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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.

SUBMITTER: Lu JY 

PROVIDER: S-EPMC9364679 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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

Lu J Yuyang JY   Simon Matthew M   Zhao Yang Y   Ablaeva Julia J   Corson Nancy N   Choi Yongwook Y   Yamada KayLene Y H KYH   Schork Nicholas J NJ   Hood Wendy R WR   Hill Geoffrey E GE   Miller Richard A RA   Seluanov Andrei A   Gorbunova Vera V  

Cell metabolism 20220516 6


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 modu  ...[more]

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