#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller

A roundtable discussion reveals the intricacies of defining and measuring healthspan versus lifespan—an often misunderstood distinction in aging research that has significant implications for society.

Healthspan vs. Lifespan: An Important and Often Misunderstood Distinction in Aging Research

Healthspan: Time Without Disability/Disease; Lifespan: Total Life Duration

The conversation reveals that "healthspan" refers to the period in which an individual is free from disability and disease, contrasted with "lifespan," which measures the total duration of life. Steven Austad notes that people are experiencing a growing gap between healthspan and lifespan, particularly in the United States, and more so among women than men. This trend underscores the need for a dual focus on delaying aging and extending healthspan simultaneously.

Healthspan and Lifespan Gap Growing In U.S

The discussion considers the possibility of improving healthspan without necessarily extending lifespan. Targeting the biology of aging could potentially delay the onset of chronic diseases that many Americans now live with for decades, as suggested by Matt Kaeberlein.

Measuring Biological vs. Chronological Age Is a Challenge

Biomarkers Reveal Insights Into Biological Age, but Determining a Single "Biological Age" Number Is Difficult and Misleading

Miller criticizes the concept of assigning a single "biological age" number, pointing out the complexity of various health issues and the unhelpful nature of reducing complex data into a single value. Attia and Austad echo this sentiment, arguing the difficulty of validating such measures in humans. The former also dismisses the idea of a single biological age number lacking utility and meaningfulness in clinical settings.

"Multiple Biomarker Aging Indicators May Surpass Single Biomarkers, but Validation in Humans Is Challenging"

Miller introduces the idea of aging rate indicators, such as a dozen variables that change with age across tissues like fat, blood, liver, brain, and muscle, which could be more informative tha ...

The podcast explores the burgeoning public fascination with longevity science, discussing substantial advances and the hype surrounding the promise of extended lifespans.

Advances In Modulating Aging Spark Interest in Longevity

Enthusiasm for longevity science has been ignited by landmark discoveries and growing belief in the potential to alter the aging process.

Lifespan-Extending Discoveries in Model Organisms Capture Public Imagination

Richard Miller talks about significant scientific breakthroughs that have demonstrated the potential for lifespan extension in model organisms such as mice. These findings, particularly concerning the efficacy of certain pills, have led to a natural curiosity about the prospect of achieving similar outcomes in humans.

Tech Entrepreneurs and Aging Baby Boomers Fuel Longevity Science Hype

Steven Austad expresses surprise at the burgeoning interest in longevity, especially as the field historically emphasized increasing health span over longevity to avoid the unwanted implications of prolonging frailty. This shift in focus aligns with the concerns of an aging baby boomer population and a new breed of tech entrepreneurs who believe that the aging process can be 'solved,' potentially leading to healthier and longer lives. Matt Kaeberlein underscores the impact influencers and public figures have had in garnering broader public attention toward the science of longevity, especially through the framework of the "hallmarks" of biological aging.

Public Interest Fuels Unproven "Anti-Aging" Products

Despite scientific advancements, the explosion of public interest has led to a proliferation of unproven anti-aging products.

Longevity Science Must Balance Enthusiasm and Rigor

Kaeberlein and Miller delve into the persistent popularity of substances like resveratrol, which, despite scient ...

Richard Miller, Matt Kaeberlein and Steven Austad explore the complex landscape of longevity research, discussing the significant challenges related to funding, prioritization, and the translation of animal research findings to humans.

Funding and Prioritization Challenges Hinder Aging Biology Research

The conversation around longevity research reveals deep-rooted issues within the funding infrastructure and research focus, particularly in relation to the National Institutes of Health (NIH).

Disease-Focused NIH Funding Fosters "Turf Wars" That Deter Integrative Aging Research

Richard Miller describes the defensive posture of specialized researchers, such as cardiologists and oncologists, who resist reallocating funds from their areas to aging research, which he likens to a "porcupine defense." These researchers maintain the urgency of their fields over aging research. Miller also shares his unsuccessful attempts to gain interest from cancer scientists in anti-aging drugs, which face resistance due to an entrenched focus on traditional cancer research avenues, rather than viewing aging as a potential key to understanding various diseases.

NIH Allocates Small Fraction of Budget To National Institute On Aging Despite Role in Major Diseases

Miller and Kaeberlein express frustration with the low levels of NIH funding allocated for aging research, a sentiment that Miller has upheld for over 30 years. They note that the NIH only allocates approximately half of one percent of its budget to the biology of aging despite the NIA receiving about 3% of the NIH's total budget. This indicates that funding for aging biology hasn't increased proportionally with overall NIH budget increases. The conversation suggests an acknowledgment of the importance of senescence research by the NIH, but implies skepticism in the current focus and hints at the necessity for more diversified approaches in aging research.

Animal-To-human Research Translation Hurdle

A significant portion of the conversation centers around the hurdles of translating animal longevity research to humans due to differences in physiology and lifespan.

Physiological and Lifespan Differences Hinder Result Extrapolation

Austad points out that substances found in human blood differ significantly from those in mice blood, emphasizing the challenge of extrapolating research results due to physiological differences. Similarly, Richard Miller acknowledges that most interventions effective in mice fail to show the same outcomes in human trials, which could be due to species differences or side effects that are tolerable in mice but not in humans.

Peter Attia discusses the limite ...

In a rich discussion filled with diverse opinions and expertise, Richard Miller, Matt Kaeberlein, Steven Austad, and Peter Attia examine the challenges associated with assessing aging interventions such as rapamycin and dietary modifications, as well as the potential and limitations of biomarkers for aging, particularly those associated with the epigenome.

Challenges In Assessing Geroprotective Interventions Like Rapamycin and Calorie Restriction in Humans

The discourse touches upon the complexities of translating animal study results to humans in the context of geroprotective interventions.

Animal Studies Show Interventions Can Extend Lifespan; Mechanisms May Differ In Humans

Miller and Kaeberlein delve into the subject of geroprotection in mice studies. While interventions like rapamycin have shown extension of lifespan in such animal models, Kaeberlein suggests that the same effects seen in mice and dogs with rapamycin could hopefully be seen in humans. However, they recognize the hurdles in directly translating these findings to human health benefits, with Miller expressing a preference for testing individual chemicals with known mechanisms over complex mixtures.

Lack of Reliable Biomarkers Complicates Evaluation of Biological Aging Interventions

The lack of reliable biomarkers for biological aging comes to the forefront as a significant obstacle. Richard Miller sees the idea of measuring biological age as outdated, while Matt Kaeberlein points out the imprecision and inaccuracy present in direct-to-consumer biological age kits.

Epigenome Changes Proposed As Causal Drivers of Aging, but Evidence Remains Correlational

As the conversation evolves, the participants explore the role of the epigenome in aging, considering both its correlation with aging processes and the challenges in establishing causality.

Epigenetic Clocks Show Promise, but Require Validation for Accurate Lifespan and Healthspan Prediction

Kaeberlein positions epigenetic clocks as a tool of promise for predicting lifespan and healthspan, yet he emphasizes the need for further validation. His experience with direct-to-consumer kits demonstrates varied results, which undermines their reliability as an accurate marker for agin ...

In a roundtable discussion, experts tackle the complex issue of funding and political challenges that impact the prioritization of foundational aging research over disease-specific research.

Disease-Specific Funding at Major Research Agencies Hinders Integrative Aging Research

Research in aging biology is often overshadowed by more disease-specific fields such as oncology, neurology, and cardiology. Steven Austad and Richard Miller suggest that there's significant resistance within these established fields to integrating aging biology research, viewing it as competition for limited resources. Despite aging being a major risk factor for many diseases, only a small fraction of research funding is dedicated to studying it. There is a need for increased advocacy to change this and to convince policymakers and the public of the benefits of aging research.

Oncology, Cardiology, and Neurology Researchers Resist Diverting Resources To Aging Biology, Viewing It As Competition

Richard Miller recounts his experience of facing immediate political pushback when suggesting that even a fraction of Alzheimer's funding should be redirected to study aging. He notes that fields like oncology and neurology might put up significant resistance to such reallocations. Miller also highlights that lobbyists heavily influence Congress, implying that the aging research field does not have enough lobbyists to compete with other disease-focused groups.

Advocacy Needed to Convince Policymakers and Public of Aging Research Benefits

Kaeberlein emphasizes the need to inform the public and policymakers that focusing on preventing diseases by targeting aging is more efficient than trying to cure them after they develop. To allocate more research budget toward aging, advocates must effectively communicate these benefits. The panel believes that progress will come but requires concerted effort to shift the biomedical research paradigm.

Private Sector and Alternative Funding Can Supplement Limited Public Research Funding

As public funding for foundational aging research faces challenges, the private sector could play a significant role in supplementing this lack of support.

Biotech and Pharmaceutical Firms Face Challenges in Geroprotective Development

Kaeberlein mentions the funding difficulties for testing various geroprotective interventions. However, Austad points out that private c ...