A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.

Journal Article (Journal Article)

Caloric restriction (CR) improves health span and life span of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging-associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological life span (CLS). We found that conditioned media collected from stationary-phase CR cultures extended CLS when supplemented into nonrestricted (NR) cultures, suggesting a potential cell-nonautonomous mechanism of CR-induced life span regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in life span regulation.

Full Text

Duke Authors

Cited Authors

  • Enriquez-Hesles, E; Smith, DL; Maqani, N; Wierman, MB; Sutcliffe, MD; Fine, RD; Kalita, A; Santos, SM; Muehlbauer, MJ; Bain, JR; Janes, KA; Hartman, JL; Hirschey, MD; Smith, JS

Published Date

  • 2021

Published In

Volume / Issue

  • 296 /

Start / End Page

  • 100125 -

PubMed ID

  • 33243834

Pubmed Central ID

  • PMC7949035

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.RA120.015402


  • eng

Conference Location

  • United States