How will we defeat aging? Scientific debate ends with surprising verdict, signaling new investment opportunities

SAN FRANCISCO, June 10, 2024 – A landmark debate titled "How to Defeat Aging," held at the Foresight Institute on May 27, 2024, produced an unexpected winner, uncovering a far more nuanced narrative behind the recent surge of interest to rejuvenation biotechnology. The event pitted two leading scientists against each other, each offering contrasting perspectives on the future of aging research. 

The debate was organized by Open Longevity, a nonprofit working on the development of effective and affordable solutions to the aging problem for the benefit of all humanity. The idea of the new format was proposed by Misha Batin from Open Longevity, and the event is planned as one of a series of public debates designed to put the spotlight on unresolved questions and the most important scientific disagreements with the goal of accelerating progress.

Dr. Aubrey de Grey, president and chief science officer of the Longevity Escape Velocity (LEV) Foundation, a renowned advocate for rejuvenation therapies, passionately argued that aging is a process caused by accumulated damage, which could potentially be repaired through targeted interventions. His SENS (Strategies for Engineered Negligible Senescence) proposal has become and remains the rallying cry for the emerging biotech industry developing a comprehensive set of therapies with the aim of periodic repair of various types of age-related damage, envisioning the possibility of radical life extension and the delaying age-related diseases. 

Dr. Peter Fedichev, CEO of Gero.ai, one of the thought leaders in longevity and another proponent of radical biotech solutions to the aging problem, who applies quantitative models of human aging, challenged de Grey’s optimistic view on rejuvenation. Dr. Fedichev emphasized the inherent limitations posed by the stochastic (random) and thermodynamically irreversible nature of human aging. 

Dr. Fedichev instead presented a strong case about the limitations of even the best experimental approaches for human rejuvenation, suggesting it might offer only around 10-15 additional years of lifespan at best. According to Fedichev, with current technologies, we have the potential to double our lifespan—or even live for hundreds of years—by focusing on halting aging instead, following the inspiring examples of negligibly senescent animals, including mammals such as naked mole rats and some species of bats. 

Achieving this goal, however, will require completely different therapeutic targets, drugs, and biomarkers than those used by most of the longevity industry to achieve rejuvenation effects. Gero is developing therapy aimed to halt aging. Dr. Fedichev’s position is based on his Theory of Aging, presented in a series of publications starting from 2015,^[1][2][3] and confirmed and developed by the subsequent research by Gero and other scientists^{[4][5][6][7][8][9]} (2024).

The debate, which was judged by prominent academic experts and live streamed on YouTube, captivated the onsite audience for nearly three hours. When the debate concluded, the jury declared Dr. Fedichev the winner — albeit by a narrow margin of 42 to 38 points. He was awarded the cash prize of $10,000.

“To defeat aging, we need to understand what aging is. A bad theory is better than no theory since a bad theory may still provide you with interesting edge cases—possible experiments leading to its own invalidation and hence to a better theory with even more challenging edge cases,” said Dr. Peter Fedichev. “People often say aging needs its Manhattan or Apollo project. The truth is that both kinds of projects got underway after scientists mastered the underlying theories so well that they were able to estimate the parameters—from masses and sizes to timelines and costs—with no more than one order of magnitude error. Aging will be stopped only when our theoretical understanding matches this level.”

“I greatly enjoyed debating the feasibility of radical life extension with Peter Fedichev. Our discussion highlighted the urgent need for more experiments to determine the reversibility of information-based aging, such as epigenetic noise,” said Dr. Aubrey de Grey.

This debate aimed to spark a renewed discussion within the scientific community and the public sphere regarding the most promising strategies for addressing the challenges and opportunities presented by an aging population. As the field of longevity research continues to evolve, this debate serves as a crucial milestone, highlighting the complexities and nuances of this critical area of scientific inquiry.

The argument presented by Dr. Aubrey de Grey

Aubrey de Grey argued in favor of the feasibility and potential of rejuvenation therapies to reverse aging and achieve radical life extension. His key points included

1. Aging is a phenomenon caused by the accumulation of various types of molecular and cellular damage over time. This damage is theoretically repairable through the development of comprehensive rejuvenation therapies targeting each specific form of damage.
2. He outlined his SENS (Strategies for Engineered Negligible Senescence) approach, which identifies seven major categories of aging damage and proposes potential therapies to periodically repair or remove that damage. This includes addressing issues like cell loss, nuclear mutations, mitochondrial mutations, and other biological processes.
3. De Grey argued that once these rejuvenation therapies are developed and applied periodically, they could allow people to maintain a physiological age of around 25 indefinitely, thereby escaping age-related diseases and achieving radical life extension.
4. He cited the rapid progress in fields like gene therapy, stem cell therapy, and other regenerative medicine approaches as evidence that the required therapies for rejuvenation are becoming increasingly feasible.
5. De Grey challenged the notion that “informatic" aspects of aging will make radical life extension impossible in the near future, arguing that nearly all such information can be recovered by existing methods.
6. He emphasized the importance of pursuing rejuvenation research more aggressively, as even modest progress could significantly extend the healthy human lifespan and alleviate suffering caused by age-related diseases.

In summary, Aubrey de Grey's main argument centered around the idea that aging is a phenomenon caused by accumulated damage that can be repaired through the development of comprehensive rejuvenation therapies, potentially allowing for radical life extension and the indefinite postponement of age-related diseases.

The argument presented by Dr. Peter Fedichev

Peter Fedichev argued that aging in humans is not a single process with a definite set of regulators that could be used as therapeutic targets. Instead, it is a compound effect of a very large number of independent microscopic failures and as such is stochastic (random) and thermodynamically irreversible. If this is true, it imposes significant limitations on the potential effectiveness of rejuvenation therapies. His key points included:

1. Stochastic Nature of Aging: Fedichev emphasized that aging is driven by random (stochastic) independent microscopic processes that lead to the accumulation of damage over time. This randomness and overwhelming quantity of manifestations of aging makes it inherently difficult to predict and control the aging process through targeted interventions. 
2. Thermodynamic Irreversibility: He argued that certain types of damage associated with aging are thermodynamically irreversible, meaning that they cannot be fully repaired or reversed without achieving full control over all molecular processes in the body, which we are very far from technologically. This challenges the notion that comprehensive rejuvenation therapies can turn aging around.
3. Limitations of Rejuvenation Therapies: Fedichev suggested that while rejuvenation therapies demonstrated so far might offer some benefits, they are unlikely to achieve radical life extension. He estimated that such therapies might only extend human lifespan by around 10-15 years at best, due to the inherent limitations imposed by the stochastic and irreversible nature of aging.
4. Focus on Practical Interventions: He advocated for a more pragmatic approach to aging research, focusing on the development of interventions that can prevent irreversible damage and thereby slow down or even halt human aging. This is, according to Fedichev, the only realistic approach that may yield dramatic life extension in our species with the technology we already have.
5. Importance of Understanding Aging Mechanisms: Fedichev highlighted the need for a deeper understanding of the fundamental mechanisms driving aging. He called for developing a theory of aging up to standards attained in physical and engineering sciences and argued that without this level of understanding, it is challenging to develop effective interventions that can significantly impact the aging process.

In summary, Peter Fedichev's main arguments centered around the idea that aging is driven by stochastic and thermodynamically irreversible processes, which impose significant limitations on the potential effectiveness of rejuvenation therapies. He advocated for a more pragmatic and yet comparatively radical approach to life-extension, aiming at slowing down and or even halting human aging to achieve negligible senescence of the type already known to nature and demonstrated by negligibly senescent animals. If we could halt aging at the point where the likelihood of dying each year is the same as that of a 40-year-old in developed countries (0.5% annually), the expected remaining lifespan would be 200 years.

More details about the contestants, their background, research pipeline, positions, and contributions are available on the Open Longevity website.

“The battle against aging hinges significantly on funding, controlled by those who allocate it. Currently, many donors have their own 'pocket' scientists, pushing their viewpoints while hindering others from receiving essential funds,” said Misha Batin, CEO and co-founder of Open Longevity. “At the same time, for years, various theories of aging have coexisted peacefully, with proponents publishing papers, receiving grants, starting companies, and maintaining cordial relationships. However, we now face a postmodern situation where gerontologists rarely critique each other's approaches, leading to a stagnation in progress. Open debate is crucial to addressing these critical questions, setting future research trends, and helping develop effective solutions. Radical differences in opinion present opportunities for breakthroughs. This is why we propose organizing dozens of public debates. By making the fight against aging more transparent, we hope to elevate the Longevity field and accelerate progress in the fight against death.”

Where to learn more about the debate

• Playback of the debate, along with a transcript is here.
• An edited version of the debate, with the speakers’ presentation material, is here. 
• Photos of the event are here.

About Open Longevity

Based in Silicon Valley, Open Longevity is a community-driven organization dedicated to extending human life through rigorous scientific research and innovative technology. Our work spans multiple initiatives, including the Open Genes Database, which aids researchers in understanding the genetic factors of aging and SayForever!, a global campaign advocating for a future free from aging. We also manage First Approval, a secure platform that accelerates scientific discoveries by enabling seamless data sharing among researchers. Our projects are supported by collaborations with leading scientists and institutions worldwide, aiming to transform the approach to age-related diseases and life extension. Open Longevity's mission is to challenge the conventional views on aging, promoting a future where radical life extension becomes commonplace. To join us in redefining the boundaries of human lifespan, visit openlongevity.org.

About Gero

Based in Silicon Valley, Gero is a preclinical-stage drug discovery company with research and development operations in Singapore and Europe. Gero leverages complex systems physics, generative AI, extensive medical records (over 10 million), genotypes, and rich molecular data to train a large health model (LHM) and develop therapies targeting aging and age-related diseases. The company’s unique approach unites complex dynamic systems physics with advanced generative AI to revolutionize drug discovery, emphasizing the irreversible nature of aging while identifying top targets for transformative therapies. Gero made several critical discoveries in aging and drug discovery, and its published articles have been covered in Science, Nature Communications, Scientific American, and Popular Mechanics. Gero is using its drug discovery platform for in-house projects and in collaborations with pharmaceutical companies, including one with Pfizer. Gero collaborates with top-tier researchers from institutions such as Harvard Medical School, MIT, and the National University of Singapore. The company has developed the world’s first mRNA anti-aging vaccine, based on its successful rejuvenation experiments in mice, and has identified transformative "pipeline-in-a-pill" targets across 40 disease clusters. To learn more, visit Gero.ai.

About Longevity Escape Velocity Foundation

The Longevity Escape Velocity (LEV) Foundation exists to conduct and inspire research to proactively identify and address the most challenging obstacles on the path to the widespread availability of comprehensively effective treatments to prevent and reverse human age-related disease. LEV is conducting and funding various initiatives like Robust Mouse Rejuvenation study, the first attempt to detect synergistic benefits of various combinations of treatments, each of which has existing evidence suggesting the potential to extend healthy lifespans;  Transplants on Demand, - vitrification technology to enable true "off-the-shelf" organ replacement and several advocacy & education initiatives. To learn more, visit levf.org.

About the Foresight Institute

Foresight Institute is a research organization and non-profit that supports the beneficial development of high-impact technologies. Since our founding in 1986 on a vision of guiding powerful technologies, we have continued to evolve into a many-armed organization that focuses on several fields of science and technology that are too ambitious for legacy institutions to support. From molecular nanotechnology to brain-computer interfaces, space exploration, crypto-commerce, and AI, Foresight gathers leading minds to advance research and accelerate progress toward flourishing futures. To learn more, visit foresight.org.

^[1] Critical dynamics of gene networks is a mechanism behind ageing and Gompertz law D. Podolskiy, I. Molodtcov, A. Zenin, et al arXiv:1502.04307v2 (2015) [q-bio.MN]

^[2] Pyrkov, T.V., Avchaciov, K., Tarkhov, A.E. et al. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Nat Commun 12, 2765 (2021). https://doi.org/10.1038/s41467-021-23014-1

^[3] Avchaciov, K., Antoch, M.P., Andrianova, E.L. et al. Unsupervised learning of aging principles from longitudinal data. Nat Commun 13, 6529 (2022). https://doi.org/10.1038/s41467-022-34051-9

^[4] Aging clocks, entropy, and the limits of age-reversal | bioRxiv

^[5] Tarkhov, A.E., Lindstrom-Vautrin, T., Zhang, S. et al. Nature of epigenetic aging from a single-cell perspective. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00616-0

^[6] Tong, H., Dwaraka, V.B., Chen, Q. et al. Quantifying the stochastic component of epigenetic aging. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00600-8

^[7] Meyer, D.H., Schumacher, B. Aging clocks based on accumulating stochastic variation.Nat Aging (2024). https://doi.org/10.1038/s43587-024-00619-x

^[8] Peter Niimi, Victoria Gould, Kyra Thrush-Evensen, Morgan E. Levine. The Latent Aging of Cells bioRxiv 2024.05.28.596284; doi: https://doi.org/10.1101/2024.05.28.596284

^[9] Differential Responses of Dynamic and Entropic Aging Factors to Longevity Interventions, Kristina Perevoshchikova,, Peter O. Fedichev. bioRxiv 2024.02.25.581928; doi: https://doi.org/10.1101/2024.02.25.581928