Document Detail

Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK.
MedLine Citation:
PMID:  20934448     Owner:  NLM     Status:  MEDLINE    
Short-term caloric restriction (CR) protects the young myocardium against ischemia/reperfusion (I/R) injury through a mechanism involving AMP-activated protein kinase (AMPK). Here we ask whether a life-long CR intervention can extend this protection to the aged myocardium, and whether AMP-activated protein kinase (AMPK) plays a role in that protection. Hearts from ad libitum fed (AL) and life-long calorically restricted (LCR) mice were examined at 30 months of age by 25/90min global I/R, with and without AMPK inhibition (AraA). LCR hearts were protected from infarction (AL, 28±4% vs. LCR, 10±1%, p<0.01) and post-ischemic functional deficit (LVDP recovery: AL, 65±8% vs. LCR, 93±7%, p<0.01). Pre-ischemic AraA impaired both of these protective effects (Infarct size: LCR+AraA, 22±4%; LVDP recovery: LCR+AraA, 82±9%, both p vs. AL >0.1). AMPKα phosphorylation was dramatically increased in LCR hearts prior to I/R (AL, 1.18±0.01 vs. LCR, 1.68±0.04, ratio, p<0.0001), and accompanied by a more modest increase in total AMPKα (AL, 2.18±0.03 vs. LCR, 2.39±0.08 ratio, p<0.05). These results indicate that life-long caloric restriction profoundly protects the aged heart against I/R injury, and suggest that AMPK may play a role in that protection.
Andrew G Edwards; Anthony J Donato; Lisa A Lesniewski; Rachel A Gioscia; Douglas R Seals; Russell L Moore
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-08
Journal Detail:
Title:  Mechanisms of ageing and development     Volume:  131     ISSN:  1872-6216     ISO Abbreviation:  Mech. Ageing Dev.     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-03-21     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0347227     Medline TA:  Mech Ageing Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  739-42     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
AMP-Activated Protein Kinases / antagonists & inhibitors,  metabolism,  physiology*
Aging / physiology*
Caloric Restriction*
Myocardial Reperfusion Injury / enzymology,  prevention & control*
Myocardium / enzymology*
Grant Support
AG013038/AG/NIA NIH HHS; K01 AG033196/AG/NIA NIH HHS; KO1-AG029337/AG/NIA NIH HHS; KO1-AG033196-01/AG/NIA NIH HHS; R01 HL072790/HL/NHLBI NIH HHS; R21 AG033755/AG/NIA NIH HHS; R37 AG013038/AG/NIA NIH HHS
Reg. No./Substance:
EC Protein Kinases; EC alpha1 subunit, mouse

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