The study followed 247 Dutch centenarians, recruited for reported cognitive health, to test epigenetic ageing as a survival predictor. Five DNA methylation clocks from PacBio long-read sequencing were compared with MMSE, Alzheimer's-related blood biomarkers, blood cell measures and neuropathology. Only GrimAge was associated with both chronological age and mortality. Each standard deviation of GrimAge acceleration gave a mortality HR of 1.41 (95% CI 1.22-1.63), independent of MMSE. GrimAge plus MMSE gave a 1.61-year restricted mean survival gap between extreme quintiles, versus 1.45 (GrimAge) and 1.20 (MMSE). Plasma neurofilament light (NfL) also predicted mortality, but few temporally matched measurements limited tests of its independent effect on survival.
Why it is interesting: Mortality signals from blood epigenetic ageing persist even after survival to 100. GrimAge correlated strongly with haematological markers consistent with myeloid shift, yet these did not fully explain its survival link.
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