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Promotion of oxidative stress is associated with mitochondrial dysfunction and muscle atrophy in aging mice
Author(s) -
Kadoguchi Tomoyasu,
Shimada Kazunori,
Miyazaki Tetsuro,
Kitamura Kenichi,
Kunimoto Mitsuhiro,
Aikawa Tatsuro,
Sugita Yurina,
Ouchi Shohei,
Shiozawa Tomoyuki,
YokoyamaNishitani Miho,
Fukao Kosuke,
Miyosawa Katsutoshi,
Isoda Kikuo,
Daida Hiroyuki
Publication year - 2020
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/ggi.13818
Subject(s) - nicotinamide adenine dinucleotide phosphate , endocrinology , medicine , oxidative stress , tfam , muscle atrophy , skeletal muscle , mitochondrial biogenesis , mitochondrion , biology , oxidase test , biochemistry , enzyme
Aim We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. Methods We used 6‐, 12‐ and 24‐month (6 M, 12 M and 24 M)‐old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real‐time polymerase chain reaction, immunoblotting and histological analyses. Results The muscle weight and myocyte cross‐sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4‐hydroxy‐2‐nonenal and 3‐nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC)‐α, peroxisome proliferator‐activated receptor gamma coactivator‐1β, sirtuin‐1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin–proteasome pathway genes muscle ring finger‐1 and atrogin‐1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated‐Akt and ‐p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). Conclusions These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78–84 .