Smurfness-based two-phase model of ageing helps deconvolve the ageing transcriptional signature

Flaminia Zane, Hayet Bouzid, Sofia Sosa Marmol, Mira Brazane, Savandara Besse, Julia Lisa Molina, Céline Cansell, Fanny Aprahamian, Sylvère Durand, Jessica Ayache, Christophe Antoniewski, Nicolas Todd, Clément Carré, Michael Rera

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    4 Citations (Scopus)

    Résumé

    Ageing is characterised at the molecular level by six transcriptional ‘hallmarks of ageing’, that are commonly described as progressively affected as time passes. By contrast, the ‘Smurf’ assay separates high-and-constant-mortality risk individuals from healthy, zero-mortality 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 non-Smurf individuals preceding the other five hallmarks of ageing that are specifically associated with the Smurf state. Using this approach, we also devise targeted pro-longevity 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.

    langue originaleAnglais
    Numéro d'articlee13946
    journalAging Cell
    Volume22
    Numéro de publication11
    Les DOIs
    étatPublié - 1 nov. 2023

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