title: Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging.
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 PGC1α 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 musclevs.heart during aging.
authors.affiliation: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Science, Nanyang Technological University, Singapore 637551.
authors.forename: Shu Yun
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lim
authors.affiliation: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857.
authors.forename: Brijesh K
authors.initials: BK
authors.lastname: Singh
authors.affiliation: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857.
authors.forename: Rohit A
authors.initials: RA
authors.lastname: Sinha
authors.affiliation: Department of Molecular Medicine, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.|Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Salmon
authors.affiliation: Program of Cardiovascular and Metabolic Disorders, Duke-NUS Medical School Singapore, Singapore 169857.|Duke Molecular Physiology Institute, Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018832:Molecular Chaperones
keywords: aging; autophagy; ceramide; chaperone-mediated autophagy (CMA); fatty acid oxidation; heart; muscle