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


ABSTRACT: 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.

SUBMITTER: Enriquez-Hesles E 

PROVIDER: S-EPMC7949035 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature

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

Enriquez-Hesles Elisa E   Smith Daniel L DL   Maqani Nazif N   Wierman Margaret B MB   Sutcliffe Matthew D MD   Fine Ryan D RD   Kalita Agata A   Santos Sean M SM   Muehlbauer Michael J MJ   Bain James R JR   Janes Kevin A KA   Hartman John L JL   Hirschey Matthew D MD   Smith Jeffrey S JS  

The Journal of biological chemistry 20201202


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 nonrest  ...[more]

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