Review Article

Aging, exercise, and extracellular matrix in the heart


Hyo-Bum Kwak

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Aging is characterized by a progressive impairment of (a) cardiac struc-ture including fibrosis and cardiomyocyte density, and (b) cardiac func-tion including stroke volume, ejection fraction, and cardiac output. The cardiac remodeling involves loss of cardiac myocytes, reactive hyper-trophy of the remaining cells, and increased extracellular matrix (ECM) and fibrosis in the aging heart, especially left ventricles. Fibrosis (i.e., accumulation of collagen) with aging is very critical in impairing cardiac function associated with increased myocardial stiffness. The balance of ECM remodeling via ECM synthesis and degradation is essential for normal cardiac structure and function. Thus an understanding of up-stream ECM regulatory factors such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and myofibro-blasts is necessary for gaining new insights into managing cardiac re-modeling and dysfunction with aging. In contrast, exercise training ef-fectively improves cardiac function in both young and older individuals. Exercise training also improves maximal cardiovascular function by in -creasing stroke volume and cardiac output. However, limited data indi-cate that exercise training might attenuate collagen content and re-modeling in the aging heart. We recently found that 12 weeks of exer-cise training protected against geometric changes of collagen ECM in the aging heart and ameliorated age-associated dysregulation of ECM in the heart, as indicated by up-regulation of active MMPs as well as down-regulation of TIMPs and TGF-β. This review will provide a sum-mary and discussion of aging and exercise effects on fibrosis and up-stream regulators of ECM in the heart.


  Cardiac MMPs and TIMPs
  Cardiac TNF-α
  Cardiac TGF-β
  Cardiac myofibroblasts
  Aging and cardiac collagens
  Exercise and cardiac collagens


  • Hyo-Bum Kwak Department of Kinesiology, Inha University, Incheon, Korea


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