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• W2898849960 abstract "Mitochondrial dysfunction plays an important role in the etiology of age-related muscle atrophy known as sarcopenia. PGC-1α is positioned at the center of crosstalk in regulating mitochondrial quality control, but its role in mitophagy in aged skeletal muscle is currently unclear. The present study investigated the effects of aging and PGC-1α overexpression via in vivo DNA transfection on key mitophagy protein markers, as well as mitochondrial dynamics related proteins, metabolic function and antioxidant capacity in mouse muscle. C57BL/6J mice at the age of 2 mo (young, Y; N = 14) and 24 mo (old, O; N = 14) were transfected in vivo with either PGC-1α DNA (OE, N = 7) or GFP (N = 7) into the tibialis anterior (TA) muscle followed by electroporation. PINK1 and Parkin protein contents were 3.6 and 1.4-fold higher (P < 0.01), whereas mitochondrial ubiquitination (Ub) increased 1.5-fold (P < 0.05), in O vs. Y mice. PGC-1 OE suppressed PINK and Parkin protein levels by 50–60% (P < 0.01), and decreased Ub by 20% (P < 0.05) in old mice. Aging significantly increased the protein content of LC3II (30%, P < 0.05), p62 (42%, P < 0.05), RheB (5.5-fold, P < 0.01), Beclin-1 (3-fold, P < 0.01) and Mfn2 (~4-fold, P < 0.01) in the TA muscle. However, these age-related increases in mitophagy markers were attenuated by PGC-1α OE. Furthermore, aging dramatically increased Fis-1 protein content by 14-fold (P < 0.01), along with a severe reduction of citrate synthase activity (64%, P < 0.01) and cytochrome c oxidase subunit IV (COXIV) protein content (85%, P < 0.01). PGC-1α OE mitigated the age effects on Fis-1 and Drp-1 (P < 0.05). Moreover, PGC-1α OE enhanced mitochondrial oxidative function and antioxidant enzyme activities, and decreased lipid peroxidation and inner membrane damage found in old mice (P < 0.01). In summary, our data demonstrate that mitophagy protein expression in skeletal muscle was enhanced at old age driven possibly by increased mitochondrial dysfunction, damage, and fission. PGC-1α OE was effective in ameliorating mitochondrial deficits but did not restore muscle fiber atrophy." @default.
• W2898849960 created "2018-11-09" @default.
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• W2898849960 date "2019-01-01" @default.
• W2898849960 modified "2023-09-29" @default.
• W2898849960 title "Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo" @default.
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• W2898849960 doi "https://doi.org/10.1016/j.freeradbiomed.2018.10.456" @default.
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