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January 27, 2025 • 2hr 41min
#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller
The Peter Attia Drive
This special roundtable episode featured three renowned experts in longevity science:
Steven Austad - Expert in aging biology and author of groundbreaking research on extending healthspan
Richard Miller - Pioneer of the Interventions Testing Program (ITP) studying anti-aging interventions
Matt Kaeberlein - Expert in genetics, aging and translational research, known for the Dog Aging Project
#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller
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Key Takeaways
- The field of longevity science has seen a dramatic surge in public interest, though experts debate whether this represents a "bubble" or sustainable growth
- There is strong disagreement about whether the "hallmarks of aging" framework has helped or hindered progress in the field
- Only about 0.5% of NIH research funding goes to studying biological aging, despite it being the greatest risk factor for most major diseases
- Current "biological age" tests, particularly direct-to-consumer epigenetic tests, lack sufficient validation and standardization
- Experts remain skeptical about senolytics and question whether cellular senescence represents a unified phenomenon
- Rapamycin shows consistent life-extending effects in mice but optimal dosing in humans remains unclear
- Evidence for metformin as a geroprotective agent in non-diabetics is limited
- The field needs both basic research into mechanisms and clinical trials of potential interventions
Introduction
This special roundtable episode featured three renowned experts in longevity science:
- Steven Austad - Expert in aging biology and author of groundbreaking research on extending healthspan
- Richard Miller - Pioneer of the Interventions Testing Program (ITP) studying anti-aging interventions
- Matt Kaeberlein - Expert in genetics, aging and translational research, known for the Dog Aging Project
Topics Discussed
The Rise of Public Interest in Longevity (3:45)
The panel discussed the recent dramatic increase in public interest in longevity science. Steve Austad noted this was surprising given the field's historical focus on healthspan rather than longevity.
- Key factors driving interest include:
- Tech entrepreneurs viewing aging as a solvable problem
- Maturation of the scientific evidence showing aging can be modified
- Growing public awareness of biological aging concepts
- "For a long time we tried to move away from [the term] longevity because we were worried people were thinking of longevity as 'we're going to keep frail, feeble old people alive longer'" - Steve Austad
Healthspan vs Lifespan Debate (12:30)
The experts engaged in a spirited debate about the relationship between healthspan and lifespan.
- Key points of discussion:
- The gap between healthspan and lifespan is increasing in the US, particularly among women
- Interventions that extend lifespan in model organisms typically also improve health
- The term "healthspan" lacks clear definition but remains conceptually useful
- "The notion that you get one or the other, that you have to make a choice...that's ridiculous and controverted by all the available evidence" - Richard Miller
Funding Challenges and Research Priorities (21:30)
The panel highlighted major challenges in securing adequate funding for aging research.
- Current funding situation:
- Only ~0.5% of NIH budget goes to biology of aging research
- Disease-specific institutes resist shifting funds to aging research
- Private sector funding is increasing but focuses on different priorities
- "Nine of the top 10 causes of death have biological aging as their greatest risk factor...yet half of 1% of the research budget goes to study that risk factor" - Matt Kaeberlein
Biological vs Chronological Age (35:00)
The experts discussed the concept of biological age and current methods to measure it.
- Key points on biological age measurement:
- Direct-to-consumer epigenetic tests show poor reproducibility
- Multiple tissue-specific aging rates may be more relevant than a single number
- Need for better validation of aging biomarkers
- "I don't believe there is one thing as biological age. I think there is potentially an age of your heart, an age of your liver, an age of your lungs, an age of your brain" - Steve Austad
The Hallmarks of Aging Framework (49:30)
There was significant debate about the value and limitations of the "hallmarks of aging" framework.
- Perspectives on the framework:
- Helped communicate aging biology to broader audience
- May have prematurely narrowed research focus
- Lacks clear evidence for relative importance of different hallmarks
- "It has been extremely detrimental to the field...it just caused the field to narrow prematurely" - Matt Kaeberlein
Epigenetic Changes in Aging (56:45)
The panel explored the role of epigenetic changes in aging and challenges in establishing causality.
- Key discussion points:
- Epigenetic changes clearly occur with age
- Causality remains difficult to prove
- Need for tissue-specific understanding
- "The concept of epigenetic change encompasses thousands of changes in hundreds of cell types under hundreds of influences" - Richard Miller
Translational Challenges (1:03:45)
The experts discussed challenges in translating findings from animal models to humans.
- Major challenges include:
- Longer timeframes needed for human studies
- Difficulty measuring outcomes
- Regulatory hurdles
- Cost of clinical trials
Cellular Senescence and Senolytics (1:46:15)
There was significant debate about cellular senescence and senolytic interventions.
- Key points of contention:
- Whether senescence represents a unified phenomenon
- Reproducibility of senolytic studies
- Clinical potential of senolytics
- "The notion that aging is due to senescent cell accumulation is bad for two reasons - it's a grotesque oversimplification and the evidence is awful" - Richard Miller
Metformin and Rapamycin (2:02:30)
The panel discussed two leading candidate geroprotective drugs.
- Metformin:
- Evidence in non-diabetics is limited
- TAME trial finally beginning enrollment
- Mechanism remains unclear
- Rapamycin:
- Consistent effects in mice
- Optimal dosing in humans unclear
- Complex mechanisms involving mTOR pathways
Future Directions (2:29:45)
The experts concluded by discussing future priorities for the field.
- Key priorities identified:
- Increased funding for basic aging research
- Better biomarkers and clinical trial endpoints
- More rigorous testing of interventions
- Greater collaboration across disciplines
Conclusion
This wide-ranging discussion highlighted both the progress and challenges in longevity science. While there is growing evidence that aging can be modified, major obstacles remain in translating findings to humans. The field needs both increased funding and more rigorous science to advance. The experts emphasized the importance of maintaining scientific skepticism while pursuing promising interventions.