Amazing stuff!
"... A multinational team of researchers have now given us a powerful molecular clock that, with the help of biological markers, can predict age as well as the risk of death in mammals. ...
They discovered that certain genes serve as universal markers of aging, and that these genes behave almost identically across mammals as they get older, regardless of species. By analyzing gene expression of these markers across more than 11,000 samples from mice, rats, macaques, and humans, researchers developed a universal aging clock. ..."
"... The study also separated gene expression changes associated with aging and mortality into modules that represent different biological processes, such as inflammation, energy production, and extracellular matrix organization. The authors developed individual transcriptomic clocks for each module and showed that different diseases and medical or lifestyle interventions may affect biological age through distinct primary processes. ..."
From the abstract:
"Ageing and interventions modulate health and mortality, yet the underlying molecular mechanisms of this modulation remain unclear.
Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age and expected mortality, predicting lifespan-modulating interventions, time to death, chronic diseases and rejuvenation.
Ageing-related changes were conserved across species and cell types, revealing universal transcriptomic signatures of mammalian ageing and mortality, including CDKN1A and LGALS3, whose protein levels were also associated with mortality and multimorbidity in UK Biobank.
Mortality-associated features were recapitulated across in vivo and in vitro damage-accumulation models, including inflammation, replicative senescence, metabolic inhibition and γ-irradiation, and were attenuated or reversed by cell immortalization, reprogramming, heterochronic parabiosis and early embryogenesis.
Network analysis uncovered a modular architecture of ageing- and mortality-associated hallmarks, encompassing inflammation, interferon signalling, mitochondrial function, chromatin modification and extracellular matrix organization.
To quantify ageing of individual cellular components, we developed module-specific clocks, which revealed pathway-specific effects of interventions: chronic diseases primarily accelerated inflammatory-module ageing, whereas caloric restriction and Klotho (also known as Kl) deficiency targeted mitochondrial and metabolic modules.
Transcriptomic and DNA methylation clocks showed correlated age acceleration in human blood, which was strongest for the chromatin-associated module clock, highlighting mechanistic links between molecular ageing modalities. This study reveals conserved signatures and a modular architecture of mortality regulation, providing a framework for quantifying and targeting ageing of cellular subsystems across species and tissues."
Gene Expression ‘Clocks’ Reveal Shared Molecular Signatures of Aging and Mortality Across Mammals (original news release) "Mass General Brigham researchers identify conserved gene expression signatures linked to biological aging and risk of disease and mortality, offering a new framework for quantifying aging and evaluating interventions that modulate healthspan and lifespan"
Gene-expression patterns can be used to estimate mortality risk and chronological age (no public access) "Massive analyses of RNA transcripts from rodents, monkeys and humans reveal hallmarks of ageing that could expedite the development of anti-ageing interventions."
Fig. 1: Rodent multi-tissue transcriptomic clocks capture molecular changes associated with ageing and mortality.
Fig. 2: Transcriptomic biomarkers of ageing and mortality are conserved across mammalian species and cell types.
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