keeping AI beneficial to humanity.”

Biologists fought hard to pass the international ban on biological weapons, so that the name of biology would be known as it is today, i.e., a science that cures diseases, ends suffering, and makes sense of the complexity of living organisms. Similarly, the community of chemists also united and achieved an international ban on the use of chemical weapons. Scientists conducting AI research should follow their predecessors’ wisdom and unite to achieve an international ban on autonomous weapons! It is sad to say that we are already losing this fight for an international ban on autonomous weapons. The Kalashnikov Bureau weapons manufacturing company announced that they have recently invented an unmanned ground vehicle (UGV), which field tests have already shown better than human level intelligence. China recently began field-testing cruise missiles with AI and autonomous capabilities, and a few companies are getting very close to having AI autopilot operating to control the flight envelope at hypersonic speeds. (Amir Husain: “The Sentient Machine: The Coming Age of Artificial Intelligence“)

Even though, in 2015 and 1016, the US government spent only $1.1 billion and $1.2 billion in AI research, respectively, according to Reuters, “The Pentagon’s fiscal 2017 budget request will include $12 billion to $15 billion to fund war gaming, experimentation and the demonstration of new technologies aimed at ensuring a continued military edge over China and Russia.” While these autonomous weapons are already being developed, the UN Convention on Certain Conventional Weapons (CCW) couldn’t even come up with a definition for autonomous weapons after 4 years of meeting up, despite their explicit expression for a dire concern for the spread of autonomous weapons. They decided to put off the conversation another year, but we all know that at the pace technology is advancing, we may not have another year to postpone a definition and solutions. Our species must advocate and emulate the 23 Asilomar AI principles, which over 1000 expert AI researchers from all around the globe have signed.

In only the last decade or so, there has been a combined investment of trillions of dollars towards an AI race from the private sector, such as, Google, Microsoft, Facebook, Amazon, Alibaba, Baidu, and other tech titans, along with whole governments, such as, China, South Korea, Russia, Canada, and only recently the USA. The investments are mainly towards making AI more powerful, but not safer! Yes, the intelligence and sentience of artificial superintelligence (ASI) will be inherently uncontrollable. As a metaphor, humans controlling the development of ASI, will be like an ant trying to control the human development of a NASA space station on top of their ant colony. Before we get to that point, at which hopefully this issue will be solved by a brain-computer-interface, we can get close to making the development of artificial general intelligence (AGI) and weak ASI safe, by steering AI research efforts towards solving the alignment problem, the control problem, and other problems in the field. This can be done with proper funding from the tech titans and governments.

“AI will be the new electricity. Electricity has changed every industry and AI will do the same but even more of an impact.” – Andrew Ng

“Machine learning and AI will empower and improve every business, every government organization, philanthropy, basically there is no institution in the world that cannot be improved by machine learning.” – Jeff Bezos

ANI (artificial narrow intelligence) and AGI (artificial general intelligence) by themselves have the potential to alleviate an incomprehensible amount of suffering and diseases around the world, and in the next few decades, the hammer of biotechnology and nanotechnology will likely come down to cure all diseases. If the trends of information technologies continue to accelerate, which they certainly will, then in the next decade or so an ASI will be developed. This God-like intelligence will immigrate for resources in space and will scale to an intragalactic size. To iterate old news, to keep up with this new being, we are likely to connect our brains to it via brain-computer-interface.

“The last time something so important like this has happened was maybe 4.2 billion-years-ago, when life was invented.” – Juergen Schmidhuber

Due to independent assortment of chromosomes during meiosis, you roughly have a 1 in 70 trillionth of a chance at living. Now multiply this 70-trillionth by the probability of crossing over, and the process of crossing over has orders of magnitude more possible outcomes than 70 trillion. Then multiply this by probability of random fertilization (the chances of your parents meeting and copulating). Then multiply whatever that number is by similar probabilities for all our ancestors for hundreds of millions of years – ancestors that have also survived asteroid impacts, plagues, famine, predators, and other perils. You may be feeling pretty lucky, but on top of all of that science and technology is about to prevent and cure any disease we may come across, and we will see this new intelligence emerge in our laboratories all around the world. Any attempt to provide a linguistic description for how spectacularly LUCKY we are to be alive right now and to experience this scientific revolution, will be an abysmally disingenuous description, as compared to how truly lucky we all are. AI experts, Transhumanists, Singularitarians, and all others who understand this revolution have an obligation to provide every person with an educated option that they could pursue if they desire to take part in indefinite longevity, augmentation into superintelligence, and whatever lies beyond the Singularity 10-30 years from now.

There are many other potential sources existential threats, such as synthetic biology, nuclear war, the climate crisis, molecular nanotechnology, totalitarianism-enabling technologies, super volcanoes, asteroids, biowarfare, human modification, geoengineering, etc. Mistakes in only one of these areas could cause our species to go extinct, which is the definition of an existential risk. Science created some of these existential risks, and only Science will prevent them. Philosophy, religion, complementary alternative medicines, and any other proposed scientific demarcation will not solve these existential risks, along with the myriad of other individual suffering and death that occurs daily. With this recent advancement, Carl Sagan’s priceless wisdom has become even more palpable than before; “we have arranged a society based on Science and technology, in which no one understands anything about Science and technology and this combustible mixture of ignorance and power sooner or later is going to blow up in our faces.” The best chance we have of surviving this next 30 years and whatever is beyond the Singularity is by transitioning to a Science-Based Species. A Science-Based Species is like Dr. Steven Novella’s recent advocacy, which calls for transition off Evidence-Based medicine to a Science-Based medicine. Dr. Novella and his team understand that “the best method for determining which interventions and health products are safe and effective is, without question, good science.” Why arbitrarily claim this only for medicine? I propose a K-12 educational system that teaches the PROCESS of Science. Only when the majority of ~8 billion people are scientifically literate and when public reason is guided by non-controversial scientific results and non-controversial methods, then we will be cable of managing these scientific tools – tools that could take our jobs, can cause incomprehensible levels of suffering, and kill us all; tools that are currently in our possession; and tools that continue to become more powerful, to democratize, dematerialize, and demonetize at an exponential rate. I cannot stress enough that ‘scientifically literate’ means that the people are adept at utilizing the PROCESS of Science.

Bobby Ridge is the Secretary-Treasurer of the United States Transhumanist Party. Read more about him here

References

Tegmark, M. (2015). Elon Musk donates $10M to keep AI beneficial. Futureoflife.org. https://futureoflife.org/2015/10/12/elon-musk-donates-10m-to-keep-ai-beneficial/

Husain, A. (2018). Amir Husain: “The Sentient Machine: The Coming Age of Artificial Intelligence” | Talks at Google. Talks at Google. Youtube.com. https://www.youtube.com/watch?v=JcC5OV_oA1s&t=763s

Tegmark, M. (2017). Max Tegmark: “Life 3.0: Being Human in the Age of AI” | Talks at Google. Talks at Google. Youtube.com. https://www.youtube.com/watch?v=oYmKOgeoOz4&t=1208s

Conn, A. (2015). Pentagon Seeks $12 -$15 Billion for AI Weapons Research. Futureoflife.org. https://futureoflife.org/2015/12/15/pentagon-seeks-12-15-billion-for-ai-weapons-research/
BAI 2017 conference. (2017). ASILOMAR AI PRINCIPLES. Futureoflife.org. https://futureoflife.org/ai-principles/

Ng, A. (2017). Andrew Ng – The State of Artificial Intelligence. The Artificial Intelligence Channel. Youtube.com. https://www.youtube.com/watch?v=NKpuX_yzdYs

Bezos, J. (2017). Gala2017: Jeff Bezos Fireside Chat. Internet Association. Youtube.com. https://www.youtube.com/watch?v=LqL3tyCQ1yY

Schmidhuber, J. (2017). True Artificial Intelligence will change everything | Juergen Schmidhuber | TEDxLakeComo. TEDx Talks. Youtube.com. https://www.youtube.com/watch?v=-Y7PLaxXUrs

Kurzweil, R. (2001). The Law of Accelerating Returns. Kurzweil Accelerating Intelligence. Kurzweilai.net. http://www.kurzweilai.net/the-law-of-accelerating-returns

Sagan C. (1996). REMEMBERING CARL SAGAN. Charlierose.com. https://charlierose.com/videos/2625

Sbmadmin. (2008). Announcing the Science-Based Medicine Blog. Sciencebasedmedicine.org. https://sciencebasedmedicine.org/hello-world/

Zeb2-NAT Molecule May Reverse Cellular Aging – Article by Nicola Bagalà

Zeb2-NAT Molecule May Reverse Cellular Aging – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà explains a study that shows aged cells that usually resist reprogramming can be regenerated by reducing the level of Zeb2-NAT without harming the cells’ developmental potency.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 28, 2018

Researchers have found that by manipulating a single RNA molecule, they can reverse some aspects of cellular aging and regenerate aged cells.

Old cells resist regeneration

As we grow older, our cells gradually age, leading to the development of various diseases. Therefore, inducing cellular regeneration is one of the approaches that researchers are using to combat the age-related diseases associated with cellular aging. Unfortunately, aged cells are often highly resistant to therapies aimed at inducing regeneration.

Ribonucleic acid (RNA) is responsible for the creation of cellular proteins. However, a special type of molecule called non-coding RNA is never made into protein. In fact, when they mapped the human genome in 2001, they discovered that only around 2% of RNA is actually made into proteins.

Now, researchers have found a way to bypass the resistance of aged cells to being regenerated and becoming functionally more youthful.

What the study found out

In a recent Nature Communications paper, a team led by Dr. Bruno Bernardes de Jesus of the Instituto de Medicina Molecular (iMM) João Lobo Antunes in Lisboa discusses a technique that allowed the team to achieve easier cellular reprogramming of old fibroblasts into pluripotent cells [1].

Fibroblasts are connective tissue cells in animals that synthesize both the extracellular matrix, which is a “scaffolding” made up of extracellular molecules that provides structural and biochemical support to cells, and collagen, which is the main structural protein of connective tissues in animal bodies.

The study showed that the fibroblasts of old mice express higher levels of the transcription factor Zeb2. A transcription factor is a protein that regulates the DNA-to-messenger-RNA transcription rate, and Zeb2, in particular, induces epithelial cells to transition to mesenchymal cells. Epithelial cells are one of the four basic tissue types of animal cells, whereas mesenchymal cells are multipotent stem cells that give rise to fibroblasts, among others.

The synthesis of Zeb2 is controlled by the ribonucleic acid Zeb2-NAT (NAT stands for “natural antisense transcript”). What the scientists demonstrated in this paper is that by knocking down Zeb2-NAT in old mouse fibroblasts, Zeb2 can be downregulated significantly, which, in turn, leads to an enhanced fibroblast ability to turn into pluripotent cells rather than mesenchymal cells. The difference is that while mesenchymal cells can turn into only a certain range of related cells, pluripotent stem cells can turn into nearly all types of cells.

The way the researchers silenced Zeb2-NAT was by transfecting the fibroblasts with certain ribonucleic acid sequences—in other words, they introduced these sequences into the fibroblasts’ nuclei to modify their behavior.

Essentially, what they demonstrated is that aged cells that usually resist reprogramming can be regenerated by reducing the level of Zeb2-NAT without harming the cells’ developmental potency.

Conclusion

This study results spotlight the role of non-coding RNA in the fine-tuning and expression of protein-coding genes involved in pluripotency, differentiation, and reprogramming.

This opens the door for the regeneration of aged cells and tissues in an effort to prevent or reverse age-related diseases caused by cellular aging.

Literature

[1] Bernardes de Jesus, B., Pires Marinho, S., Barros, S., Sousa-Franco A., Alves-Vale, C., Carvalho, T., Carmo-Fonseca, M. (2018). Silencing of the lncRNA Zeb2-NAT facilitates reprogramming of aged fibroblasts and safeguards stem cell pluripotency. Nature Communications.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

World Health Organization Puts the Elderly Back in the Picture – Article by Elena Milova

World Health Organization Puts the Elderly Back in the Picture – Article by Elena Milova

Elena Milova


Editor’s Note: In this article, Miss Elena Milova explains the success the anti-aging community has had in influencing policy makers at the WHO in including several provisions related to aging, in their global strategy and action plans of the next decade. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 27, 2018

Not long ago, we wrote about some complications involving the WHO 13th programme of work. In the initial version of this document, developed by the WHO working group in November 2017, the problems of the elderly were nearly completely overlooked. The joint effort of our community helped to bring this critical flaw to public attention.

During the meeting of the working group, it was announced that 90% of the comments received by WHO (out of 400) pointed out the need to set healthy aging as one of the priorities of the new programme of work. However, we didn’t know if our demand to focus on the implementation of the global strategy and action plan on aging and health would be fulfilled.

The good news is that the new draft programme published on the WHO site on November 5th includes several provisions related to aging. Our community managed to persuade these global policymakers to implement all activities listed in the global strategy to help society prepare for the Decade of Healthy Aging (2020-2030). Let’s have a closer look at these provisions.

15. The foundation of WHO’s work is SDG 3: ensuring healthy lives and promoting well-being for all at all ages. WHO is an organization focused principally on promoting health rather than merely fighting disease, and especially on improving health among vulnerable populations and reducing inequities. Leaving no-one behind, the Organization aims to give women and men, girls and boys, in all social groups, the opportunity to live not just long but also healthy lives. WHO will explore measuring this foundation of its work using healthy life expectancy, which could serve as one overarching measure aligned with SDG 3, complemented by the triple billion goal, which leads to three more specific priorities, each with overlapping one-billion people goals.

Healthy life expectancy (HALE) is an assessment of the period of time a person can live in full health. HALE is usually lower than total life expectancy, and the difference between HALE and total life expectancy is regarded as years of life lost to disease.

As the goal of our community is to prolong the healthy period of life by addressing the root mechanisms of aging and postponing age-related disease, the introduction of HALE as a way to measure WHO activities is a very good outcome. It is very hard to preserve health in older ages without addressing the underlying mechanisms of aging and implementing an extensive program that involves educating the public about healthy lifestyles. This choice of indicator means that WHO will strengthen its efforts to keep people healthy for as long as possible, which will ease the introduction of rejuvenation interventions once they are available, as it will likely be a cost-effective way to achieve a more favorable HALE.

16. Life expectancy at birth has consistently increased since the 19th century, largely due to socioeconomic developments and public health measures such as vaccination, nutrition and
sanitation. Today, socioeconomic, political, cultural, environmental and economic forces continue to drive changes in the burden of disease. However, efforts are needed to ensure that their impact is positive. Poor health literacy coupled with weak health-promoting policies make it difficult for people to make healthy choices for themselves and their families. Investment in health promotion and disease prevention allows countries to address economic concerns about the rising costs of the health system and enables potential savings if disease can be avoided.

The WHO draft programme of work refers here to the increasing burden of chronic, non-communicable diseases due to the increasing proportion of people age 60 and over. Indeed, it would be really hard to double or even triple healthcare and pension expenditures for many countries, especially taking into account the ongoing economic crisis. However, this is what aging societies will have to do, if HALE does not grow faster.

This is why WHO is only promoting evidence-based interventions that represent the “best buy” scenarios: the most realistic and cost-effective. When it comes to age-related diseases, which can last 20-30 years or longer, prevention could be much cheaper, and it is more humane, as this scenario would reduce unnecessary human suffering. Therefore, we could consider this provision of the new draft programme as supporting our efforts to introduce longevity lifestyles and even “soft” (careful and evidence-based) biohacking.

17. Healthy life expectancy has not increased at the same pace as life expectancy, and increasing age often brings increasing morbidity and reduced functioning, making healthy ageing an important focus. Most disability-adjusted life years in older age are attributable to chronic conditions and the accumulated impact of such conditions can lead to significant loss in function and care dependence in older age. At the same time, there is emerging evidence that healthy ageing depends on early childhood development and is epigenetically determined. Ensuring healthy ageing is an urgent challenge in all countries.

This provision once again underlines how important it is to focus on prevention. I would like to point out that if childhood is perceived as the foundation of healthy lifestyles, longevity advocates receive carte blanche for working with the younger generation. Activists could think of developing corresponding education programs for schools and universities, and this very provision can be a strong argument when offering such a program to educational authorities.

37. Ensuring healthy ageing is central to universal health coverage, just as it is to the other priorities of GPW 13. The number of people over the age of 60 is expected to double by 2050 and this unprecedented demographic transition will require a radical societal response. The Secretariat will support Member States to promote healthy ageing through the actions defined by the Global strategy and action plan on ageing and health (2016), as well as through the Decade of Healthy Ageing that is planned for the period 2020−2030. These actions include aligning health systems to the needs of older populations, with a special focus on enhancing the functioning of older persons and the management of chronic disease; improving access to medicines; developing systems of longterm care including community-based services; promoting palliative care, creating age-friendly environments; and improving measurement, monitoring and understanding of healthy ageing.

This provision is exactly what we were aiming for when calling the members of our community to take part in the Open Consultation or the Draft. As you remember, all mentions of the WHO documents related to aging were absent; this provision clearly shows that we achieved our goal! Even though the global strategy and action plan on aging and health may not be ideal in terms of rejuvenation research promotion, it helps member states navigate the field with more confidence. This global strategy, which we wanted so much to be the foundation of the draft programme provisions related to aging, contains a very important paragraph that every activist should know about:

105. Finally, better clinical research is urgently needed on the etiology of, and treatments for, the key health conditions of older age, including musculoskeletal and sensory impairments, cardiovascular disease and risk factors such as hypertension and diabetes, mental disorders, dementia and cognitive declines, cancer, and geriatric syndromes such as frailty. This must include much better consideration of the specific physiological differences of older men and women and the high likelihood that they will be experiencing mutimorbidities. This could also be extended to include possible interventions to modify the underlying physiological and psychological changes associated with ageing.

Conclusion

Dear friends, this is a victory! Our community managed to influence policymakers of the highest level: the World Health Organization. We managed to ensure that the new programme of work considers aging and age-related diseases to be an important issue, and the resulting global strategy and action plan on aging and health is an effective guide to helping our society adapt to population aging.

In terms of advocacy, this is a complete victory, which shows two important things. First, when we join forces, we can influence global health policy at the highest level. Our community became stronger, and our voice is being heard! Second, this victory shows that dialogue with the UN and its institutions, including decision-makers in these agencies, is possible, and it goes in the directions that we need: more focus on prevention and more focus on public health education related to aging.

I offer special thanks to Dr. Ilia Stambler for initially turning the attention of the community to this issue. I want to thank and congratulate all participants of the Open Consultation with this achievement. Of course, we are still at the beginning of our path to rejuvenation as a public health priority, but outcomes like this one make me believe that there are more victories to come. Let’s keep working, as the main reward is worth it: health, youth, and freedom from age-related diseases for all!

About 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.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses an experimental drug, J147, for treating Alzheimer’s disease and also how Alzheimer’s disease is closely linked to aging.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 26, 2018

J147 is an experimental drug that has been shown to treat Alzheimer’s disease, and it also appears to reverse some aspects of aging. It is also poised to enter human clinical trials in the near future, although how it works has been somewhat of a puzzle.

A new study  published in the journal Aging Cell has changed all that, and the results are quite intriguing [1]. Researchers at the Salk Institute have solved the mystery of how J147 works and why it makes old flies, mice, and cells more youthful.

Rejuvenating mitochondria

The drug apparently works because it binds to a protein found in mitochondria, the powerhouses of cells; this, in turn, causes cells to function in a more youthful manner. Mitochondrial dysfunction is one of the hallmarks of aging and is thought to be a key reason why we age and develop age-related diseases [2]. This drug appears, at least partially, to address some of that dysfunction.

Finding the target of J147 was the key to revealing the link between Alzheimer’s disease and the aging process. It was the critical information the researchers needed and was holding the drug back from clinical trials.

Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory, and his team originally developed the J147 drug in 2011. The team screened numerous plant-sourced compounds with the potential to reverse the cellular and molecular signs of aging in the brain. The drug was developed as a modified version of a molecule found in the spice curcumin, a common ingredient in Asian foods such as curry.

Since then, the researchers have shown that J147 can reverse memory deficits, increases the production of brain cells, and slows the progression of Alzheimer’s in mice [3]. However, at that point, they did not understand how J147 worked.

Finding the target

During the new study lead by Dave Schubert and Salk Research Associate Josh Goldberg, the researchers used a number of approaches to find out how J147 worked. They eventually identified that the target of J147 was the mitochondrial protein known as ATP synthase, specifically ATP5A, a subunit of that protein. ATP synthase is involved in the mitochondrial generation of ATP, which cells use for energy.

The researchers demonstrated that by reducing the activity of ATP synthase, they were able to protect neuronal cells from a number of toxicities associated with the aging of the brain. One reason for this neuroprotective effect is thought to be the role of excitotoxicity in neuronal cell damage.

Excitotoxicity is the pathological process by which neurons are damaged and killed by the overactivation of receptors for the excitatory neurotransmitter glutamate. Think of it being a bit like a light switch being turned on and off so rapidly that it ends up causing the light bulb to blow.

Recently, the role of ATP synthase inhibition for neuroprotection against excitotoxic damage was demonstrated in a mouse study [4]. The second study showed that mouse models expressing the human form of mutant ATPase inhibitory factor 1 (hIF1), which causes a sustained inhibition of ATP synthase, were more resilient to neuronal death after excitotoxic damage. This data is consistent with this new J147 study, in which an increase in IF1 in the mice reduced the activity of ATP synthase (specifically ATP5A) and was neuroprotective.

ATP synthase is implicated in aging

ATP synthase has previously been shown to influence aging in C. elegans worms and flies. Given that aging is the greatest risk factor for developing Alzheimer’s disease, it is no surprise that the target of the drug is also involved in the aging process.

The team also revealed that by modulating the activity of ATP synthase, they could influence the levels of ATP and other molecules and were able to encourage healthier, more stable mitochondria during aging. Mice given the compound showed profound changes, appearing to look younger at a cellular and molecular level.

The researchers believe that these results are not only encouraging for the treatment of Alzheimer’s, they suggest that J147 may also be useful in treating other age-related diseases.

“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Dave Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”

With J147 having just completed the FDA required toxicology testing in animals, the next step is phase 1 human clinical trials, and the road to approval begins.

Conclusion

It is very heartening to hear important researchers suggesting that in order to treat age-related diseases, one needs to treat the aging processes themselves. This is the exactly what Dr. Aubrey de Grey and others have been saying for many years. It is good to hear more voices joining the call to tackle age-related diseases at their root: the hallmarks and damages where they all begin.

The process of age-related disease begins long before the familiar signs and diagnoses are made; by targeting the early processes that are not given specific disease names, we might yet defeat horrific diseases, such as Alzheimer’s, which rob us of who we are.

Literature

[1] Joshua Goldberg et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 2018 DOI: 10.1111/acel.12715
[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
[3] Prior, M., Dargusch, R., Ehren, J. L., Chiruta, C., & Schubert, D. (2013). The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer’s disease mice. Alzheimer’s research & therapy, 5(3), 25.
[4] Formentini, L., Pereira, M. P., Sánchez‐Cenizo, L., Santacatterina, F., Lucas, J. J., Navarro, C., … & Cuezva, J. M. (2014). In vivo inhibition of the mitochondrial H+‐ATP synthase in neurons promotes metabolic preconditioning. The EMBO journal, 33(7), 762-778.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Exercise is Currently the Best Way to Slow Down Aging – Article by Michael Falk

Exercise is Currently the Best Way to Slow Down Aging – Article by Michael Falk

Michael Falk


Editor’s Note: In this article, Mr. Michael Falk explains how exercising slows down aging. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 25, 2018

We have all heard that exercise is good for our health. However, it can not only keep you healthy, it can also slow down some aspects of aging. Some researchers even think that it might be possible to use this knowledge to develop new therapies against aging. While waiting for that to happen, we need to exercise in order to slow down the effects of aging.

How important is it to keep fit?

So, how beneficial is exercising? Well, one of the best studies conducted on this subject showed that women will live 5.6 years longer and men 6.2 years longer if they exercise between 1 and 2.5 hours per week [1]. This makes exercise a better lifestyle choice than any other, at least as long as you’re not counting avoiding downright dangerous behavior, such as smoking.

The main benefits of physical activity may come from better health for the heart. Exercise lessens the risk for many types of heart disease [2]. It is even more beneficial for people who already suffered age-related conditions, including stroke and coronary heart disease, and it is more effective than any known drug in preventing repeated episodes [3].

The key improvements also include increased muscle strength, stronger bones, better weight control, and improved cognitive function. This means less risk of age-related diseases, such as Alzheimer’s disease, as well as lethal falls, which are a major risk for the elderly.

The conclusion is that exercise helps with a lot of different aspects of your health in several ways, and we can summarize its effects as improving quality of life and increasing healthspan.

How much exercise do you need?

More exercise does not always improve outcomes. Professional athletes exercise more than the rest of us, and they generally live longer than the average person [4]. However, correlation isn’t causation, and robust individuals are perhaps more likely to become athletes, instead of the other way around. There could even be negative effects from too much exercise, although that is far from certain.

Even moderate exercise leads to better health. Half an hour a day seems to be enough to see positive effects, and it is also a common recommendation for the minimum amount of exercise you should get. The biggest difference can be seen between people who hardly move around at all and people who get at least a little exercise a few times a week. Taking the stairs and walking short distances is clearly better than nothing. In fact, some studies show that even light activity, such as housework, can have an effect on mortality risk.

It should also be noted that there are different types of exercise and that these could have different benefits. Jogging increases your aerobic ability, which should, among other things, lead to better heart health. Lifting weights is an anaerobic exercise that improves strength and should bring other benefits, such as stronger bones. A lot of research about this has been done already, but so far, we don’t definitively know the optimal amount and type of training for each particular type of person.

Drugs to mimic exercise

Some of the positive effects have to do with the anti-inflammatory processes that occur when exercising [5]. Other mechanisms appear to be involved, although more research on these mechanisms is needed.

Since the advantages of exercise are clear, the idea has occurred to some researchers that it may be possible to mimic the effects of exercise without doing the hard work and getting sweaty. Research is now being conducted using drugs that target the same mechanisms to try to get the same benefits of exercise.

This typically involves adjusting a part of the human metabolism, which is not an easy matter. However, there have been at least some tentative breakthroughs already, and last year, a team found a drug that boosted the endurance of mice by roughly 70 percent [6]. Where this might lead in the future is not clear, but some positive effects may come from this research.

Will exercise lead to longevity?

Even though exercise is beneficial for your health, there is no guarantee it will keep you alive until you reach 100, although staying fit will almost certainly improve your chances. This is why if we want to remain in good health and live longer, we need to develop rejuvenation biotechnology and therapies that address the aging processes directly. That said, if you want to increase your chances of living long enough to see these therapies arrive, then exercise is the best option you have right now.

Literature

[1] Schnohr, P., Lange, P., Scharling, H., & Jensen, J. S. (2006). Long-term physical activity in leisure time and mortality from coronary heart disease, stroke, respiratory diseases, and cancer. The Copenhagen City Heart Study. European Journal of Cardiovascular Prevention & Rehabilitation, 13(2), 173-179.

[2] Jakovljevic, D. G. (2017). Physical activity and cardiovascular aging: Physiological and molecular insights. Experimental Gerontology.

[3] Naci, H., & Ioannidis, J. P. (2013). Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. Bmj, 347, f5577.

[4] Lemez, S., & Baker, J. (2015). Do elite athletes live longer? a systematic review of mortality and longevity in elite athletes. Sports medicine-open, 1(1), 16.

[5] Fan, W., Waizenegger, W., Lin, C. S., Sorrentino, V., He, M. X., Wall, C. E., … & Auwerx, J. (2017). PPARδ Promotes Running Endurance by Preserving Glucose. Cell Metabolism, 25(5), 1186-1193.

[6] Dimitrov, S., Hulteng, E., & Hong, S. (2017). Inflammation and exercise: Inhibition of monocytic intracellular TNF production by acute exercise via β 2-adrenergic activation. Brain, behavior, and immunity, 61, 60-68.

About Michael Falk

Michael Falk is a communication specialist with 15 years of experience writing about healthcare and technology. He has been an advocate of longevity research since 2013, when he started his longevity blog Unggamma (www.unggammal.se).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.