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Why I Hope to Be Alive at 75 – Article by Steve Hill

Why I Hope to Be Alive at 75 – Article by Steve Hill

U.S. Transhumanist Party Logo

Steve Hill


Editor’s Note: In this article, originally published on November 13, 2020, by our allies at the Life Extension Advocacy Foundation (LEAF), Steve Hill explains why the attitude of Joe Biden’s new advisor on COVID-19 strategy, Ezekiel Emanuel, is supremely counterproductive. Emanuel infamously wrote in 2014 that he hopes to die at age 75. Given that COVID-19 is a disease whose toll is greatly amplified by biological aging, Emanuel’s statements render him uniquely ill-suited  to remedy the ravages of the ongoing pandemic. Moreover, his pessimism toward what life is like at age 75 is no longer justified, in light of emerging medical advances that could enable rejuvenation and biological youthfulness for those who are in late middle age today. Perhaps, if he sees these advances become a reality in the not-too-distant future, Emanuel might change his mind regarding the desirability of longer lifespans.

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, November 17, 2020


2020 has been a strange year for a variety of reasons, but the societal changes that the COVID-19 pandemic has created are probably the strangest. However, it is perhaps even stranger that Dr. Ezekiel Emanuel has been appointed to advise Joe Biden on COVID strategy.

Emanuel is best known for writing a controversial article in the October 2014 edition of The Atlantic, headlined “Why I Hope to Die at 75”, in which he strongly rejects the desire to live beyond the age of 75 and expresses his opinion that continuing to live after such an age is meaningless.

Living too long is also a loss. It renders many of us, if not disabled, then faltering and declining, a state that may not be worse than death but is nonetheless deprived.

Needless to say, I strongly disagree with this baffling point of view and am somewhat concerned that someone who thinks this way of his own life, and presumably the lives of others, may be appointed to a position of influence for a disease whose primary risk group is the elderly. This seems almost as foolhardy as spending a vacation weekend in a caravan with Hannibal Lecter.

Emanuel listed quite a few methods by which people extend their lives and stated that they were a “valiant effort to cheat death and prolong life as long as possible,” but his response to them was, “I reject this aspiration. I think this manic desperation to endlessly extend life is misguided and potentially destructive.”

Age is the #1 risk factor for COVID

The scientific evidence clearly shows that the primary risk factor for contracting and dying from COVID-19 is age, with people over the age of 75 at particularly high risk. This is due to the decline of the immune system, which becomes increasingly weak and dysfunctional with age in a process known as immunosenescence.

Globally, the strategy has been to try to shield these vulnerable people as best as possible due to their weakened immune systems and limit their exposure to the disease while vaccines are developed.

Needless to say, I find Biden’s nomination of him to address a disease that mostly affects seniors ironic in itself, given that he thinks the lives of most people beyond 75 are pointless and that they don’t live meaningful lives and would be better off embracing death rather than desperately trying to extend them. Therefore, I hope for the sake of the older people in our society that he has rethought his priorities.

Why I hope to be alive at 75

Predictably, there is already a storm raging on social media around his appointment, so there is no purpose to adding more fuel to that fire. Instead, I am going to talk about why the future of aging could be very different to the grim picture that Emanuel paints.

At age 63, he is getting closer to the age at which he thinks life is pointless, and I believe that a large reason why he is so pessimistic about life beyond 75, whether he realizes it or not, is based on the current state of medicine. This line of reasoning does not take into account how medicine, and in particular how we treat aging could change in the next decade or two.

Current medicine does a great job at keeping people alive for longer, but they often have to live with one or more chronic diseases. Given that, I am not surprised that Emanuel is not enamored with living a long life, especially as that could entail being disabled, bed-bound, or otherwise suffering a poor quality of life as the result of debilitating age-related diseases.

Thankfully, the world healthcare strategy is slowly starting to shift to one of prevention over cure, but right now, the typical approach is to play whack-a-mole with diseases. As one pops up, it is treated, then the next, and the next, and so on. This strategy works great for infectious diseases, but it is an exercise in futility and diminishing returns when applied to the chronic diseases of aging.

However, things could be different in the not so distant future, and being 75 could see the majority of people far more fit, healthy, and vibrant than ever before in human history thanks to advances in aging research. Therapies that directly target aging could potentially make people biologically younger (in particular their immune systems) and much more able to withstand COVID-19 and other diseases.

As explained on LEAF’s What is Aging? page, aging consists of multiple processes (“hallmarks”) that gradually cause damage to organs and tissues and lead to age-related diseases. Rejuvenation biotechnology is advanced medical technology that directly addresses any of the various aging processes in order to restore tissue and organ function to a more youthful state, thereby ameliorating, delaying, or preventing age-related diseases. Let’s take a brief look at some of the promising near-future research that could bear fruit by the time Emanuel reaches 75 and perhaps change his mind.

Rejuvenating the immune system

The decline of the immune system is a key reason why the elderly are most susceptible to infectious diseases such as COVID, and there has been considerable interest in the rejuvenation of the immune system in recent years.

Dr. Greg Fahy from intervene immune has had some early success with thymus rejuvenation in a small human pilot study and demonstrated that it is possible to cause the thymus, which shrinks and loses its capacity to produce immune T cells during aging, to regrow and resume production of those cells. Dr. Fahy is now moving forward into a larger-scale study, and if the results continue to be positive, it is not hard to imagine that thymus regrowth could become a staple of helping the elderly stay healthy.

Another example of immune rejuvenation is currently being developed by Samumed, a biotechnology company that is developing drugs that target the Wnt pathway to restore it to youthful function. The Wnt pathway is a key pathway that regulates the function of our stem cells and ensures that they supply our tissues and organs with new cells to replace losses from injury, disease, and wear and tear.

If successful, this approach would allow the body to resume efficient repair of tissues, and it would replenish aged and failing tissues and organs with fresh, healthy cells supplied by the rejuvenated stem cells.

Therapeutic plasma exchange

Researchers Irina and Mike Conboy at UC Berkeley have been researching blood factors and their role in aging for over two decades. During that time, they have identified a number of factors present in aged blood that appear to regulate aging.

These factors are also present in younger people, but in typically far lower amounts, and tend to serve useful functions. However, during aging, the levels of these proteins become deregulated, and they often rise to detrimental levels and cause damage to the body, which typically involves preventing stem cells from working and tissue from regenerating.

Decades’ worth of research from the Conboy lab has shown that, in mice at least, it is possible to filter out these harmful pro-aging blood factors and bring them back down to a level similar to younger animals. When this happens, the result is rejuvenation of tissues and the reversal of some of the aspects of aging, making the mice more youthful.

This approach uses an already approved technique known as therapeutic plasma exchange to filter and calibrate these key factors and could be readily modified for human use. Should the results seen in animals translate to humans using this approach, it would have a profound effect on our health as we age and potentially delay, prevent, or even reverse some age-related diseases.

Conclusion

These are only some of the examples of why healthy life expectancy could rise significantly in the near future, and there are plenty of reasons to remain future positive. This is the future direction of medicine and healthcare that we support at Lifespan.io, a world where being 75 does not mean you are thrown on the scrap heap and where people like Emanuel will no longer feel that life has no meaning. I am confident that in such a world, being 75 would not be the burden he thinks it will be, and this is why I hope to be alive at 75.

Steve Hill serves on the Life Extension Advocacy Foundation (LEAF) Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, along with attending various medical industry conferences. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration, which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.

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.