The Peter Attia Drive• Jul 21, 2025• 2:12:31Interview

357 ‒ A new era of longevity science: models of aging, rapamycin trials, biological clocks, & more

From The Peter Attia Drive

Brian Kennedy•Former CEO, Buck Institute

Executive Summary

The longevity research field has matured significantly, with a major inflection in investor and philanthropic interest around 2017-2018, moving from a niche academic pursuit to a more robustly funded area.
Rapamycin is considered the current 'gold standard' small molecule for targeting the aging process, primarily through its role in reducing mTOR signaling, which is linked to the core aging mechanism of chronic inflammation.
Systematic human clinical trials are underway in Singapore to test interventions like rapamycin and alpha-ketoglutarate (AKG), aiming to translate promising findings from animal models into tangible healthspan benefits for humans.
Measuring the efficacy of longevity interventions remains a major challenge, as current commercial epigenetic clocks are unreliable, highlighting the urgent need for validated biomarkers like the promising new clinical chemistry-based clock.

12 quotes

Concerns Raised

Current commercial epigenetic aging clocks are unreliable and show poor agreement with each other, hindering accurate measurement of intervention efficacy.
Combining different longevity interventions may lead to antagonistic effects where they cancel each other out, rather than providing additive or synergistic benefits.
The historical failure of high-profile programs, like GSK's resveratrol acquisition, can slow down investor interest and funding for the entire longevity field.
The Alzheimer's field has been significantly hindered by an overly narrow focus on amyloid plaques, serving as a cautionary tale for the aging field.

Opportunities Identified

Developing and validating new, more accurate biological aging clocks, such as one based on clinical chemistry from the NHANES dataset, which could revolutionize clinical trials.
Systematically testing promising geroprotectors like rapamycin, AKG, and SGLT2 inhibitors in well-designed human clinical trials to validate their effects on healthspan.
Leveraging the significant increase in philanthropic and investor interest since 2017-2018 to fund high-impact translational research.
Exploring novel delivery systems, such as sublingual NAD with a CD38 inhibitor, to overcome bioavailability issues with key compounds.

Key Themes

The Evolution of Longevity Research and Funding

The discussion traces the growth of the longevity field from the establishment of pioneering institutions like the Buck Institute to a significant surge in funding and interest around 2017. This shift was influenced by high-profile corporate ventures like Calico and setbacks like the GSK resveratrol program, which shaped investor sentiment over time.

This provides context for the current landscape of longevity science, explaining the transition from a purely academic field to a major area for biotech investment and philanthropic support.

Translational Science: From Model Organisms to Humans

The guest details a research pipeline in Singapore that systematically tests potential longevity interventions across a range of species, from yeast and worms to mice and ultimately humans. This approach is designed to increase the probability of success by validating interventions in diverse biological systems before committing to expensive and lengthy human trials.

This highlights a rigorous, structured approach to drug and supplement discovery in the aging space, moving beyond isolated animal studies to a more integrated and clinically relevant framework.

Key Molecular Pathways and Interventions

The conversation centers on the mTOR pathway and its connection to chronic inflammation as a core, targetable mechanism of aging. Specific interventions like rapamycin (mTOR inhibitor), alpha-ketoglutarate (AKG), and urolithin A are discussed as promising candidates currently being evaluated in both animal and human studies.

This identifies the most promising molecular targets and compounds in current longevity research, offering insight into the scientific rationale behind today's leading anti-aging strategies.

The Challenge of Measuring Biological Age

A critical challenge discussed is the inability to accurately measure the rate of aging. The episode highlights the poor reliability and agreement of current commercial epigenetic clocks, while also pointing toward the development of more robust biomarkers, such as a new clock based on standard clinical chemistry data.

Progress in the field is fundamentally limited by the quality of its measurement tools. Developing and validating accurate aging clocks is essential for proving the efficacy of any intervention in a reasonable timeframe.

A Systems-Level View of Aging

The guest argues against a simplistic strategy of targeting the 'Hallmarks of Aging' one by one, emphasizing that these processes are deeply interconnected. This complexity is further illustrated by mouse studies showing that combining different longevity interventions often leads to them canceling each other out rather than producing additive benefits.

This underscores the need for a more holistic understanding of aging biology, cautioning against overly simplistic intervention strategies and highlighting the challenges in developing effective combination therapies.

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Topics

Longevity Aging Research Healthspan mTOR Pathway Rapamycin Chronic Inflammation Biological Clocks Epigenetic Clocks Translational Science Animal Models Buck Institute Alpha-Ketoglutarate (AKG)Urolithin A NAD Precursors Clinical Trials Biotech Investing Geroprotectors Singapore

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