Life-long caloric restriction elicits pronounced protection of the aged myocardium: A role for AMPK

Andrew G. Edwards, Anthony J. Donato, Lisa A. Lesniewski, Rachel A. Gioscia, Douglas R. Seals, Russell L. Moore

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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 25/90. min 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.

Original languageEnglish (US)
Pages (from-to)739-742
Number of pages4
JournalMechanisms of Ageing and Development
Volume131
Issue number11-12
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Keywords

  • Diet
  • Ischemia
  • Myocardial infarction
  • Nutrition
  • Preconditioning

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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