PMID- 22810224
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 37
DP  - 2012 Sep 7
TI  - Enhanced energy metabolism contributes to the extended life span of 
      calorie-restricted Caenorhabditis elegans.
PG  - 31414-26
LID - 10.1074/jbc.M112.377275 [doi]
AB  - Caloric restriction (CR) markedly extends life span and improves the health of a 
      broad number of species. Energy metabolism fundamentally contributes to the 
      beneficial effects of CR, but the underlying mechanisms that are responsible for 
      this effect remain enigmatic. A multidisciplinary approach that involves 
      quantitative proteomics, immunochemistry, metabolic quantification, and life span 
      analysis was used to determine how CR, which occurs in the Caenorhabditis elegans 
      eat-2 mutants, modifies energy metabolism of the worm, and whether the observed 
      modifications contribute to the CR-mediated physiological responses. A switch to 
      fatty acid metabolism as an energy source and an enhanced rate of energy 
      metabolism by eat-2 mutant nematodes were detected. Life span analyses validated 
      the important role of these previously unknown alterations of energy metabolism 
      in the CR-mediated longevity of nematodes. As observed in mice, the 
      overexpression of the gene for the nematode analog of the cytosolic form of 
      phosphoenolpyruvate carboxykinase caused a marked extension of the life span in 
      C. elegans, presumably by enhancing energy metabolism via an altered rate of 
      cataplerosis of tricarboxylic acid cycle anions. We conclude that an increase, 
      not a decrease in fuel consumption, via an accelerated oxidation of fuels in the 
      TCA cycle is involved in life span regulation; this mechanism may be conserved 
      across phylogeny.
FAU - Yuan, Yiyuan
AU  - Yuan Y
AD  - Department of Pharmacology, School of Medicine, Case Western Reserve University, 
      Cleveland, Ohio 44106, USA.
FAU - Kadiyala, Chandra S
AU  - Kadiyala CS
FAU - Ching, Tsui-Ting
AU  - Ching TT
FAU - Hakimi, Parvin
AU  - Hakimi P
FAU - Saha, Sudipto
AU  - Saha S
FAU - Xu, Hua
AU  - Xu H
FAU - Yuan, Chao
AU  - Yuan C
FAU - Mullangi, Vennela
AU  - Mullangi V
FAU - Wang, Liwen
AU  - Wang L
FAU - Fivenson, Elayne
AU  - Fivenson E
FAU - Hanson, Richard W
AU  - Hanson RW
FAU - Ewing, Rob
AU  - Ewing R
FAU - Hsu, Ao-Lin
AU  - Hsu AL
FAU - Miyagi, Masaru
AU  - Miyagi M
FAU - Feng, Zhaoyang
AU  - Feng Z
LA  - eng
GR  - P20 CA103736/CA/NCI NIH HHS/United States
GR  - R01 AG028516/AG/NIA NIH HHS/United States
GR  - P20-CA-103736/CA/NCI NIH HHS/United States
GR  - 1R01 AG028516/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 - 20120718
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Eat-2 protein, C elegans)
RN  - 0 (Receptors, Nicotinic)
SB  - IM
MH  - Animals
MH  - Caenorhabditis elegans/genetics/*metabolism
MH  - Caenorhabditis elegans Proteins/genetics/metabolism
MH  - *Caloric Restriction
MH  - Citric Acid Cycle/*physiology
MH  - Longevity/*physiology
MH  - Mutation
MH  - Oxidation-Reduction
MH  - Receptors, Nicotinic/genetics/metabolism
PMC - PMC3438970
EDAT- 2012/07/20 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/09/07
CRDT- 2012/07/20 06:00
PHST- 2012/07/20 06:00 [entrez]
PHST- 2012/07/20 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/09/07 00:00 [pmc-release]
AID - S0021-9258(20)63085-X [pii]
AID - M112.377275 [pii]
AID - 10.1074/jbc.M112.377275 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Sep 7;287(37):31414-26. doi: 10.1074/jbc.M112.377275. Epub 2012 
      Jul 18.