Transcriptomic hallmarks of mammalian ageing and mortality identified through multi-species meta-analysis (nature.com)

• Multi-species transcriptomic clocks accurately predict chronological age and expected mortality across 4 mammals and 25+ tissues.
• Conserved ageing hallmarks include upregulation of inflammatory and p53 signaling, downregulation of mitochondrial translation and ECM components.
• Module-specific clocks enable pathway-level quantification of ageing and intervention effects, linking chronic diseases to accelerated inflammatory ageing.

"Integration of over 11,000 transcriptomes from 25 tissues across mouse, rat, macaque, and human reveals conserved transcriptomic signatures of ageing and mortality. Elastic net models produce accurate multi-tissue clocks for chronological age and expected mortality, identifying genes like CDKN1A and LGALS3 whose protein levels associate with mortality in UK Biobank. Network analysis uncovers modular architecture including inflammation, interferon, mitochondrial, chromatin, and ECM modules. Module-specific clocks show pathway-specific intervention effects, e.g., chronic diseases accelerate inflammatory module ageing, while caloric restriction targets mitochondrial modules. Transcriptomic and DNA methylation clocks correlate in human blood."