Peripheral Epigenetic Aging Predicts Survival Beyond Brain Aging-Related Biomarkers in Centenarians

GrimAge epigenetic aging in 247 Dutch centenarians is linked to mortality, with higher GrimAge acceleration predicting greater death risk (HR per SD = 1.41, 95% CI 1.22–1.63).

• Why it matters: Even after surviving to age 100, it remains unclear which aging-related signals still predict survival beyond cognition and brain/neurodegeneration biomarkers.
• What they did: Using PacBio long-read sequencing, the study compared five DNA methylation clocks with cognition, AD-related blood biomarkers, hematology, and neuropathology, then tested mortality associations with and without MMSE and leukocyte composition adjustment.
• The result: GrimAge predicted mortality independently of MMSE and leukocyte composition, and combining GrimAge with MMSE improved survival stratification (restricted mean survival difference 1.61 years vs 1.45 for GrimAge and 1.20 for MMSE alone).