Age-related cardiac muscle sarcopenia: Combining experimental and mathematical modeling to identify mechanisms

Jing Lin, Elizabeth F. Lopez, Yufang Jin, Holly Van Remmen, Terry Bauch, Hai Chao Han, Merry L. Lindsey

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Age-related skeletal muscle sarcopenia has been extensively studied and smooth muscle sarcopenia has been recently described, but age-related cardiac sarcopenia has not been previously examined. Therefore, we evaluated adult (7.5 ± 0.5 months; n = 27) and senescent (31.8 ± 0.4 months; n = 26) C57BL/6J mice for cardiac sarcopenia using physiological, histological, and biochemical assessments. Mice do not develop hypertension, even into senescence, which allowed us to decouple vascular effects and monitor cardiac-dependent variables. We then developed a mathematical model to describe the relationship between age-related changes in cardiac muscle structure and function. Our results showed that, compared to adult mice, senescent mice demonstrated increased left ventricular (LV) end diastolic dimension, decreased wall thickness, and decreased ejection fraction, indicating dilation and reduced contractile performance. Myocyte numbers decreased, and interstitial fibrosis was punctated but doubled in the senescent mice, indicating reparative fibrosis. Electrocardiogram analysis showed that PR interval and QRS interval increased and R amplitude decreased in the senescent mice, indicating prolonged conduction times consistent with increased fibrosis. Intracellular lipid accumulation was accompanied by a decrease in glycogen stores in the senescent mice. Mathematical simulation indicated that changes in LV dimension, collagen deposition, wall stress, and wall stiffness precede LV dysfunction. We conclude that age-related cardiac sarcopenia occurs in mice and that LV remodeling due to increased end diastolic pressure could be an underlying mechanism for age-related LV dysfunction.

Original languageEnglish (US)
Pages (from-to)296-306
Number of pages11
JournalExperimental Gerontology
Volume43
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Aging
  • Cardiac
  • Fibrosis
  • Hypertrophy
  • Sarcopenia

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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