1 research outputs found
Smurfnessâbased twoâphase model of ageing helps deconvolve the ageing transcriptional signature
International audienceAgeing is characterised at the molecular level by six transcriptional âhallmarks of ageingâ, that are commonly described as progressively affected as time passes. By contrast, the âSmurfâ assay separates highâandâconstantâmortality risk individuals from healthy, zeroâmortality risk individuals, based on increased intestinal permeability. Performing whole body total RNA sequencing, we found that Smurfness distinguishes transcriptional changes associated with chronological age from those associated with biological age. We show that transcriptional heterogeneity increases with chronological age in nonâSmurf individuals preceding the other five hallmarks of ageing that are specifically associated with the Smurf state. Using this approach, we also devise targeted proâlongevity genetic interventions delaying entry in the Smurf state. We anticipate that increased attention to the evolutionary conserved Smurf phenotype will bring about significant advances in our understanding of the mechanisms of ageing