3-B-P-042 〇細田 隆介¹、中島 龍汰¹、岩原 直敏²、野島 伊世里¹、久野 篤史¹ Ryusuke Hosoda¹, Ryuta Nakashima¹, Naotoshi Iwahara², Iyori Nojima¹, Atsushi Kuno^{1 1}札幌医科大・医、²札幌医科大・医・神経内科学講座 ¹Dept. Pharmacol., Sapporo Med. Univ. Sch. Med., ²Dept. Neurol., Sapporo Med. Univ. Sch. Med. Background:
Sarcopenia (age-related muscle loss) reduces healthspan. SIRT1 is a NAD⁺-dependent deacetylase. We reported increased protein acetylation and sarcopenia in aging and skeletal muscle specific SIRT1 knockout mice. SIRT1 activators suppress age-related sarcopenia and protein acetylation. This study aims to identify elevated acetylated proteins in aging and SIRT1 knockout muscles.
Methods and Results:  
Tibialis anterior from 10-19 week-old young wild-type (Young) and 81 week-old wild-type (Old) mice, and from 10-19 week-old wild-type (WT) and same-week-old SIRT1 knockout mice (SIRT1-MKO) were harvested. Acetylated peptides were identified by LC/MS/MS after immunoprecipitation with acetylated lysine antibody. Young/Old had 1213 acetylated peptides, and WT/SIRT1-MKO had 1879. Old vs. Young had 98 acetylated peptides, SIRT1-MKO vs. WT had 90 peptides with ≥1.5-fold increase (P<0.05). KEGG pathway and Gene Ontology analyses showed Old vs. Young acetylated proteins associated with TCA cycle, metabolic pathway, and fatty acid beta-oxidation. SIRT1-MKO had acetylated proteins associated with TCA cycle, metabolic pathway, nucleosome assembly, and muscle contraction. Commonly increased acetylated proteins in Old and SIRT1-MKO included many mitochondrial proteins.
Conclusions:
Aging or SIRT1 knockout skeletal muscles show increased acetylation of proteins involved in metabolism, those associated with the mitochondria. This increased acetylation may contribute to the pathogenesis of sarcopenia via reduced mitochondrial function.