Author: J Yuyang Lu1, Matthew Simon1, Yang Zhao1, Julia Ablaeva1, Nancy Corson1, Yongwook Choi2, KayLene Y H Yamada3, Nicholas J Schork2, Wendy R Hood3, Geoffrey E Hill3, Richard A Miller4, Andrei Seluanov5, Vera Gorbunova6
Affiliation: <sup>1</sup> Department of Biology, University of Rochester, Rochester, NY 14627, USA.
<sup>2</sup> Quantitative Medicine and Systems Biology Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
<sup>3</sup> Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA.
<sup>4</sup> Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA.
<sup>5</sup> Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: andrei.seluanov@rochester.edu.
<sup>6</sup> Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: vera.gorbunova@rochester.edu.
Conference/Journal: Cell Metab
Date published: 2022 May 10
Other:
Special Notes: doi: 10.1016/j.cmet.2022.04.011. , Word Count: 167
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.
Keywords: aging; circadian clock; comparative transcriptomics; epigenetic reprogramming; functional genomics; longevity; pluripotency.
PMID: 35580607 DOI: 10.1016/j.cmet.2022.04.011