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Remembering the Man Who Turned Numbers Into Hope – Article by Steven Horwitz and Sarah Skwire

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Categories: Economics, Education, Tags: , , , , , , , , ,

The New Renaissance HatSteven Horwitz and Sarah Skwire
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After the spate of celebrities who died in 2016, the death of a Swedish professor of international health might not seem very newsworthy. However, Hans Rosling, who died of pancreatic cancer on February 7th, was no ordinary or obscure professor.

The story of his life and career can be found both at Wikipedia and in this marvelous Nature profile. What those sources cannot quite convey is Rosling’s importance as a role model for intellectual honesty, personal warmth and charisma, and a willingness to go where the facts took him, regardless of whether those facts adhered to any simplistic political narrative of humanity’s past and future. Both Rosling’s intellectual fearlessness and the substance of his work have importance for those who care about human freedom and progress.

Intellect and Humanity

But it isn’t just the content of Rosling’s work that matters. He was an amazing rhetorician. He had a unique ability to use and present data in easy to understand and visually appealing ways that were very effective at conveying an argument. He also was able to think creatively about the linkages among the various causes of wealth and the improvements they made in human well-being. His natural storytelling ability gave him the capacity to put those complex historical factors into narratives that not only got the history right, but did so in a way that appealed to our shared humanity.

All of these skills are on display in his two most famous videos, both of which impart lessons in presenting ideas and interpretations of data that classical liberals will find very useful.

Underlying much of Rosling’s work as a public intellectual was a concern with how we enable all of humanity to share in the health and wealth that has come to characterize the Western world.

With his background in health and demographics, Rosling was interested in the factors that led to the rising health and longevity of the West. First, of course, he had to document just how much better things had become in the West, then he had to explore the causes.

Presenting the raw data about the improvement of the West was the centerpiece of his BBC video “200 Years, 200 Countries, 4 Minutes.” Using real-time data visualization techniques, he shows how every country in the world was poor and sick 200 years ago and then showed the path by which so many countries became wealthy and healthy. There is no better visualization of the progress of humanity than this one.

For those of us who work with students, this video gives us the opportunity to talk about the factors that made that growth happen, including the role of liberal institutions and the rising moral status of the individual in that process. It is a great complement to the work of Deirdre McCloskey.

The video also provides a way to talk about global inequality. What is clear from the visualization of the data is that 200 years ago, countries were far more equal than now, but they were equally poor.

It’s true that the gap between rich and poor countries is greater now than back then, but everyone has improved their absolute position. And two of the countries that have improved the most are two of the most populous: China and India. Rosling’s presentation opens up countless useful discussions of the importance of economic growth for increases in life expectancy, as well as what exactly concerns us about growing inequality.

As he concludes, the task before us now is to figure out how to bring the rest of the world up to where the West is. Though he does not discuss it, the economic evidence is clear that those countries that have experienced the most growth, and therefore the biggest increases in longevity and other demographic measures of well-being, are those that have the freest economies. By giving us the data, Rosling enables classical liberals to engage the conversation about the “why” and “how” of human betterment.

Inspirational ‘Edutainer’

But our favorite video of Rosling’s is definitely “The Magic Washing Machine.” Here Rosling uses the example of the washing machine to talk about economic growth and its ability to transform human lives for the better.

Rosling’s focus is on the way the washing machine is an indicator of a population that has grown wealthy enough not only to buy such machines, but also to provide the electricity to power them. The washing machine is a particularly valuable machine since it relieves most of the physical burden of one of the most onerous tasks of the household, and one that has historically fallen entirely to women.

No one who has seen the video can forget the story of Rosling’s grandmother pulling up a chair in front of the new washing machine for the sheer joy of sitting and watching while the clothes spin. Her excitement becomes even more poignant when one considers that this must have been the first time in her life when she was able to sit while laundry was done, instead of standing over a tub of hot water and soap.

Rosling points out, in a moment of calling his fellow progressives to task, that while many of his students are proud of biking to class instead of driving, none of them do their wash by hand. That chore, though green, is simply too onerous for most moderns to take on. He then goes on to discuss how we have to find ways to create the energy needed as billions of people cross the “wash line” and start to demand washing machines.

The video ends with him reaching into the washing machine and pulling out the thing that the machine really made possible:  books. The washing machine gave his mother time to read and to develop herself, as well as to read to young Hans and boost his education as well.

The visual image of putting clothes into a washing machine and pulling out books in exchange captures all that is good about economic growth in a succinct and unforgettable way. Rosling concludes the video with a heart-felt roll call of gratitude to industrialization and development that has been known to reduce free market economists to tears.

What Rosling does in that video is to effectively communicate what classical liberals see as the real story of economic growth. He gets us to see how economic growth, driven by markets, has enabled women to live more liberated lives. Classical liberals can talk endlessly about the data, but until we talk effectively about the way in which industrialization and markets have made it possible for women (and others) to be freed from drudgery that was literally back-breaking, we cannot win the war on the market.

Thank You

Bastiat said that “The worst thing that can happen to a good cause is, not to be skillfully attacked, but to be ineptly defended.” Hans Rosling’s work is the best possible example of the best kind of defense of a good cause. He was a model and an inspiration.

Rosling ends “The Magic Washing Machine” by saying “Thank you industrialization. Thank you steel mill. Thank you power station. And thank you chemical processing industry that gave us time to read books.”

We say, “Thank you, Dr. Rosling. Thank you, data visualization. Thank you TED talks. And thank you, Mrs. Rosling, for buying a washing machine and reading to your son.” We are richer for the work he did. We are poorer for his loss.

Steven Horwitz is the Charles A. Dana Professor of Economics at St. Lawrence University and the author of Hayek’s Modern Family: Classical Liberalism and the Evolution of Social Institutions. He is spending the 2016-17 academic year as a Visiting Scholar at the John H. Schnatter Institute for Entrepreneurship and Free Enterprise at Ball State University.

He is a member of the FEE Faculty Network.

Sarah Skwire is the Literary Editor of FEE.org and a senior fellow at Liberty Fund, Inc. She is a poet and author of the writing textbook Writing with a Thesis. She is a member of the FEE Faculty Network. Email

This article was published by The Foundation for Economic Education and may be freely distributed, subject to a Creative Commons Attribution 4.0 International License, which requires that credit be given to the author. Read the original article.

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UNITY Biotechnology Raises $116M for Senescent Cell Clearance Development – Article by Reason

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Categories: Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , ,

The New Renaissance HatReason
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The whispers of late have had it that UNITY Biotechnology was out raising a large round of venture funding, and their latest press release shows that this was indeed the case. The company, as you might recall, is arguably the more mainstream of the current batch of startups targeting the clearance of senescent cells as a rejuvenation therapy. The others include Oisin Biotechnologies, SIWA Therapeutics, and Everon Biosciences, all with different technical approaches to the challenge. UNITY Biotechnology is characterized by a set of high profile relationships with noted laboratories, venture groups, and big names in the field, and, based on the deals they are doing, appear to be focused on building a fairly standard drug development pipeline: repurposing of apoptosis-inducing drug candidates from the cancer research community to clear senescent cells, something that is being demonstrated with various drug classes by a range of research groups of late. Senescent cells are primed to apoptosis, so a nudge in that direction provided to all cells in the body will have little to no effect on normal cells, but tip a fair proportion of senescent cells into self-destruction. Thus the UNITY Biotechnology principals might be said to be following the standard playbook to build the profile of a hot new drug company chasing a hot new opportunity, and clearly they are doing it fairly well so far.

UNITY Biotechnology Announces $116 Million Series B Financing

Quote:

UNITY Biotechnology, Inc. (“UNITY”), a privately held biotechnology company creating therapeutics that prevent, halt, or reverse numerous diseases of aging, today announced the closing of a $116 million Series B financing. The UNITY Series B financing ranks among the largest private financings in biotech history and features new investments from longtime life science investors ARCH Venture Partners, Baillie Gifford, Fidelity Management and Research Company, Partner Fund Management, and Venrock. Other investors include Bezos Expeditions (the investment vehicle of Jeff Bezos) and existing investors WuXi PharmaTech and Mayo Clinic Ventures. Proceeds from this financing will be used to expand ongoing research programs in cellular senescence and advance the first preclinical programs into human trials.

The financing announcement follows the publication of research that further demonstrates the central role of senescent cells in disease. The paper, written by UNITY co-founders Judith Campisi and Jan van Deursen and published today, describes the central role of senescent cells in atherosclerotic disease and demonstrates that the selective elimination of senescent cells holds the promise of treating atherosclerosis in humans. In animal models of both early and late disease, the authors show that selective elimination of senescent cells inhibits the growth of atherosclerotic plaque, reduces inflammation, and alters the structural characteristics of plaque such that higher-risk “unstable” lesions take on the structural features of lower-risk “stable” lesions. “This newly published work adds to the growing body of evidence supporting the role of cellular senescence in aging and demonstrates that the selective elimination of senescent cells is a promising therapeutic paradigm to treat diseases of aging and extend healthspan. We believe that we have line of sight to slow, halt, or even reverse numerous diseases of aging, and we look forward to starting clinical trials with our first drug candidates in the near future.”

So this, I think, bodes very well for the next few years of rejuvenation research. It indicates that at least some of the biotechnology venture community understands the likely true size of the market for rejuvenation therapies, meaning every human being much over the age of 30. It also demonstrates that there is a lot of for-profit money out there for people with credible paths to therapies to treat the causes of aging. It remains frustrating, of course, that it is very challenging to raise sufficient non-profit funds to push existing research in progress to the point at which companies can launch. This is a problem throughout the medical research and development community, but it is especially pronrounced when it comes to aging. The SENS view of damage repair, which has long incorporated senescent cell clearance, is an even tinier and harder sell within the aging research portfolio – but one has to hope that funding events like this will go some way to turn that around.

From the perspective of being an investor in Oisin Biotechnologies, I have to say that this large and very visible flag planted out there by the UNITY team is very welcome. The Oisin team should be able to write their own ticket for their next round of fundraising, given that the gene therapy technology they are working on has every appearance of being a superior option in comparison to the use of apoptosis-inducing drugs: more powerful, more configurable, and more adaptable. When you are competing in a new marketplace, there is no such thing as too much validation. The existence of well-regarded, well-funded competitors is just about the best sort of validation possible. Well-funded competitors who put out peer-reviewed studies on a regular basis to show that the high-level approach you and they are both taking works really well is just icing on the cake. Everyone should have it so easy. So let the games commence! Competition always drives faster progress. Whether or not I had skin in this game, it would still be exciting news. The development of rejuvenation therapies is a game in which we all win together, when new treatments come to the clinic, or we all lose together, because that doesn’t happen fast enough. We can and should all of us be cheering on all of the competitors in this race. The quality and availability of the outcome is all that really matters in the long term. Money comes and goes, but life and health is something to be taken much more seriously.

Now with all of that said, one interesting item to ponder in connection to this round of funding for UNITY is the degree to which it reflects the prospects for cancer therapies rather than the prospects for rejuvenation in the eyes of the funding organizations. In other words, am I being overly optimistic in reading this as a greater understanding of the potential for rejuvenation research in the eyes of the venture community? It might be the case that the portions of the venture community involved here understand the market for working cancer drugs pretty well, and consider that worth investing in, with the possibility of human rejuvenation as an added bonus, but not one that is valued appropriately in their minds. Consider that UNITY Biotechnology has partnered with a noted cancer therapeutics company, and that the use of drugs to inducing apoptosis is a fairly well established approach to building cancer treatments. That is in fact why there even exists a range of apoptosis-inducing drugs and drug candidates for those interested in building senescent cell clearance therapies to pick through. Further, the presence of large numbers of senescent cells does in fact drive cancer, and modulating their effects (or removing them) to temper cancer progress is a topic under exploration in the cancer research community. So a wager on a new vision, or a wager on the present market? It is something to think about.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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It’s Time to Postpone Your Appointment with the Grim Reaper – Article by Gerrard Jayaratnam

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Categories: Philosophy, Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance HatGerrard Jayaratnam
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How long would you like to live for? Is there a limit to how long we can live for? These are not questions you hear often, but do not be surprised if they are repeated more frequently in the future. The reason? Life extension. It is the concept of living well beyond the average lifespan. [1]

Humans are already living longer due to vaccines and improvements in sanitation. [2] The World Health Organization reported that the average life expectancy at birth increased from 48 years in 1955 to 65 years in 1995, and is projected to rise to 73 years by 2025. [3] As medical techniques continue to improve, we are more inclined than ever to pursue life extension. [1] Indeed, from the Epic of Gilgamesh to China’s First Emperor, prolonging life has been an ever-present thought in society. [4, 5] Both individuals failed to escape death, but the idea of life extension ironically lives on. Even so, is it truly possible and what should upcoming doctors and scientists consider if they are to join the most ambitious of quests?

The “Horcruxes” of reality 

In the fictional Harry Potter series, “Horcruxes” were objects where people could hide a fragment of their soul in an attempt to take one step towards immortality. [6] Of course, humans cannot split their souls and hide them in objects, but there are several proposed means by which life extension may be achieved. [1] This is a testimony to the progress within the life extension field, but there remains much room for improvement.

Eat less, live more

Caloric restriction (CR) is one proposed method for life extension. [1] In the CALERIE (Comprehensive Assessment of Long term Effects of Reducing Intake of Energy) trial, 218 non-obese humans were randomised to either a control group or an intervention group. The latter aimed for a 25% reduction from baseline energy intake. At the end of the 2-year study period, the intervention group had significantly greater reductions in circulating levels of TNF-α – an inflammatory marker involved in many age-related diseases. [7] Dr Alexander Miras, winner of the 2014 Nutrition Society Cuthbertson Medal for his research on bariatric surgery, acknowledges that the study was a “good first step,” but argues that “the evidence in humans is lacking.” “A definitive RCT (randomised controlled trial),” Dr Miras continues, “would be very hard, if not impossible.” He also spots a glaring consequence of CR. “My personal approach is to avoid caloric restriction as this leads to hunger which is an unpleasant feeling. I would rather live a shorter life, but enjoy my food.”

Manipulating telomerase

One alternative is modulating telomerase activity – as attempted with the anti-ageing TA-65MD® supplement. [8] Telomeres protect the ends of chromosomes [9]; they resemble the aglets on the ends of shoelaces. Just as shoelaces would unravel without the aglet, chromosomes would lose vital DNA sequences in the absence of telomeres. [9] Our cells divide over time, causing telomeres to shorten. Once the telomere becomes too short, cell division ceases, and short telomeres correlate with cellular ageing. [10] Telomerase is an enzyme that can oppose telomere shortening [10] – it was what Hamlet was to King Claudius; what exercise is to obesity; and what junior doctors, in England, will be to Jeremy Hunt.

Reactivating telomerase in telomerase-deficient mice reversed both neurodegeneration and degeneration of other organs. [11] This proved the concept that boosting telomerase activity could have anti-ageing effects, but there is little proof that this occurs in humans. While the mice were telomerase-deficient, humans normally have some telomerase activity. It is like giving food to someone who has been fasting for hours and to someone who has just eaten a three-course meal – the starved individual would unquestionably benefit more. A 12-month long RCT, involving 117 relatively healthy individuals (age range: 53-87), found that low-dose TA-65 significantly increased telomere length when compared to placebo. High-dose TA-65, however, failed to do so. [12]

Dancing with the devil

What is more worrying than treatments that may be ineffective? Side effects. Telomerase is a double-edged sword and by reducing telomere attrition, it can promote unlimited cell division and cancer. [9] Elizabeth Blackburn, co-winner of the 2009 Nobel Prize in Physiology or Medicine for her role in the discovery of telomerase, has doubts about exploiting the enzyme. Speaking to TIME magazine, she said, “Cancers love telomerase, and a number of cancers up-regulate it like crazy. . . . My feeling would be that if I take anything that would push my telomerase up, I’m playing with fire.” [13]

A cauldron of rewards

CR and boosting telomerase activity are just a small sample of life extending techniques, yet there is the notion that such techniques will be intertwined with risks. However, risks are always weighed against rewards, and Gennady Stolyarov, editor-in-chief of The Rational Argumentator and Chief Executive of the Nevada Transhumanist Party, believes life extension would bring “immense and multifaceted” rewards. “The greatest benefit is the continued existence of the individual who remains alive. Each individual has incalculable moral value and is a universe of ideas, experiences, emotions, and memories. When a person dies, that entire universe is extinguished . . . This is the greatest possible loss, and should be averted if at all possible.” Stolyarov also envisages “major savings to healthcare systems” and that “the achievement of significant life extension would inspire many intelligent people to try to solve other age-old problems.”

Former chairman of the President’s Council on Bioethics, Leon Kass, disagrees with this view and argues that mortality is necessary for “treasuring and appreciating all that life brings.” [14] Hence, increased longevity could lead to an overall reduction in productivity over one’s lifetime. Perhaps Kass is correct, but the array of potential benefits makes it seem unwise to prematurely dismiss life extension. In fact, a survey, which examined the opinions of 605 Australians on life extension, highlighted further benefits – 23% of participants said they could “spend more time with family” and 4% cited the opportunity to experience future societies. [15]

Learning from our mistakes

Conversely, life extension may result in people enduring poor health for longer periods. 28% of participants in the Australian survey highlighted this concern. [15] Current trends in life expectancy reinforce their fears. Professor Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham, explains, “Currently, in most countries in the developed world, life expectancy is increasing at approximately 2 years per decade, but healthspan (the years spent in good health) is only increasing at 1.7 years. This has major consequences . . . as more of later life is spent in poor health.” This is a consequence of treating “killer diseases” – according to Dr Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging. “The current model in biomedicine,” says Dr Sierra, “is to treat one disease at a time. Let’s imagine you have arthritis; cancer; and are starting to develop Alzheimer’s disease. So what do we do? We treat you for cancer. You now live longer with Alzheimer’s disease and arthritis.” A better approach is clear to Dr Sierra who stresses the importance of compression of morbidity – “the goal is to live longer with less time spent being sick.”

Learning from our successes

Even with Dr Sierra’s approach, individual boredom and social implications, including overpopulation, would still be problems.[16] According to Stolyarov, the boredom argument does not hold up when facing “human creativity and discovery.” He believes humans could never truly be bored as “the number of possible pursuits increases far faster than the ability of any individual to pursue.”

In his novel Death is Wrong, Stolyarov explained that the idea that society could not cope with a rapidly expanding population was historically inaccurate. The current population “is the highest it has ever been, and most people live far longer, healthier, prosperous lives than their ancestors did when the Earth’s population was hundreds of times smaller.” [16] If it has been achieved in the past, who is to say our own society – one far more advanced than any before it – cannot adapt?

The verdict

Life extension research is quietly progressing, and there is a good chance that it will eventually come to fruition. Although there are doubts about current techniques, Dr Sierra draws attention to novel interventions, such as rapamycin, which “delay ageing in mice.” He concludes that the next challenge is to “develop measures than can predict whether an intervention works in a short-term assay.” Such measures would provide the scaffolding for future clinical trials that test life extension techniques.

Given what may be gained, it is no surprise that artificially prolonging life is exciting some in the same way the Tree of Knowledge tempted Eve. The impact on society? Impossible to predict. It would undoubtedly be a big risk, but perhaps in this complex and uncertain scenario, we ought to remember the words of the poet Thomas Stearns Eliot: “Only those who will risk going too far can possibly find out how far one can go.” [17]

Gerrard Jayaratnam is a student of Biomedical Science at Imperial College London.

References

  1. Stambler I. A History of Life-Extensionism in the Twentieth Century. Ramat Gan: CreateSpace Independent Publishing Platform; 2014.
  2. National Institute on Aging. Living Longer. 2011. https://www.nia.nih.gov/research/publication/global-health-and-aging/living-longer.
  3. World Health Organization. 50 Facts: Global Health situation and trends 1955-2025. 2013. http://www.who.int/whr/1998/media_centre/50facts/en/.
  4. Encyclopaedia Britannica. Epic of Gilgamesh. 2016. http://www.britannica.com/topic/Epic-of-Gilgamesh.
  5. Lloyd DF. The Man Who Would Cheat Death and Rule the Universe. Vision. 2008. http://www.vision.org/visionmedia/history-shi-huang-emperor-china/5818.aspx.
  6. Rowling JK. Harry Potter and the Half-Blood Prince. London: Bloomsbury Publishing; 2005.
  7. Ravussin E, Redman LM, Rochon J, et al. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci 2015;70:1097-1104.
  8. A. Sciences. What is TA-65®? (n.d.) [Accessed 3rd April 2016]. https://www.tasciences.com/what-is-ta-65/.
  9. De Jesus BB, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet 2013;29:513-520.
  10. A. Sciences. Telomeres and Cellular Aging. (n.d.) [Accessed 3rd April 2016]. https://www.tasciences.com/telomeres-and-cellular-aging/.
  11. Jaskelioff M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase deficient mice. Nature 2011;469:102-106.
  12. Salvador L, Singaravelu G, Harley CB, et al. A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study. Rejuvenation Res 2016; ahead of print. doi:10.1089/rej.2015.1793.
  13. Kluger J. The antiaging power of a positive attitude. TIME. 2015.
  14. Than K. The Psychological Strain of Living Forever. Live Science. 2006. http://www.livescience.com/10469-psychological-strain-living.html.
  15. Partridge B, Lucke J, Bartlett H, et al. Ethical, social, and personal implications of extended human lifespan identified by members of the public. Rejuvenation Res 2009;12:351-357.
  16. Stolyarov II G. Death is Wrong. 2nd ed. Carson City, Nevada: Rational Argumentator Press; 2013.
  17. The Huffington Post. 11 Beautiful T.S. Eliot Quotes. 2013. http://www.huffingtonpost.com/2013/09/26/ts-eliot-quotes_n_3996010.html.

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The Two Faces of Aging: Cancer and Cellular Senescence – Article by Adam Alonzi

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Categories: Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance Hat
Adam Alonzi
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This article is republished with the author’s permission. It was originally posted on Radical Science News.

hELA-400x300Multiphoton fluorescence image of HeLa cells.

Aging, inflammation, cancer, and cellular senescence are all intimately interconnected. Deciphering the nature of each thread is a tremendous task, but must be done if preventative and geriatric medicine ever hope to advance. A one-dimensional analysis simply will not suffice. Without a strong understanding of the genetic, epigenetic, intercellular, and intracellular factors at work, only an incomplete picture can be formed. However, even with an incomplete picture, useful therapeutics can be and are being developed. One face is cancer, in reality a number of diseases characterized by uncontrolled cell division. The other is degradation, which causes a slue of degenerative disorders stemming from deterioration in regenerative capacity.

Now there is a new focus on making geroprotectors, which are a diverse and growing family of compounds that assist in preventing and reversing the unwanted side effects of aging. Senolytics, a subset of this broad group, accomplish this feat by encouraging the removal of decrepit cells. A few examples include dasatinib, quercetin, and ABT263. Although more research must be done, there are a precious handful of studies accessible to anyone with the inclination to scroll to the works cited section of this article. Those within the life-extension community and a few enlightened souls outside of it already know this, but it bears repeating: in the developed world all major diseases are the direct result of the aging process. Accepting this rather simple premise, and you really ought to, should stoke your enthusiasm for the first generation of anti-aging elixirs and treatments. Before diving into the details of these promising new pharmaceuticals, nanotechnology, and gene therapies we must ask what is cellular senescence? What causes it? What purpose does it serve?

Depending on the context in which it is operating, a single gene can have positive or negative effects on an organism’s phenotype. Often the gene is exerting both desirable and undesirable influences at the same time. This is called antagonistic pleiotropy. For example, high levels of testosterone can confer several reproductive advantages in youth, but in elderly men can increase their likelihood of developing prostate cancer. Cellular senescence is a protective measure; it is a response to damage that could potentially turn a healthy cell into a malignant one. Understandably, this becomes considerably more complex when one is examining multiple genes and multiple pathways. Identifying all of the players involved is difficult enough. Conboy’s famous parabiosis experiment, where a young mouse’s system revived an old ones, shows that alterations in the microenviornment, in this case identified and unidentified factors in the blood of young mice, can be very beneficial to their elders. Conversely, there is a solid body of evidence that shows senescent cells can have a bad influence on their neighbors. How can something similar be achieved in humans without having to surgically attach a senior citizen to a college freshman?

By halting its own division, a senescent cell removes itself as an immediate tumorigenic threat. Yet the accumulation of nondividing cells is implicated in a host of pathologies, including, somewhat paradoxically, cancer, which, as any life actuary’s mortality table will show, is yet another bedfellow of the second half of life. The single greatest risk factor for developing cancer is age. The Hayflick Limit is well known to most people who have ever excitedly watched the drama of a freshly inoculated petri dish. After exhausting their telomeres, cells stop dividing. Hayflick et al. astutely noted that “the [cessation of cell growth] in culture may be related to senescence in vivo.” Although cellular senescnece is considered irreversible, a select few cells can resume normal growth after the inactivation of the p53 tumor suppressor. The removal of p16, a related gene, resulted in the elimination of the progeroid phenotype in mice. There are several important p’s at play here, but two are enough for now.

Our bodies are bombarded by insults to their resilient but woefully vincible microscopic machinery. Oxidative stress, DNA damage, telomeric dysfunction, carcinogens, assorted mutations from assorted causes, necessary or unnecessary immunological responses to internal or external factors, all take their toll. In response cells may repair themselves, they may activate an apoptotic pathway to kill themselves, or just stop proliferating. After suffering these slings and arrows, p53 is activated. Not surprisingly, mice carrying a hyperactive form of p53 display high levels of cellular senescence. To quote Campisi, abnormalities in p53 and p15 are found in “most, if not all, cancers.” Knocking p53 out altogether produced mice unusually free of tumors, but those mice find themselves prematurely past their prime. There is a clear trade-off here.

In a later experiment Garcia-Cao modified p53 to only express itself when activated. The mice exhibited normal longevity as well as an“unusual resistance to cancer.” Though it may seem so, these two cellular states are most certainly not opposing fates. As it is with oxidative stress and nutrient sensing, two other components of senescence or lack thereof, the goal is not to increase or decrease one side disproportionately, but to find the correct balance between many competing entities to maintain healthy homeostasis. As mentioned earlier, telomeres play an important role in geroconversion, the transformation of quiescent cells into senescent ones. Meta-analyses have shown a strong relationship between short telomeres and mortality risk, especially in younger people. Although cancer cells activate telomerase to overcome the Hayflick Limit, it is not entirely certain if the activation of telomerase is oncogenic.

majormouse

SASP (senescence-associated secretory phenotype) is associated with chronic inflammation, which itself is implicated in a growing list of common infirmities. Many SASP factors are known to stimulate phenotypes similar to those displayed by aggressive cancer cells. The simultaneous injection of senescent fibroblasts with premalignant epithelial cells into mice results in malignancy. On the other hand, senescent human melanocytes secrete a protein that induces replicative arrest in a fair percentage of melanoma cells. In all experiments tissue types must be taken into account, of course. Some of the hallmarks of inflammation are elevated levels of IL-6, IL-8, and TNF-α. Inflammatory oxidative damage is carcinogenic and an inflammatory microenvironment is a good breeding ground for malignancies.

Caloric restriction extends lifespan in part by inhibiting TOR/mTOR (target of rapamycin/mechanistic target of rapamycin, also called  the mammalian target of rapamycin). TOR is a sort of metabolic manager, it receives inputs regarding the availability of nutrients and stress levels and then acts accordingly. Metformin is also a TOR inhibitor, which is why it is being investigated as a cancer shield and a longevity aid. Rapamycin has extended average lifespans in all species tested thus far and reduces geroconversion. It also restores the self-renewal and differentiation capacities of haemopoietic stem cells. For these reasons the Major Mouse Testing Program is using rapamycin as its positive control. mTOR and p53 dance (or battle) with each other beautifully in what Hasty calls the “Clash of the Gods.” While p53 inhibits mTOR1 activity, mTOR1 increases p53 activity. Since neither metformin nor rapamycin are without their share of unwanted side effects, more senolytics must be explored in greater detail.

Starting with a simple premise, namely that senescent cells rely on anti-apoptotic and pro-survival defenses more than their actively replicating counterparts, Campisi and her colleagues created a series of experiments to find the “Achilles’ Heel” of senescent cells. After comparing the two different cell states, they designed senolytic siRNAs. 39 transcripts were selected for knockdown by siRNA transfection, and 17 affected the viability of their target more than healthy cells. Dasatinib, a cancer drug, and quercitin, a common flavonoid found in common foods, have senolytic properties. The former has a proven proclivity for fat-cell progenitors, and the latter is more effective against endothelial cells. Delivered together, they they remove senescent mouse embryonic fibroblasts. Administration into elderly mice resulted in favorable changes in SA-BetaGAL (a molecule closely associated with SASP) and reduced p16 RNA. Single doses of D+Q together resulted in significant improvements in progeroid mice.

If you are not titillated yet, please embark on your own journey through the gallery of encroaching options for those who would prefer not to become chronically ill, suffer immensely, and, of course, die miserably in a hospital bed soaked with several types of their own excretions―presumably, hopefully, those who claim to be unafraid of death have never seen this image or naively assume they will never be the star of such a dismal and lamentably “normal” final act. There is nothing vain about wanting to avoid all the complications that come with time. This research is quickly becoming an economic and humanitarian necessity. The trailblazers who move this research forward will not only find wealth at the end of their path, but the undying gratitude of all life on earth.

Adam Alonzi is a writer, biotechnologist, documentary maker, futurist, inventor, programmer, and author of the novels “A Plank in Reason” and “Praying for Death: Mocking the Apocalypse”. He is an analyst for the Millennium Project, the Head Media Director for BioViva Sciences, and Editor-in-Chief of Radical Science News. Listen to his podcasts here. Read his blog here.

References

Blagosklonny, M. V. (2013). Rapamycin extends life-and health span because it slows aging. Aging (Albany NY), 5(8), 592.

Campisi, Judith, and Fabrizio d’Adda di Fagagna. “Cellular senescence: when bad things happen to good cells.” Nature reviews Molecular cell biology 8.9 (2007): 729-740.

Campisi, Judith. “Aging, cellular senescence, and cancer.” Annual review of physiology 75 (2013): 685.

Hasty, Paul, et al. “mTORC1 and p53: clash of the gods?.” Cell Cycle 12.1 (2013): 20-25.

Kirkland, James L. “Translating advances from the basic biology of aging into clinical application.” Experimental gerontology 48.1 (2013): 1-5.

Lamming, Dudley W., et al. “Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity.” Science 335.6076 (2012): 1638-1643.

LaPak, Kyle M., and Christin E. Burd. “The molecular balancing act of p16INK4a in cancer and aging.” Molecular Cancer Research 12.2 (2014): 167-183.

Malavolta, Marco, et al. “Pleiotropic effects of tocotrienols and quercetin on cellular senescence: introducing the perspective of senolytic effects of phytochemicals.” Current drug targets (2015).

Rodier, Francis, Judith Campisi, and Dipa Bhaumik. “Two faces of p53: aging and tumor suppression.” Nucleic acids research 35.22 (2007): 7475-7484.

Rodier, Francis, and Judith Campisi. “Four faces of cellular senescence.” The Journal of cell biology 192.4 (2011): 547-556.

Salama, Rafik, et al. “Cellular senescence and its effector programs.” Genes & development 28.2 (2014): 99-114.

Tchkonia, Tamara, et al. “Cellular senescence and the senescent secretory phenotype: therapeutic opportunities.” The Journal of clinical investigation 123.123 (3) (2013): 966-972.

Zhu, Yi, et al. “The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs.” Aging cell (2015).

 

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BioViva Treats First Patient with Gene Therapy to Reverse Aging – Press Release by Elizabeth Parrish

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Categories: Announcements, Science, Transhumanism, Tags: , , , , , , , , , , , ,

The New Renaissance HatElizabeth Parrish
October 3, 2015
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BioViva USA, Inc. has become the first company to treat a person with gene therapy to reverse biological aging, using a combination of two therapies developed and applied outside the United States of America. Testing and research on these therapies is continuing in BioViva’s affiliated labs worldwide.

BioViva CEO Elizabeth Parrish announced that the subject is doing well and has resumed regular activities. Preliminary results will be evaluated at 5 and 8 months with full outcome expected at 12 months. The patient will then be monitored every year for 8 years.

Gene therapy allows doctors to treat disease at the cellular level by inserting a gene into a patient’s cells instead of using the regular modalities of oral drugs or surgery. BioViva is testing several approaches to age reversal, including using gene therapy to introduce genes into the body.

Although not generally considered a disease, cellular aging is the leading cause of death in the developed world. Side effects like muscle wasting (sarcopenia), grey hair and memory loss are the well-known hallmarks.

And the aging cell is also responsible for the diseases of aging, including Alzheimer’s disease, heart disease and cancer. BioViva is leading the charge to treat the aging cell and reverse aging. “The aging cell is a key factor that has been overlooked for too long. Companies have put millions of dollars into treating the diseases of aging, such as dementia, frailty, kidney failure and Parkinson’s disease, and we still do not have a cure,” says Parrish.

Until now, no company had tried multiple gene therapies in one person. When asked why BioViva has done so, Parrish says, “Aging involves multiple pathways. We wanted to target more than one for a better outcome.”

Contact
Elizabeth Parrish
lparrish(at)BioVivaSciences(dot)com
http://www.biovivasciences.com

Elizabeth Parrish, CEO of BioViva, is a humanitarian, entrepreneur, and innovator, and is a leading voice for genetic cures. As a strong proponent of progress and education for the advancement of regenerative medicine modalities, she serves as a motivational speaker to the public at large for the life sciences. She is actively involved in international educational media outreach and sits on the board of the International Longevity Alliance (ILA). She is an affiliated member of the Complex Biological Systems Alliance (CBSA), which is a unique platform for Mensa-based, highly gifted persons who advance scientific discourse and discovery.

The mission of the CBSA is to further scientific understanding of biological complexity and the nature and origins of human disease. Elizabeth is the founder of BioTrove Investments LLC and the BioTrove Podcasts, which is committed to offering a meaningful way for people to learn about and fund research in regenerative medicine.  She is also the Secretary of The American Longevity Alliance (ALA), a 501(c)(3) nonprofit trade association that brings together individuals, companies, and organizations who work in advancing the emerging field of cellular and regenerative medicine.

Editor’s Note: Elizabeth Parrish also made the announcement of this promising human trial at the October 1, 2015, Movement for Indefinite Life Extension (MILE) panel discussion “How Can Life Extension Become as Popular as the War on Cancer?” Watch the discussion here.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, October 3, 2015

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How Can Life Extension Become as Popular as the War on Cancer? – MILE Panel

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Categories: Philosophy, Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , , , ,

MILE-Demonstration-2-Ad

What can be done to raise public support for the pursuit of indefinite life extension through medicine and biotechnology to the same level as currently exists for disease-specific research efforts aimed at cancers, heart disease, ALS, and similar large-scale nemeses?

In this panel discussion, which occurred on October 1, 2015 – International Longevity Day – Mr. Stolyarov asks notable life-extension supporters to provide input on this vital question and related areas relevant to accelerating the pursuit of indefinite longevity. Watch the full discussion here.

This panel is coordinated in conjunction with MILE, the Movement for Indefinite Life Extension.

View the presentation slides prepared by Sven Bulterjis, “Aging Research Needs Marketing: What Can We Learn from Cancer Research?”:

Download the PDF version.
Download the Microsoft PowerPoint version.
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Also see a statement prepared by Peter Rothman for this event. This statement was read out by Mr. Stolyarov during the panel, and panelists’ responses were solicited.

Read the announcement by Keith Comito – “The #LifespanChallenge Starting on October 1 – International Longevity Day”.

See Mr. Comito’s introductory video for the Lifespan Challenge.

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Panelists

Adam Alonzi is the author of the fiction books “Praying for Death: A Zombie Apocalypse“and “A Plank in Reason”. He is also a futurist, inventor, DIY enthusiast, biotechnologist, programmer, molecular gastronomist, consummate dilletante and columnist at The Indian Economist. Listen to his podcasts at http://adamalonzi.libsyn.com/. Read his blog at https://adamalonzi.wordpress.com/.

Sven Bulterjis is a founder and member of the Board of Directors of Heales – the Healthy Life Extension Society, based in Brussels, Belgium. He has worked as a post-graduate researcher at the SENS Research Foundation and at Yale University. Moreover, he is an Advisor for the Lifeboat Foundation’s A-Prize, whose purpose is to put the development of artificial life forms into the open.

Keith Comito is a computer programmer and mathematician whose work brings together a variety of disciplines to provoke thought and promote social change. He has created video games, bioinformatics programs, musical applications, and biotechnology projects featured in Forbes and NPR.

In addition to developing high-profile mobile applications such as HBO Now and MLB AtBat, he explores the intersection of technology and biology at the Brooklyn community lab Genspace where he helped to create games which allow players to direct the motion of microscopic organisms. Read his Forbes article “Biological Games“.

Seeing age-related disease as one of the most profound problems facing humanity, he now works to accelerate and democratize longevity research efforts through initiatives such as Lifespan.io.
He earned a B.S. in Mathematics, B.S. in Computer science, and M.S. in Applied Mathematics at Hofstra University, where his work included analysis of the LMNA protein.

Roen Horn is a philosopher and lecturer on the importance of trying to live forever. He founded the Eternal Life Fan Club in 2012 to encourage fans of eternal life to start being more strategic with regard to this goal. To this end, one major focus of the club has been on life-extension techniques, everything from lengthening telomeres to avoiding risky behaviors. Currently, Roen’s work may be seen in the many memes, quotes, essays, and video blogs that he has created for those who are exploring their own thoughts on this, or who want to share and promote the same things. Like many other fans of eternal life, Roen is in love with life, and is very inspired by the world around him and wants to impart in others the same desire to discover all this world has to offer.

B.J. Murphy is the Editor and Social Media Manager of Serious Wonder. He is a futurist, philosopher, activist, author and poet. B.J. is an Advisory Board Member for the NGO nonprofit Lifeboat Foundation and a writer for the Institute for Ethics and Emerging Technologies (IEET).

Elizabeth Parrish, CEO of BioViva, is a humanitarian, entrepreneur, and innovator, and is a leading voice for genetic cures. As a strong proponent of progress and education for the advancement of regenerative medicine modalities, she serves as a motivational speaker to the public at large for the life sciences. She is actively involved in international educational media outreach and sits on the board of the International Longevity Alliance (ILA). She is an affiliated member of the Complex Biological Systems Alliance (CBSA), which is a unique platform for Mensa-based, highly gifted persons who advance scientific discourse and discovery.

The mission of the CBSA is to further scientific understanding of biological complexity and the nature and origins of human disease. Elizabeth is the founder of BioTrove Investments LLC and the BioTrove Podcasts, which is committed to offering a meaningful way for people to learn about and fund research in regenerative medicine.  She is also the Secretary of The American Longevity Alliance (ALA), a 501(c)(3) nonprofit trade association that brings together individuals, companies, and organizations who work in advancing the emerging field of cellular and regenerative medicine.

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Aging Research Needs Marketing: What Can We Learn from Cancer Research? – Presentation by Sven Bulterjis

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Categories: Science, Transhumanism, Tags: , , , , , , , , , , , , , ,

The New Renaissance HatSven Bulterjis
October 1, 2015
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These presentation slides were prepared by Sven Bulterjis and are a component of the materials for the October 1, 2015, Movement for Indefinite Life Extension (MILE) Panel: “How Can Life Extension Become as Popular as the War on Cancer?” The panel took place from 11 a.m. to 1 p.m. US Pacific Time on October 1, 2015. Watch the recording of the discussion, including Mr. Bulterjis’s presentation, here.
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Download the PDF version.
Download the Microsoft PowerPoint version.
***
Sven Bulterjis is a founder and member of the Board of Directors of Heales – the Healthy Life Extension Society, based in Brussels, Belgium. He has worked as a post-graduate researcher at the SENS Research Foundation and at Yale University. Moreover, he is an Advisor for the Lifeboat Foundation’s A-Prize, whose purpose is to put the development of artificial life forms into the open.

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The Plasticity of Aging and Longevity Continues – Article by Reason

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Categories: Science, Transhumanism, Tags: , , , , , , , , , , , ,

The New Renaissance Hat
Reason
December 4, 2014
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When looking at most of the past extension of human life since the 1700s the major causes were better sanitation and control of infectious disease, with the largest effects on life expectancy at birth arising from lowered childhood mortality, even though there was also a steady increase in adult life expectancy. When looking back at the late 20th and early 21st century period from a safe distance of a century or so, the similar high level summary of the drivers of life extension will probably focus on greatly increased control over cardiovascular disease and the resulting steep decline in late life mortality due to this cause. There are many other improvements in medicine that have occurred in the past fifty years, but this is the one that stands out if you look at the data.

This period of medical strategy and development is coming to an end, however, and the summary of the next age in medicine with regard to its effects on human longevity will be that this was the time in which researchers started to directly address the processes of aging and, separately, brought cancer largely under medical control. Progress in the future of life expectancy at this point in time is overwhelmingly a matter of success in intervening in the aging process, building biotechnologies to repair the cellular and molecular damage that causes aging and thus prevent or turn back age-related frailty and disease.

If aging is purely a matter of damage we should expect all improvements in long-term health to also extend life to some degree. If there is less damage then the machinery lasts longer – it really is that simple a concept, even though the machinery of our biology is very complex. Studies of changing life expectancy such as the one quoted below continue to find that aging appears to be plastic, and that present trends in reduced old age mortality are continuing in those regions with better access to medical technology. The only limits on life are imposed by a present inability to fix the problems that kill us, and that can be changed by funding the right research:

Quote:

In high-income countries, life expectancy at age 60 years has increased in recent decades. Falling tobacco use (for men only) and cardiovascular disease mortality (for both men and women) are the main factors contributing to this rise. In high-income countries, avoidable male mortality has fallen since 1980 because of decreases in avoidable cardiovascular deaths. For men in Latin America, the Caribbean, Europe, and central Asia, and for women in all regions, avoidable mortality has changed little or increased since 1980. As yet, no evidence exists that the rate of improvement in older age mortality (60 years and older) is slowing down or that older age deaths are being compressed into a narrow age band as they approach a hypothesised upper limit to longevity.

Link: http://dx.doi.org/10.1016/S0140-6736(14)60569-9

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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Global Cancer Scare – Article by Bradley Doucet

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Categories: Science, Tags: , , , , , , ,

The New Renaissance Hat
Bradley Doucet
December 29, 2013
Recommend this page.
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The coverage of the World Health Organization’s latest data on global cancer rates in today’s Globe and Mail was typical of the media in general: “the disease tightened its grip in developing nations struggling to treat an illness driven by Western lifestyles.” And a glance at the WHO’s GLOBOCAN Cancer Fact Sheet maps seems to confirm that “Western lifestyles” are the culprit, since living in a wealthier part of the world increases your risk of getting cancer. But what’s wrong with this picture?
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The main problem is that it makes it sound as if life in developing nations is getting worse as it becomes more like life in the wealthier parts of the world. This is pure hogwash. The WHO’s own data shows that life expectancy at birth rose from 2000 to 2011 in all regions of the world. Globally, it rose from 66 to 70 years; in Africa, from 50 to 56. People may be dying more than they used to from various cancers, but they’re clearly dying less from other causes, and the one more than makes up for the other.

Don’t get me wrong: Helping people afflicted with cancer in poorer parts of the world is a fine thing to do. But the best way to help in the long run is to help them get richer so they can help themselves. This undoubtedly would make them even more like us in terms of “lifestyle” and would undoubtedly lead to even higher rates of cancer. But it would also lead to less dying from other causes, and longer life expectancy overall. I’m willing to bet that’s a trade every person living in the developing world would be happy to make.

Bradley Doucet is Le Québécois Libre‘s English Editor and the author of the blog Spark This: Musings on Reason, Liberty, and Joy. A writer living in Montreal, he has studied philosophy and economics, and is currently completing a novel on the pursuit of happiness. He also writes for The New Individualist, an Objectivist magazine published by The Atlas Society, and sings.

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A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

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Categories: Science, Technology, Tags: , , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance Hat
Reason
October 6, 2012
Recommend this page.
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A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.

While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:

1) Destruction of Senescent Cells

Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.

The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.

2) Selective Pruning and Support of the Immune System

One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.

Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient’s immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells – or more adventurous processes such as cultivating thymic cells in a patient’s lymph nodes.

3) Mitochondrial Repair

Our mitochondria sabotage us. There’s a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.

There are any number of proposed methods for dealing with this component of the aging process – either repairing or making it irrelevant – and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising.

Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

4) Reversing Stem Cell Aging

The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.

Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell – and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.

Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations – and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date – a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.

The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.

Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.

5) Clearing Advanced Glycation Endproducts (AGEs)

AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.

Now on the one hand it seems to be the case that one particular type of AGE – glucosepane – makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven’t made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.

This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.

6) Clearing Aggregates and Lysomal Garbage

All sorts of aggregates build up within and around cells as a result of normal metabolic processes, causing harm as they grow, and the sheer variety of these waste byproducts is the real challenge. They range from the amyloid that features prominently in Alzheimer’s disease through to the many constituents of lipofuscin that clog up lysosomes and degrade cellular housekeeping processes. At this point in the advance of biotechnology it remains the case that dealing with each of the many forms of harmful aggregate must be its own project, and so there is a great deal of work involved in moving from where we stand today to a situation in which even a majority of the aggregates that build up with age can be removed.

The most promising lines of research to remove aggregates are immunotherapy, in which the immune system is trained or given the tools to to consume and destroy a particular aggregate, and medical bioremediation, which is the search for bacterial enzymes that can be repurposed as drugs to break down aggregates within cells. Immunotherapy to attack amyloid as a treatment for Alzheimer’s is a going concern, for example. Biomedical remediation is a younger and far less funded endeavor, however.

My expectation here is that some viable therapies for some forms of unwanted and harmful metabolic byproducts will emerge in the laboratory over the next decade, but that will prove to be just the start on a long road indeed. From here it’s hard for me to guess at where the 80/20 point might be in clearing aggregates: successfully clearing the five most common different compounds? Or the ten most common? Or twenty? Lipofuscin alone has dozens of different constituent chemicals and proteins, never mind the various other forms of aggregate involved in specific diseases such as Alzheimer’s.

But work is work: it can be surmounted. Pertinently, and again, the dominant issue in timing here is the lack of funding and support for biomedical remediation and similar approaches to clearing aggregates.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

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