In a recent episode of The Drive podcast, Peter Attia invited aging scientist Dr. Brian Kennedy to explore breakthroughs in longevity research and practical methods that could extend our healthy years.

Two Models of Aging: Understanding Resilience

Dr. Kennedy introduces two complementary models to understand the aging process:

• Linear model — a steady buildup of biological damage.
• Oscillatory model — short-term fluctuations in physiological resilience.

Together, these models illustrate how aging is not only about the accumulation of decline, but also the fading ability to bounce back, making recovery from small challenges increasingly difficult. Most current interventions appear to influence only these oscillations—not the overall downward trajectory of aging.

The Quest for Better Aging Clocks

Biological clocks are critical tools that estimate someone’s “biological age” using biomarkers such as:

• DNA methylation
• Gene expression
• Proteomics
• Immune profiles

While methylation-based clocks get most of the attention, alternative approaches—including proteomic, metabolomic, and even facial-feature-based clocks—are showing promising accuracy. Many remain experimental, but are already proving useful in early-stage clinical trials where traditional markers of aging fall short.

Rapamycin: What Early Human Trials Reveal

Rapamycin, originally used as an immunosuppressant, has long shown anti-aging potential in animal studies. In an ongoing human trial in Singapore, adults aged 40–60 receive a low dose (5 mg once a week) over six months. Researchers are tracking:

• Inflammation markers
• Aging clocks
• Arterial stiffness
• Cognitive function
• Muscle strength

This study isn’t treating disease—it’s testing whether rapamycin can bolster resilience in otherwise healthy individuals, highlighting a shift toward preventative longevity strategies.

Natural Compounds on the Horizon: AKG, Urolithin A, Spermidine

Kennedy also touches on promising natural molecules:

• Alpha-ketoglutarate (AKG): A key metabolite in cellular energy cycles. Mouse studies show it extends lifespan and reduces frailty. A time-release AKG formulation is presently in human trials, exploring its effects on methylation clocks, inflammation, and physical function.
• Urolithin A and Spermidine: Though discussed as candidates for future research, the article doesn’t detail current human trial outcomes.

In Summary

Dr. Attia and Dr. Kennedy unpack how aging might be conceptualized not just as inevitable decline, but as diminishing resilience. They’re tracking a range of interventions—from biological aging clocks to rapamycin and promising natural compounds—with the goal of enhancing healthspan, not merely treating disease.