Dysregulations of mitochondrial quality control and autophagic flux at an early age lead to progression of sarcopenia in SAMP8 mice.

Biogerontology
Hung-Wen LiuSue-Joan Chang

Abstract

The senescence-accelerated mouse (SAM) prone 8 (SAMP8) has been demonstrated for muscular aging research including sarcopenia, but its underlying mechanisms remain scarce. Physiological indices and histology of skeletal muscle were analyzed in SAMP8 mice at different ages. SAMP8 mice exhibited typical features of sarcopenia at 40 weeks of age and were more time-efficient than that at 88 weeks of age in bothSAM resistant 1 (SAMR1) and C57BL/6 mice. Increase in FoxO3a-mediated transcription of Atrogin-1 and MuRF1 and decrease in phosphorylated mTOR/P70s6k were observed at week 40 in SAMP8 mice. High oxidative stress was observed from week 24 and persisted to week 40 in SAMP8 mice evidenced by overexpression of protein carbonyl groups and reduced activities of CAT, SOD, and GPx. Downregulation of genes involved in mitochondrial biogenesis (PGC-1α, Nrf-1, Tfam, Ndufs8, and Cox5b) and in mitochondrial dynamics fission (Mfn2 and Opa1) from week 24 indicated dysregulation of mitochondrial quality control in SAMP8 mice. Impaired autophagic flux was observed in SAMP8 mice evidenced by elevated Atg13 and LC3-II accompanied with the accumulation of P62 and LAMP1. Increases in inflammatory factors (IL-6 and MCP-1), adipokines (leptin and r...Continue Reading

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Citations

Jan 5, 2021·Biological & Pharmaceutical Bulletin·Yasuyo MoritaMitsuhiko Miyamura
Jan 24, 2021·Experimental Gerontology·Frédéric N DaussinSteve Lancel
May 1, 2021·International Journal of Molecular Sciences·Laura DobladoMaria Monsalve
Aug 21, 2021·Scientific Reports·N CallizotP Verwaerde
Aug 28, 2021·International Journal of Molecular Sciences·Nicholas A ForemanLi Li Ji

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Methods Mentioned

BETA
electrophoresis
transmission electron microscopy

Software Mentioned

Sigma Plot
ImageJ

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