Comparative Liver Transcriptomics Identifies a Leverage-Sensitive Chromatin-Maintenance Expression Correlate of Mammalian Longevity

Maximum lifespan varies widely among mammals and is strongly correlated with adult body mass, but molecular correlates of longevity beyond body size remain incompletely understood. I tested whether liver expression of a predefined 16-gene chromatin-maintenance module was associated with mammalian maximum longevity after accounting for adult mass and phylogeny. Across 936 mammal species, adult mass was positively associated with maximum longevity in phylogenetic generalized least-squares (PGLS) analysis (β=0.126, P<0.001; λ=0.974). In a matched set of 19 species with liver RNA-seq data, chromatin-module expression showed a negative, marginal association with longevity after adjustment for mass and phylogenetic covariance (β=−0.137, SE = 0.069, P=0.067). Adding the module modestly improved model fit relative to mass alone (ΔAIC = 1.81). However, the association was highly sensitive to Sciurus carolinensis; excluding this species reduced the module effect to near zero (β=−0.0096, P=0.953). Thus, liver chromatin-maintenance expression may contain longevity-related information not captured by body mass, but the present evidence is preliminary and leverage-sensitive. Larger comparative datasets and direct measures of chromatin state are needed to evaluate this hypothesis.