25. Why do epigenetic clocks generalize so well?

Epigenetic clocks generalize because mammalian development writes a constrained epigenomic architecture, and aging perturbs that architecture in partially conserved ways. If the same classes of regulatory regions drift with time across tissues, species, and contexts, models trained in one setting can transfer. This does not imply a single universal cause; it implies that long-term maintenance has stereotyped failure modes. Additionally, the assays used are standardized (same CpG sites profiled), facilitating comparisons.