title: Impaired mitochondrial degradation by autophagy in the skeletal muscle of the aged female interleukin 10 null mouse.
abstract: Mitochondrial dysfunction, chronic inflammation and muscle aging are closely linked. Mitochondrial clearance is a process to dampen inflammation and is a critical pre-requisite to mitobiogenesis. The combined effect of aging and chronic inflammation on mitochondrial degradation by autophagy is understudied. In interleukin 10 null mouse (IL-10(tm/tm)), a rodent model of chronic inflammation, we studied the effects of aging and inflammation on mitochondrial clearance. We show that aging in IL-10(tm/tm) is associated with reduced skeletal muscle mitochondrial death signaling and altered formation of autophagosomes, compared to age-matched C57BL/6 controls. Moreover, skeletal muscles of old IL-10(tm/tm) mice have the highest levels of damaged mitochondria with disrupted mitochondrial ultrastructure and autophagosomes compared to all other groups. These observations highlight the interface between chronic inflammation and aging on altered mitochondrial biology in skeletal muscles.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Brookdale Department of Geriatrics and Palliative Medicine, USA. Electronic address: fred.ko@mssm.edu.
authors.forename: Fred
authors.initials: F
authors.lastname: Ko
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Abadir
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Marx
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, USA.
authors.forename: Reyhan
authors.initials: R
authors.lastname: Westbrook
authors.affiliation: Johns Hopkins University, Cellular and Molecular Medicine, Microscope Facility, Department of Medicine, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Cooke
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, USA.
authors.forename: Huanle
authors.initials: H
authors.lastname: Yang
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D005260:Female; D005838:Genotype; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000502:physiology / Q000648:ultrastructure; D063306:Mitophagy / Q000502:physiology*; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009220:Myositis / Q000473:pathology
chemical_list: D016753:Interleukin-10
keywords: Autophagy; IL-10; MIF; Mitochondria; NIX