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Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

ABSTRACT: Mammals differ more than 100-fold in maximum lifespan. Here, we conducted comparative transcriptomics on 26 species with diverse lifespans. We identified thousands of genes with expression levels negatively or positively correlated with a species' maximum lifespan (Neg- or Pos-MLS genes). Neg-MLS genes are primarily involved in energy metabolism and inflammation. Pos-MLS genes show enrichment in DNA repair, microtubule organization, and RNA transport. Expression of Neg- and Pos-MLS genes is modulated by interventions, including mTOR and PI3K inhibition. Regulatory networks analysis showed that Neg-MLS genes are under circadian regulation possibly to avoid persistent high expression, whereas Pos-MLS genes are targets of master pluripotency regulators OCT4 and NANOG and are upregulated during somatic cell reprogramming. Pos-MLS genes are highly expressed during embryogenesis but significantly downregulated after birth. This work provides targets for anti-aging interventions by defining pathways correlating with longevity across mammals and uncovering circadian and pluripotency networks as central regulators of longevity.

ORGANISM(S): Mesocricetus auratus Mus musculus Neotoma cinerea Myocastor coypus Peromyscus maniculatus Tamiasciurus hudsonicus Cuniculus paca Heterocephalus glaber Scalopus aquaticus Cricetulus barabensis Sciurus carolinensis Blarina brevicauda Hydrochoerus hydrochaeris Marmota monax Bramus lutescens Fukomys damarensis Chinchilla lanigera Octodon degus Rattus rattus Ondatra zibethicus Acomys russatus Cavia porcellus Tamias striatus Castor canadensis Condylura cristata

PROVIDER: GSE190756 | GEO | 2022/05/18

REPOSITORIES: GEO

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