Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction

Joseph M. Dhahbi, Tomoshi Tsuchiya, Hyon Jeen Kim, Patricia L. Mote, Stephen R. Spindler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Aging increases and caloric restriction (CR) decreases morbidity and mortality associated with the cardiovascular system. Using Affymetrix microarrays, we identified changes in heart gene expression induced by aging and CR in male mice. Eight weeks of CR (CR8) reproduced 19% of the long-term CR (LTCR)-related expression changes. Because CR8 begins to extend the life span of these mice, these genes may be keys to its cardioprotective effects. CR8 and LTCR changed gene expression in a manner consistent with reduced remodeling and fibrosis, and enhanced contractility and energy production via lipid β-oxidation. Molecular and histochemical studies indicated that CR reduced natriuretic peptide precursor type B and collagen expression, and reduced perivascular collagen deposition. We found smaller cardiomyocytes in the left ventricle of old-LTCR mice, suggesting reduced age-related cell death. Eight weeks of control feeding returned 97% of the LTCR-responsive genes to control expression levels. Thus, key CR-induced effects are rapidly responsive to diet, suggesting reduced caloric intake has rapid, positive effects on the heart.

Original languageEnglish
Pages (from-to)218-231
Number of pages14
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume61
Issue number3
DOIs
StatePublished - 2006/03

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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