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

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2021-01, Vol.296, p.100125-100125, Article 100125
Main Authors: Enriquez-Hesles, Elisa, Smith, Daniel L., Maqani, Nazif, Wierman, Margaret B., Sutcliffe, Matthew D., Fine, Ryan D., Kalita, Agata, Santos, Sean M., Muehlbauer, Michael J., Bain, James R., Janes, Kevin A., Hartman, John L., Hirschey, Matthew D., Smith, Jeffrey S.
Format: Article
Language:English
Subjects:
aging
amino acids
Caloric Restriction
Carbon - metabolism
Cell Cycle - physiology
cell-nonautonomous
chronological life span
Culture Media
DNA Replication
Longevity
Metabolome
one-carbon metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - metabolism
serine
Serine - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA120.015402