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

Autor: Elisa Enriquez-Hesles, Margaret B. Wierman, Ryan D. Fine, Sean M. Santos, Daniel L. Smith, Nazif Maqani, James R. Bain, Agata Kalita, Matthew D. Hirschey, Matthew D. Sutcliffe, Jeffrey S. Smith, John L. Hartman, Kevin A. Janes, Michael J. Muehlbauer
Rok vydání: 2020
Předmět:
0301 basic medicine
RT
retention time
Cell
QTL
quantitative trait locus
Biochemistry
cell-nonautonomous
chemistry.chemical_compound
AMP-activated protein kinase
chronological life span
media_common
chemistry.chemical_classification
Growth medium
biology
Cell Cycle
Longevity
TOR
target of rapamycin
Amino acid
Cell biology
medicine.anatomical_structure
CFUs
colony forming units
Metabolome
TCA
tricarboxylic acid cycle
Research Article
DNA Replication
CR
caloric restriction
media_common.quotation_subject
Saccharomyces cerevisiae
CRCM
CR conditioned media
serine
03 medical and health sciences
SC
synthetic complete
medicine
NR
nonrestricted
GAAC
general amino acid control
Molecular Biology
CLS
chronological life span
Caloric Restriction
amino acids
030102 biochemistry & molecular biology
aging
Cell Biology
biology.organism_classification
one-carbon metabolism
Yeast
Carbon
Culture Media
Citric acid cycle
AMPK
AMP-activated protein kinase
BCAA
branched chain amino acids
030104 developmental biology
chemistry
biology.protein
Zdroj: The Journal of Biological Chemistry
ISSN: 1083-351X
Popis: 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.
Databáze: OpenAIRE
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