PMID- 24612461
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 13
IP  - 3
DP  - 2014 Jun
TI  - Altered proteome turnover and remodeling by short-term caloric restriction or 
      rapamycin rejuvenate the aging heart.
PG  - 529-39
LID - 10.1111/acel.12203 [doi]
AB  - Chronic caloric restriction (CR) and rapamycin inhibit the mechanistic target of 
      rapamycin (mTOR) signaling, thereby regulating metabolism and suppressing protein 
      synthesis. Caloric restriction or rapamycin extends murine lifespan and 
      ameliorates many aging-associated disorders; however, the beneficial effects of 
      shorter treatment on cardiac aging are not as well understood. Using a recently 
      developed deuterated-leucine labeling method, we investigated the effect of 
      short-term (10 weeks) CR or rapamycin on the proteomics turnover and remodeling 
      of the aging mouse heart. Functionally, we observed that short-term CR and 
      rapamycin both reversed the pre-existing age-dependent cardiac hypertrophy and 
      diastolic dysfunction. There was no significant change in the cardiac global 
      proteome (823 proteins) turnover with age, with a median half-life 9.1 days in 
      the 5-month-old hearts and 8.8 days in the 27-month-old hearts. However, proteome 
      half-lives of old hearts significantly increased after short-term CR (30%) or 
      rapamycin (12%). This was accompanied by attenuation of age-dependent protein 
      oxidative damage and ubiquitination. Quantitative proteomics and pathway analysis 
      revealed an age-dependent decreased abundance of proteins involved in 
      mitochondrial function, electron transport chain, citric acid cycle, and fatty 
      acid metabolism as well as increased abundance of proteins involved in glycolysis 
      and oxidative stress response. This age-dependent cardiac proteome remodeling was 
      significantly reversed by short-term CR or rapamycin, demonstrating a concordance 
      with the beneficial effect on cardiac physiology. The metabolic shift induced by 
      rapamycin was confirmed by metabolomic analysis.
CI  - (c) 2014 The Authors. Aging Cell Published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - Dai, Dao-Fu
AU  - Dai DF
AD  - Department of Pathology, University of Washington, 1959 NE Pacific Ave, Seattle, 
      WA, 98195, USA.
FAU - Karunadharma, Pabalu P
AU  - Karunadharma PP
FAU - Chiao, Ying A
AU  - Chiao YA
FAU - Basisty, Nathan
AU  - Basisty N
FAU - Crispin, David
AU  - Crispin D
FAU - Hsieh, Edward J
AU  - Hsieh EJ
FAU - Chen, Tony
AU  - Chen T
FAU - Gu, Haiwei
AU  - Gu H
FAU - Djukovic, Danijel
AU  - Djukovic D
FAU - Raftery, Daniel
AU  - Raftery D
FAU - Beyer, Richard P
AU  - Beyer RP
FAU - MacCoss, Michael J
AU  - MacCoss MJ
FAU - Rabinovitch, Peter S
AU  - Rabinovitch PS
LA  - eng
GR  - P41 GM103533/GM/NIGMS NIH HHS/United States
GR  - R01 HL101186/HL/NHLBI NIH HHS/United States
GR  - P01 AG001751/AG/NIA NIH HHS/United States
GR  - T32 AG000057/AG/NIA NIH HHS/United States
GR  - P30 DK035816/DK/NIDDK NIH HHS/United States
GR  - P30 AG013280/AG/NIA NIH HHS/United States
GR  - R01 AG038550/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 - 20140225
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Proteome)
RN  - AR09D82C7G (Deuterium)
RN  - GMW67QNF9C (Leucine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - *Caloric Restriction
MH  - Cardiovascular Diseases/metabolism
MH  - Deuterium
MH  - Female
MH  - Heart/drug effects/*physiology
MH  - Leucine/administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/*metabolism
MH  - Proteome/*metabolism
MH  - Random Allocation
MH  - Sirolimus/*pharmacology
MH  - Ventricular Remodeling/drug effects/physiology
PMC - PMC4040127
MID - NIHMS558375
OTO - NOTNLM
OT  - caloric restriction
OT  - cardiac aging
OT  - dynamics
OT  - proteomics
OT  - rapamycin
EDAT- 2014/03/13 06:00
MHDA- 2015/03/31 06:00
PMCR- 2014/06/01
CRDT- 2014/03/12 06:00
PHST- 2014/01/05 00:00 [accepted]
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - 10.1111/acel.12203 [doi]
PST - ppublish
SO  - Aging Cell. 2014 Jun;13(3):529-39. doi: 10.1111/acel.12203. Epub 2014 Feb 25.