Dublin Longevity Declaration

Consensus Recommendation to
Immediately Expand Research on
Extending Healthy Lifespans.

SUMMARY

An increase in healthy lifespans, through much better treatment of age-related diseases (dementia, heart disease, cancer, frailty, and many more), would deliver extraordinary benefits - including savings of trillions of dollars per year in healthcare costs.

Here, dozens of world-leading experts declare that such an advance is now potentially within reach, by targeting the underlying processes of aging, and that efforts to achieve it should be immediately and greatly expanded.

For millennia, the consensus of the general public has been that aging is inevitable.

For most of our history, even getting to old age was a significant accomplishment – and while centenarians have been around at least since the time of the Greeks, aging was never of major interest to medicine.

That has changed.  Longevity medicine has entered the mainstream.  First, evidence accumulated that lifestyle modifications prevent chronic diseases of aging and extend healthspan, the healthy and highly functional period of life.  More recently, longevity research has made great progress – aging has been found to be malleable and hundreds of interventional strategies have been identified that extend lifespan and healthspan in animal models.

Human clinical studies are underway, and already early results suggest that the biological age of an individual is modifiable.

· · ·

A concerted effort has been made in the longevity field to institutionalize the word “healthspan”.  Why healthspan (how long we stay healthy) and not its side-effect of lifespan (how long we live)?

The reasons are linked more to perception than reality.  Fundamental to this need to highlight healthspan is the idea that individuals get when they are asked if they want to live longer.  Many imagine their parents or grandparents at the end of their lives when they often have major health issues and low quality of life.  Then they conclude that they would not choose to live longer in that condition.

This is counter to longevity research findings, which show that it is possible to intervene in late middle life and extend both healthspan and lifespan simultaneously.  Emphasizing healthspan also reduces concerns of some individuals about whether it is ethical to live longer.

· · ·

A drawback of this exists, though: many current longevity interventions may extend healthspan more than lifespan.  Lifestyle interventions such as exercise probably fit this mold.  Many interventions that have dramatic health-extending effects in invertebrate models have more modest effects in mice, and there is a concern that they will be further reduced in humans.

In other words, the drugs and small molecules that we are excited about today may, despite their hefty development costs and lengthy approval processes, only extend average healthspan by five or ten years and may not extend maximum lifespan at all.

Make no mistake, this would still represent a revolution in medical practice!

A five-year extension in human healthspan, with equitable access for all people, would save trillions per year in healthcare costs, provide extra life quality across the entire population and ameliorate the demographic challenges that are happening in the first half of this century.

Most experts in the field now acknowledge that this is a likely outcome in the near future and one focus of longevity medicine is now on achieving it.  But far more is possible.

· · ·

Arguably, the avoidance of an emphasis on lifespan is a consequence of an overly pragmatic approach to two fundamental questions:

Why do humans age and what can we do about it?

These are surely two of the biggest questions in human biology.  Although we try our best to ignore it, the prospect of an inevitable decline in health leading to mortality shapes our thoughts and actions.  Despite the incredible advances in longevity research, these questions remain unanswered.

  • What biological processes bring about the aged state?
  • Can aging not just be significantly slowed, but more and more thoroughly reversed?
  • How would humans, and their societies, be different if we achieve these goals?

It will cost billions of dollars in research and significant time to answer such questions, but we assert that it would undoubtedly pay for itself many times over.  The case can (and will) be made that these questions should be answered because the knowledge gained will inevitably lead to major medical advances.

Another reason is the one that is not utility-driven, but rather the classic “knowledge for knowledge’s sake” argument.  Understanding ourselves and the organisms around us used to be reason alone to do research, and answering basic questions reliably yields utility in the future.  Penicillin comes to mind!  But the quest for knowledge, especially on ubiquitous topics such as aging, is worthy in its own right.

· · ·

Achieving much better control of aging would not mean immortality, of course.  Nevertheless, it would dramatically change the world we live in and how we live in it.  Life quality may expand, fear of loss of independence may diminish and, over time, the fabric of our world may radically improve.

What would it mean?

  • Imagine the energy of youth combined with the wisdom of experience.
  • Think about living long enough for space travel.
  • Imagine going back to school at 80 to study the latest in scientific breakthroughs, starting a new career, seeing your great-great-grandkids.

Yes, there will be unexpected outcomes and some might raise new challenges — but the same was true of past technological advances that few of us would give back.

How many of us want to go back in time now?  How many will want to in the future?

· · ·

Optimism about a better future drives us still, and one way to move forward is to answer the big questions in biology. The grand challenge of aging is foremost among these.

What cards need to be turned over to answer the longevity question?  What interventional strategies are likely to take us beyond modest healthspan effects, and toward radical change in the rate of biological aging? — beyond rough knowledge of the biology underlying aging, toward true understanding?

Biogerontological research is often reductionist in nature, drilling down to the pathways, proteins and genes that influence how we age.  This has been successful, but it is now evident that the processes that control aging represent an inter-linked network of interactions that eventually cause the aged phenotype to emerge at the whole-organism level.  A new systemic thinking is needed to solve the “why we age” question.  Strategies need to be employed to reconstruct the molecular alterations and pathways and integrate them into a unified model that explains aging.

Such a synthesis requires a multi-disciplinary approach combining methods and tools from molecular biology, complex systems theory, and the physical and engineering sciences.  It can be greatly facilitated by the growing availability of human biomedical data, such as Electronic Medical Records.  AI-driven modeling is making progress in this arena, leading to measures of biological age, new interventions and understanding of the relative contributions of different aspects of aging.

However, it is important to move beyond black-box modelling to obtain meaningful models of the aging process which can not only describe, but also explain that process in terms that are understandable and actionable.

· · ·

Most of the lifestyle or small-molecule interventions that are currently being tested target pathways affecting longevity.  These include those designed to improve metabolism, restore youthful immune function, maintain youthful body composition, eliminate deleterious cells or improve cellular stress responses.

But there are strategies on (and just over) the horizon that may have much bigger impact.  These need to be seriously interrogated and resources need to be devoted to these big questions.  There needs to be an acceptance and tolerance of significantly higher levels of failure in longevity research, knowing that big ideas are sometimes wrong and that the ones that are right will far outweigh the setbacks.

Below, we list some of the promising interventional ideas on the horizon and speculate on what is not yet visible.

These (and other) examples should be the basis for discussion by a taskforce designed to re-invigorate the concept of achieving control over our most inevitable biological outcome – age-related morbidity and mortality.

Some Emerging Strategies and Questions:

  • Combinatorial approaches – Can multiple systems be targeted simultaneously and will that yield synergistic outcomes?
  • Novel classes of small molecules – We have only explored a narrow subset of the small-molecule space for longevity outcomes.  Will larger-scale screens or even novel screening approaches result in enhanced lifespan extension?
  • Cellular reprogramming – Can we reprogram somatic cells in our tissues to a state to promote replacement of damaged cells and restoration of youthful tissue function?
  • Approaches based on species longevity – Can we utilize adaptations of long-lived species to achieve human longevity comparable to nature’s greatest successes, exceeding the modest changes delivered by existing interventions?
  • Gene and cell therapy – Long promised, both gene therapy and cell therapy have become feasible.  Can they be employed to target aging or age-related conditions?
  • Novel targets – for example, gene therapies derived from multi-omics studies.  Can they delay or reverse aging processes?
  • Emerging strategies to reverse age-related deterioration of the epigenome – There is good evidence that this deterioration reduces our control of endogenous parasites such as retrotransposons and retroviruses and increases age-related inflammation.  Can it be repaired?
  • Personalizing aging interventions – While general events are likely to drive aging, their relative impacts in each individual are likely to vary, therefore understanding how to optimize interventions to the individual will likely have higher yields.
  • Over the horizon – Often regarded as science fiction, strategies such as cryopreservation, brain mapping and ex vivo organ generation may ultimately be feasible.  We should keep open the possibility that dramatic lifespan extension may involve technologies that we haven’t fully imagined yet.

· · ·

Is radical lifespan extension foreseeable?  No one can answer that question with certainty.  But there are certainly enough tantalizing clues suggesting that aging is sufficiently malleable to warrant the allocation of very substantial resources.

Imagine a world where we control aging – possibly the biggest breakthrough yet in the ever-changing human condition.

SIGNATORIES

Brian KennedyDistinguished Professor of Biochemistry and Physiology, National University of Singapore
Aubrey de GreyPresident & Chief Science Officer, Longevity Escape Velocity (LEV) Foundation
Martin O'DeaVice Chair, Longevity Escape Velocity (LEV) Foundation
George ChurchRobert Winthrop Professor of Genetics, Harvard Medical School; Professor of Health Sciences and Technology, Harvard and MIT
David SinclairProfessor of Genetics, Harvard Medical School
James NelsonPresident, Gerontological Society of America; Professor of Physiology, Barshop Institute for Longevity and Aging Research
Eric VerdinProfessor, President and CEO, Buck Institute for Research on Aging
Ronald DePinhoBurkhart Distinguished University Chair in Cancer Research and Past President, University of Texas MD Anderson Cancer Center
Maria BlascoDirector, Spanish National Cancer Research Centre (CNIO)
Vadim GladyshevProfessor of Medicine, Harvard Medical School
Nir BarzilaiProfessor of Medicine and Genetics and Director of the Institute for Aging Research, Albert Einstein College of Medicine
Matt KaeberleinProfessor of Pathology, University of Washington in Seattle
Vera GorbunovaDoris Johns Cherry Professor of Biology, University of Rochester
Andrei SeluanovProfessor of Biology and Medicine, University of Rochester
Michael RoseDistinguished Professor of Biological Sciences, University of California, Irvine
Camillo RicordiProfessor of Surgery and Director of the Cell Transplant Center, University of Miami
Gerald SchattenProfessor of Obstetrics, Gynecology and Reproductive Sciences, Cell Biology, and Bioengineering, University of Pittsburgh
Andrea MaierOon Chiew Seng Professor in Medicine, Healthy Ageing and Dementia Research, National University of Singapore
Valter LongoEdna M. Jones Professor of Gerontology and Biological Sciences, University of Southern California
Björn SchumacherProfessor for Genome Stability in Aging and Disease, University of Cologne
Evelyne BischofProfessor of Medicine, Shanghai University of Medicine and Health Sciences
Jan VijgProfessor of Genetics and Professor of Ophthalmology & Visual Sciences, Albert Einstein College of Medicine
Yousin SuhProfessor of Reproductive Sciences (in Obstetrics and Gynecology) and of Genetics & Development, Columbia University
Thomas RandoProfessor of Neurology and Molecular, Cell & Developmental Biology, University of California, Los Angeles
Steven AustadDistinguished Professor of Biology, University of Alabama at Birmingham
Andrzej BartkeDistinguished Scholar and Professor of Internal Medicine and Physiology, Southern Illinois University
Mike WestFounder and CEO, AgeX Therapeutics
Bill AndrewsFounder and CEO, Sierra Sciences
Alex ZhavoronkovFounder and CEO, Insilico Medicine
Liz ParrishFounder and CEO, BioViva USA
Arlan RichardsonProfessor of Geriatric Medicine, University of Oklahoma Health Sciences Center
Marco QuartaCo-Founder and CEO, Rubedo Life Sciences
Rochelle BuffensteinResearch Professor, University of Illinois at Chicago
Jan GruberAssociate Professor of Biochemistry, Yale-NUS College
Peter FedichevCo-Founder and CEO, GERO
Morten Scheibye-KnudsenAssociate Professor, University of Copenhagen
Peter RabinovitchProfessor Emeritus, University of Washington
Holly Brown-BorgChester Fritz Distinguished Professor of Pharmacology, Physiology & Therapeutics, University of North Dakota
Luigi FontanaProfessor of Medicine and Nutrition and Leonard P Ullmann Chair in Translational Metabolic Health, University of Sydney
Andrei GudkovProfessor of Oncology, Roswell Park Comprehensive Cancer Center
Rozalyn AndersonProfessor of Medicine, University of Wisconsin
Randy StrongProfessor of Pharmacology, Barshop Institute for Longevity and Aging Research
Julie AndersenProfessor, Buck Institute for Research on Aging
Vincent MonnierProfessor of Pathology and Biochemistry, Case Western Reserve University
Ellen Heber-KatzProfessor, Lankenau Institute for Medical Research
Joanna BenszFounder and CEO, Longevity Center, Europe
Emma TeelingProfessor of Zoology, University College Dublin
Zoltán UngváriDonald W. Reynolds Chair of Aging Research, University of Oklahoma Health Sciences Center
John TowerProfessor of Biological Sciences and Gerontology, University of Southern California
Georg FuellenProfessor of Medical Bioinformatics, Institute for Biostatistics and Informatics in Medicine and Ageing Research
Barbara Shukitt-HaleUSDA-ARS Research Psychologist (Neuroscience and Aging), Tufts University
Alexey MoskalevDirector of the Institute of Biogerontology, Lobachevsky State University
Dudley LammingAssociate Professor of Medicine, University of Wisconsin-Madison
Patrizia d'AlessioFounder and CEO, AISA Therapeutics
Tina WoodsFounder and CEO, Collider Health
Danica ChenProfessor of Metabolic Biology, Nutritional Sciences & Toxicology, University of California, Berkeley
Christiaan LeeuwenburghProfessor of Aging and Geriatrics and of Anatomy and Cell Biology, University of Florida
Mikhail BlagosklonnyProfessor of Oncology, Roswell Park Comprehensive Cancer Center
Graham PawelecProfessor of Experimental Immunology, University of Tübingen
Claudia GravekampProfessor of Microbiology & Immunology, Albert Einstein College of Medicine
Janko NikolichProfessor of Immunobiology and Medicine, University of Arizona
Andrew SteelePresenter and Author, “Ageless: The New Science of Getting Older Without Getting Old”
João Pedro de MagalhãesProfessor of Molecular Biogerontology, University of Birmingham
Sebastian BrunemeierCo-Founder and General Partner, Healthspan Capital; CEO and Founder, ImmuneAGE Bio
Tilman GruneProfessor of Molecular Toxicology, University of Potsdam
Gregory BrewerProfessor of Systems Neuroengineering, University of California, Irvine
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We wholeheartedly encourage anyone who supports the message of the Dublin Longevity Declaration to add your signature, and to urge others to do the same.

We believe that demonstrating both expert consensus and broad public support for the extension of healthy lifespans will have the greatest impact, in swaying policymakers and institutions to acknowledge and align with the paradigm shift now taking root across medical science.

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FREQUENTLY ASKED QUESTIONS

What does the Declaration aim to achieve?

As the Declaration begins by noting: "For millennia, the consensus of the general public has been that aging is inevitable."  Due to that assumption, efforts to combat aging are widely seen as unworthy of serious recognition or support.

What few of the public realise is that a very different consensus has now emerged amongst experts on the topic.  The Declaration's principal signatories - who include most of the world's leaders in the biology of aging - have joined together to announce that success in such efforts could truly be achievable.

Their message urges all those who influence public and private opinion, policy, and funding, to acknowledge and act on that fact.

The extraordinary social and economic potential of longevity medicine has been recognised by authorities in those fields for many years.  The time has come for an equally extraordinary campaign to realise it: to free humanity from the blight of aging and its diseases.

What’s the evidence that “A five-year extension in human healthspan, with equitable access for all people, would save trillions per year in healthcare costs?
See the Nature Aging article “The economic value of targeting aging” by Andrew J. Scott, Martin Ellison, and David A. Sinclair - extract: “We show that a slowdown in aging that increases life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.  Ultimately, the more progress that is made in improving how we age, the greater the value of further improvements.”
What is the relationship between the Dublin Longevity Declaration and LEV Foundation/Dr. Aubrey de Grey?
Brian Kennedy and Aubrey de Grey are the scientific co-authors of the original text, with amendments also suggested by some of the initial signatories.  LEVF is publishing the Declaration on behalf of the signatories, handling the collection of additional signatures, and supporting media outreach.
Why is it the “Dublin” Longevity Declaration?
The ideas for the Declaration were discussed with speakers in the run-up to the Longevity Summit Dublin held in August 2023, where the forthcoming launch of the Declaration was also first announced.
If the field of longevity medicine has already entered the mainstream, as you state, what value does the Declaration add?
What’s at issue is the scale of the potential improvements in healthy human longevity, and the pace at which these improvements can be made.  The Declaration seeks to raise wider awareness of the scale of possible improvements, and to increase the pace at which these happen.  As the Declaration states, “Far more is possible"  than what would ensue from a modest continuation of existing trends.