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Aging clocks

DamAge / AdaptAge (causal damage clocks)

DEDamAge / AdaptAge (kausale Damage-Uhren)

DamAge and AdaptAge are 'causality-aware' epigenetic clocks. Kejun Ying and colleagues built them in the Gladyshev lab at Harvard / Brigham and Women's Hospital (Nature Aging, 2024). Do not confuse them with stress-induced 'damage clocks' like the Sinclair lab's ICE-based ones (Yang et al., Cell 2023). Those track induced epigenetic drift, not causal methylation. Standard DNA-methylation clocks (Horvath, Hannum, GrimAge) predict age well. But they cannot tell you one key thing: whether a given CpG change causes aging or just results from it. To get at cause, the authors ran epigenome-wide Mendelian randomization against longevity and disease GWAS. They found CpGs causally linked to harmful aging, and built DamAge from them. (Those are damaging methylation changes that speed biological age and track with death.) They also found CpGs causally linked to good outcomes, and built AdaptAge from those. (Those are protective changes that reflect the body compensating.) Both split the broader CausAge signal by causal direction. They respond to short-term interventions. And they make biological-age studies easier to interpret.

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Sources

  1. Ying K, Liu H, Tarkhov AE, et al.. (2024). Causality-enriched epigenetic age uncouples damage and adaptation. *Nature Aging*doi:10.1038/s43587-023-00557-0
  2. Horvath S. (2013). DNA methylation age of human tissues and cell types. *Genome Biology*doi:10.1186/gb-2013-14-10-r115
  3. Liu Z, Leung D, Thrush K, et al.. (2020). Underlying features of epigenetic aging clocks in vivo and in vitro. *Aging Cell*doi:10.1111/acel.13229