Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging

Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K. Singh, Rohit A. Sinha, Adam B. Salmon, Paul M. Yen

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1a also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging.

Original languageEnglish (US)
Pages (from-to)583-599
Number of pages17
JournalAging
Volume9
Issue number2
DOIs
StatePublished - 2017

Keywords

  • Aging
  • Autophagy
  • Ceramide
  • Chaperone-mediated autophagy (CMA)
  • Fatty acid oxidation
  • Heart
  • Muscle

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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