Attached is Part I of a two-part report exploring the biology of aging and the quest to extend human longevity.
Today’s installment provides an historical overview of aging research—its milestones, its thinkers, and the key theories.
Part II, coming soon, will examine the state of translational science today and outline where we think the aging field is heading.
It would be fair to say that most biotech investors avoid aging investments today with the view that the field is not translationally ready.
Almost universally, biotech investors prefer to stick to fields that they know well like oncology therapies, obesity drugs and the like.
At best, mainstream biotech investors view aging science as immature. At worst, they view the area as hopeless. This has been the lesson of past failures at companies like Hollis-Eden and Sirtris.
Further, investors will tell you that clinical trials for aging drugs are intractable because we live too long.
Oh and, by the way, there is no regulatory pathway for aging drugs. Dying is not a disease, and the FDA only approves drug for diseases.
Not being one to hold back the punchline, our core argument in our upcoming “Part II” report will be that this pessimistic view is ill-founded.
We will argue that the science of aging is not only translationally ready—but that it’s ripe for investment.
As will become clear from reading today’s report, aging research is specific about the core causes of limited human longevity.
The paths forward for interventions are clear enough.
Aging biology is maturing quickly, with well-defined mechanisms, testable hypotheses, and even regulatory precedents.
Further, there are multiple good ways to test aging theories in affordable trials that are less than five years in length.
And consider the FDA’s green light for the TAME trial, which studies metformin’s ability to delay age-related disease and mortality. The notion somehow that the FDA is not prepared to approve drugs that delay mortality is false.
We believe the next decade will see massive advances in aging science, with attendant opportunities for investors who take aging science seriously to prosper from well-informed bets.
Hence our work on progress in aging.
Why Start with History?
Today’s report is a foundational survey of aging research from antiquity to the present.
We trace over 200 influential publications—from a 1700 BC Egyptian medical text to papers published just this month.
Understanding the history will help provide:
- Context for evaluating current scientific developments;
- Appreciation for how deeply aging research is embedded in the long arc of the Scientific Revolution;
- Insight into today’s leading biological theories; and
- Perspective on the nature of scientific innovation—and why this moment matters.
We apologize ahead of time.
Our report is not brief and delves into substantial historical detail.
If you’re not drawn to this level of detail, we suggest reading up to page 25, then skipping to page 160, where the modern scientific narrative begins in earnest (circa 1975).
That narrative goes into detail about key developments in fields like oxidative stress theories of aging, integrated stress response theories, the role of DNA damage repair and other topics such as autophagy, cellular senescence, senolytic therapies, and cellular reprogramming. We have tried to make it easy to navigate your way through this with “box and arrow” maps that show the intellectual progression of recent research.
Humanity’s Timeless Fascination with Longevity
For over 5,000 years, humans have sought to overcome old age.
The desire to live longer, healthier lives is one of our oldest ambitions.
As early as the 11th century, the authors of the Regimen Sanitatis Salernitanum asked, “Oh that there were a medicine curing age…”
This report documents that pursuit: a historical journey through theories, discoveries, and the ever-evolving understanding of why we age and how we might intervene.
Some of the earliest insights remain strikingly relevant.
Alfred Russel Wallace, Darwin’s collaborator, argued in 1865 that aging serves an evolutionary purpose—useful after reproduction but ultimately a mechanism of biological turnover.
Today, aging research is accelerating at an astonishing pace.
If current publication trends continue, more scientific work will be done on aging in this decade alone than in the prior 5,000 years of human history combined.
We are at a major inflection point in human history.
The causes of aging at both cellular and organismal levels are increasingly well understood.
Interventions are being developed. And the science is becoming mainstream.
The Stakes Are Rising
The rigor and quality of today’s aging science has vastly improved compared to fifty—or even five—years ago. For instance, Calico Labs’s 2024 Nature paper revealed how the effects of calorie restriction on aging in mice vary dramatically by genotype—a finding with real translational potential.
At the same time, global dynamics are shifting.
While U.S. policymakers are making noises about reducing NIH funding, China is ramping up spend on the life sciences.
In this report, we highlight two state-funded Chinese labs making breakthroughs in cell rejuvenation therapeutics—potentially challenging leading U.S. players like Altos Labs.
The implications could be enormous.
Leadership in aging therapeutics could have profound economic and societal consequences for a nation that has a strong or blocking IP position in novel therapies.
It’s Easy to Miss the Big Picture
We live in a moment in history where the typical busy public biotech investor is focused on “inflection points” that might unfold in the next two or three months.
And we are all bathed in unending to-the-minute news events flashed at us from our phones. It is easy to lose sight of the fact this barrage of data and news flow might induce a myopia of sorts – one that masks the fact that research underway in the current decade has the promise to change the future of our species.
Specifically, science is making major progress in beating back the inevitability of death.
But the timescale is different. We’re not talking about instant news flow here. It’s years and decades – rather than days and weeks.
The Study of Aging is the Study of Us
Aging research is about more than just biology—it relates to religion, to myth, and to culture.
To study aging is to study ourselves.
As Joseph Campbell noted, myths surrounding death and aging have shaped human consciousness for millennia. From Gilgamesh’s futile quest for immortality to Hollywood’s modern echoes in The Age of Adaline, we’ve long wrestled with the implications of living forever.
These stories often warn us: immortality comes at a cost.
Myth, religion, and philosophy all encourage us to embrace our mortality.
Thinkers from Freud and Malinowski to Camus and Durkheim have examined how human culture helps us accept the inevitability of death.
But what if we’re approaching a world where longer, even indefinite lifespans, are possible? Might our stories evolve? Might our myths adapt?
I believe they could.
Biotech: A Civilizational Force
Biotechnology, the application of scientific knowledge to improve health, is one of the most powerful engines of societal change. Nowhere is this truer than in the field of aging.
The implications of breakthroughs in autophagy, DNA repair, and cellular reprogramming go far beyond traditional clinical trials. They touch every aspect of life: work, relationships, religion, law, and economics. Our legal system, inheritance structures, and our private property system, the very basis of capitalism – is built around the reality of finite life.
Homo sapiens is the only species known to be both aware of its mortality and to be undertaking organized efforts to delay mortality through research into its underlying causes.
Looking Backward to See Forward
Perhaps not surprisingly, many of the ideas underlying today’s aging research were anticipated long ago. Key researchers who helped to see what was to come include Charles Minot late in the 19th century, Robert Boyle in the 17th century and Leonard Hayflick in the 20th. For example, current progress in cell senescence was foreshadowed more than 200 years ago by Xavier Bichat and the amazing work today on cell reprogramming was foreshadowed 60 years ago by John Gurdon.
Of course, writing about respiration and aging in the 1670s, Boyle was neither aware of the existence of cells nor of mitochondria. He had no access to modern tools with which to conduct his investigations.
But as discussed in this survey, his experiments, intuition and insights made at the dawn of the Enlightenment are surprisingly relevant today.
New research tools in areas like mass spectrometry, binding assays, single cell analysis, flow cytometry, AI, Cryo-EM, transcriptomics, sequencing and the like have made it possible to carry out far more detailed and directed investigations than ever before.
Powered by new research tools, the field of aging research has gone from a niche area populated by iconoclasts and curious generalists to one that is in the scientific mainstream.
Importantly, real progress is being made. We hope that our survey of the history’s top texts on aging will give you a sense of the advancements underway in addressing humanity’s limited life span. This progress, of course, has not been easy given the underlying complexity of aging itself. To quote Venki Ramakrishnan, the 2009 Nobel Prize winner in Chemistry:
“…extending human life span – the longest we can expect to live in the best of circumstances – is a much tougher problem. Is our life span fixed, or could we slow down or even abolish aging as we learn more about our own biology?”
We thank you for taking the time to peruse and consider the material herein.
I hope that you can share some of the same pleasure that I have gained from contemplating our species’ efforts to understand and examine its limited life span. We are poised to make transformative breakthroughs in aging research.
The convergence of advances in genomics, artificial intelligence, and regenerative medicine holds the promise of unprecedented progress in extending human lifespan.
The history of aging research chronicled here is a testament to humanity’s enduring curiosity and ingenuity.
Best,
Tim Opler
Managing Director
Stifel Investment Banking
Direct Phone: +1 212-257-5802
oplert@stifel.com
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