CausAge (causality-aware clock)

CausAge is an epigenetic-age clock introduced by de Lima Camillo and colleagues (preprint 2022; Nature Aging 2024) that attempts to address a fundamental limitation of correlation-trained clocks: standard elastic-net or regression clocks select CpG sites associated with age without distinguishing whether the methylation change causes, results from, or merely co-varies with the ageing process. CausAge applies Mendelian-randomization-informed causal inference to identify CpGs whose methylation change is more likely upstream of biological ageing, and separately derives DamAge (damage-associated accelerated ageing) and AdaptAge (adaptive response) sub-clocks. The framework suggests that clock CpGs are heterogeneous in their causal role and that mortality-associated acceleration may be driven primarily by damage-linked sites rather than adaptive ones.