Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

Age (Dordr). 2012 Jun;34(3):669-79. doi: 10.1007/s11357-011-9264-y. Epub 2011 May 18.

Abstract

Low mitochondriogenesis is critical to explain loss of muscle function in aging and in the development of frailty. The aim of this work was to explain the mechanism by which mitochondriogenesis is decreased in aging and to determine to which extent it may be prevented by exercise training. We used aged rats and compared them with peroxisome proliferator-activated receptor-γ coactivator-1α deleted mice (PGC-1α KO). PGC-1α KO mice showed a significant decrease in the mitochondriogenic pathway in muscle. In aged rats, we found a loss of exercise-induced expression of PGC-1α, nuclear respiratory factor-1 (NRF-1), and of cytochrome C. Thus muscle mitochondriogenesis, which is activated by exercise training in young animals, is not in aged or PGC-1α KO ones. Other stimuli to increase PGC-1α synthesis apart from exercise training, namely cold induction or thyroid hormone treatment, were effective in young rats but not in aged ones. To sum up, the low mitochondrial biogenesis associated with aging may be due to the lack of response of PGC-1α to different stimuli. Aged rats behave as PGC-1α KO mice. Results reported here highlight the role of PGC-1α in the loss of mitochondriogenesis associated with aging and point to this important transcriptional coactivator as a target for pharmacological interventions to prevent age-associated sarcopenia.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation, Developmental*
  • Male
  • Mice
  • Microscopy, Electron
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / ultrastructure
  • Organelle Biogenesis
  • Oxidative Stress / physiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Physical Conditioning, Animal / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Rats
  • Rats, Wistar
  • Sarcopenia / genetics
  • Sarcopenia / metabolism
  • Sarcopenia / pathology
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors