PMID- 33243834
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20240229
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 296
DP  - 2021 Jan-Jun
TI  - A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric 
      restriction and one-carbon metabolism.
PG  - 100125
LID - S0021-9258(20)00116-7 [pii]
LID - 10.1074/jbc.RA120.015402 [doi]
LID - 100125
AB  - 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.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Enriquez-Hesles, Elisa
AU  - Enriquez-Hesles E
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA.
FAU - Smith, Daniel L Jr
AU  - Smith DL Jr
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA; Department of Nutrition Science, 
      Nathan Shock Center of Excellence in the Basic Biology of Aging, University of 
      Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Maqani, Nazif
AU  - Maqani N
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA.
FAU - Wierman, Margaret B
AU  - Wierman MB
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA.
FAU - Sutcliffe, Matthew D
AU  - Sutcliffe MD
AD  - Department of Biomedical Engineering, University of Virginia School of Medicine, 
      Charlottesville, Virginia, USA.
FAU - Fine, Ryan D
AU  - Fine RD
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA.
FAU - Kalita, Agata
AU  - Kalita A
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA.
FAU - Santos, Sean M
AU  - Santos SM
AD  - Department of Genetics, Nutrition and Obesity Research Center, Nathan Shock 
      Center of Excellence in the Basic Biology of Aging, University of Alabama at 
      Birmingham, Birmingham, Alabama, USA.
FAU - Muehlbauer, Michael J
AU  - Muehlbauer MJ
AD  - Department of Medicine, Duke Molecular Physiology Institute, Duke University, 
      Durham, North Carolina, USA.
FAU - Bain, James R
AU  - Bain JR
AD  - Department of Medicine, Duke Molecular Physiology Institute, Duke University, 
      Durham, North Carolina, USA.
FAU - Janes, Kevin A
AU  - Janes KA
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA; Department of Biomedical 
      Engineering, University of Virginia School of Medicine, Charlottesville, 
      Virginia, USA.
FAU - Hartman, John L 4th
AU  - Hartman JL 4th
AD  - Department of Genetics, Nutrition and Obesity Research Center, Nathan Shock 
      Center of Excellence in the Basic Biology of Aging, University of Alabama at 
      Birmingham, Birmingham, Alabama, USA.
FAU - Hirschey, Matthew D
AU  - Hirschey MD
AD  - Department of Medicine, Duke Molecular Physiology Institute, Duke University, 
      Durham, North Carolina, USA.
FAU - Smith, Jeffrey S
AU  - Smith JS
AD  - Department of Biochemistry and Molecular Genetics, University of Virginia School 
      of Medicine, Charlottesville, Virginia, USA. Electronic address: 
      jss5y@virginia.edu.
LA  - eng
GR  - T32 GM007267/GM/NIGMS NIH HHS/United States
GR  - R56 AG059590/AG/NIA NIH HHS/United States
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
GR  - R01 AG045351/AG/NIA NIH HHS/United States
GR  - R01 GM075240/GM/NIGMS NIH HHS/United States
GR  - R01 AG043076/AG/NIA NIH HHS/United States
GR  - R01 CA214718/CA/NCI NIH HHS/United States
GR  - F30 AG067760/AG/NIA NIH HHS/United States
GR  - R21 AG053596/AG/NIA NIH HHS/United States
GR  - T32 GM008136/GM/NIGMS NIH HHS/United States
GR  - T32 GM139787/GM/NIGMS NIH HHS/United States
GR  - P30 DK056336/DK/NIDDK NIH HHS/United States
GR  - P30 AG028716/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201202
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Culture Media)
RN  - 452VLY9402 (Serine)
RN  - 7440-44-0 (Carbon)
SB  - IM
MH  - *Caloric Restriction
MH  - Carbon/*metabolism
MH  - Cell Cycle/physiology
MH  - Culture Media
MH  - DNA Replication
MH  - Longevity
MH  - Metabolome
MH  - Saccharomyces cerevisiae/cytology/growth & development/*metabolism
MH  - Serine/*metabolism
PMC - PMC7949035
OTO - NOTNLM
OT  - Saccharomyces cerevisiae
OT  - aging
OT  - amino acids
OT  - caloric restriction
OT  - cell-nonautonomous
OT  - chronological life span
OT  - one-carbon metabolism
OT  - serine
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2020/11/28 06:00
MHDA- 2021/08/19 06:00
PMCR- 2020/12/02
CRDT- 2020/11/27 05:38
PHST- 2020/07/27 00:00 [received]
PHST- 2020/10/26 00:00 [revised]
PHST- 2020/11/25 00:00 [accepted]
PHST- 2020/11/28 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/11/27 05:38 [entrez]
PHST- 2020/12/02 00:00 [pmc-release]
AID - S0021-9258(20)00116-7 [pii]
AID - 100125 [pii]
AID - 10.1074/jbc.RA120.015402 [doi]
PST - ppublish
SO  - J Biol Chem. 2021 Jan-Jun;296:100125. doi: 10.1074/jbc.RA120.015402. Epub 2020 
      Dec 2.