Exercise training initiated in late middle age attenuates cardiac fibrosis and advanced glycation end-product accumulation in senescent rats

Exp Gerontol. 2014 Feb;50:9-18. doi: 10.1016/j.exger.2013.11.006. Epub 2013 Nov 23.


While it has long been postulated that exercise training attenuates the age-related decline in heart function normally associated with increased fibrosis and collagen cross-linking, the potential benefits associated with exercise training initiated later in life are currently unclear. To address this question, Fischer 344 × Brown Norway F1 rats underwent treadmill-based exercise training starting in late middle age and continued into senescence (35 mo) and were compared with age-matched sedentary rats. Hearts were examined for fibrosis and advanced glycation end-products in the subendocardial layer of left ventricular cross-sections. Genes for collagen synthesis and degradation were assessed by polymerase chain reaction, and matrix metalloproteinase (MMP) activity was assessed by EnzChek® Gelatinase/Collagenase Assay Kit. Exercise training of late middle-aged rats attenuated fibrosis and collagen cross-linking, while also reducing age-related mortality between late middle age and senescence. This training was also associated with an attenuated advanced glycation end-product (AGE) accumulation with aging, suggesting a decrease in collagen cross-linking. Conversely, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression, TIMP and MMP1 protein expression, and MMP activity increased with age but were not significantly impacted by exercise training. While our results demonstrate that exercise training in late middle age attenuates age-related mortality and cardiac fibrosis and is accompanied by attenuated AGE accumulation indicative of less collagen cross-linking, the mechanisms explaining this attenuated replacement fibrosis did not appear to involve altered TIMP1 expression, or MMP protein and activity.

Keywords: %BF; AGE; ANOVA; Advanced glycation end-products; Aging; DXA; ECM; ET; Endurance exercise; F344BNF1; Fibrosis; Fischer 344 Brown Norway F1 hybrid rat; GAPDH; Heart; LV; MMP; Matrix metalloproteinases; RT-PCR; TIMP; TTBS; Tris-buffered saline (+0.5% Tween); WGA; advanced glycation end-product; analysis of variance; dual energy X-ray absorptiometry; exercise training; extracellular matrix; glyceraldehyde 3-phosphate dehydrogenase; left ventricle; matrix metalloproteinase; percent body fat; reverse transcription polymerase chain reaction; tissue inhibitor of matrix metalloproteinase; wheat germ agglutinin.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Collagen / metabolism
  • Fibrosis
  • Glycation End Products, Advanced / metabolism*
  • Matrix Metalloproteinases / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred F344
  • Survival Analysis
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism


  • Glycation End Products, Advanced
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Collagen
  • Matrix Metalloproteinases