Study Identifies Shared Transcriptomic Patterns of Ageing Across Four Mammal Species

A new analysis integrated transcriptomic data from more than 11,000 samples across more than 25 tissues in four mammal species. The work produced biomarkers for chronological age and expected mortality that also predicted effects of lifespan-altering interventions.

Ageing-related gene expression changes were consistent across species and cell types. Two genes, CDKN1A and LGALS3, showed protein-level associations with mortality and multimorbidity in UK Biobank participants. Mortality-linked expression patterns appeared in multiple experimental damage models, including inflammation, replicative senescence, metabolic inhibition and gamma-irradiation.

These patterns were reduced or reversed by cell immortalization, cellular reprogramming, heterochronic parabiosis and early embryogenesis.

Network analysis identified modules covering inflammation, interferon signalling, mitochondrial function, chromatin modification and extracellular matrix organization. Module-specific clocks showed that chronic diseases mainly accelerated inflammatory-module ageing, while caloric restriction and Klotho deficiency affected mitochondrial and metabolic modules.

Transcriptomic and DNA methylation clocks displayed correlated age acceleration in human blood, strongest for the chromatin-associated module. The study supplies a framework for measuring and targeting ageing in specific cellular subsystems across tissues and species.