Paper behind paywall
https://www.nature.com/articles/s43587-025-00969-0
Read only access may be here:
https://t.co/FYLcInTkFQ
AI summary:
Here’s a crisp summary of Sierra’s Nature Aging correspondence, “Are we getting closer to understanding why we age?”:
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Framing the field. Aging theories cluster into two camps—damage accumulation vs programmed aging. The 2013 Hallmarks of Aging and geroscience framework organized the field and helped move it toward clinical testing, aided by epigenetic clocks and newer pace-of-aging biomarkers.
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Core claim. While macromolecular damage (mutations, telomere loss, protein/lipid damage) rises with age, its pattern is not linear. Examples such as brain amyloid show little accumulation before ~40, then acceleration later. This suggests aging isn’t just passive damage buildup; rather, there’s an age-dependent failure of protective systems (the hallmarks), producing a system-level loss of “molecular resilience”—cells’ capacity to cope with diverse insults.
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Why resilience fails. Thermodynamics alone can’t explain the late-life acceleration or species differences. Evolutionary tuning does: species invest in repair/resilience only to the extent favored by their ecological niche and reproductive timing. Long-lived species (e.g., naked mole rat, whales, elephants) possess more robust defenses because longevity benefits reproduction in their niches. In humans, declining female reproductive fitness around 40–50 implies resilience built to last roughly to 60–70, after which it degrades.
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Implications.
- Prioritize molecular resilience as a unifying target above individual hallmarks and develop predictive measures of resilience and future health.
- Expand beyond standard lab models to comparative species that are “successful agers” for their niche, to learn diverse resilience strategies.
- Continue translating geroscience into human trials while refining biomarkers of aging trajectories, not just chronological age.
Bottom line: Aging reflects an evolutionarily tuned decline in molecular resilience across interconnected maintenance systems, leading to accelerated damage later in life. Advancing the field now hinges on measuring, comparing, and therapeutically bolstering resilience.