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PGC‐1α Upregulates Mitochondrial Sirtuins and Reduces Protein Acetylation in Skeletal Muscle of Old Mice.
Author(s) -
Kang Choung Hun,
Yeo Dongwook,
Ji Li Li
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.713.7
Subject(s) - mitochondrial biogenesis , sirt3 , skeletal muscle , sirtuin , endocrinology , medicine , sirtuin 1 , mitochondrion , sarcopenia , coactivator , chemistry , messenger rna , receptor , biology , acetylation , downregulation and upregulation , gene , transcription factor , biochemistry
Mitochondrial dysfunction in skeletal muscle may contribute to decreased muscle mass, metabolic function and force generation during aging termed sarcopenia. Peroxisome proliferator‐activated receptor gamma coactivator 1 ‐alpha ( PGC ‐1α) and sirtuins are two groups of master regulators for mitochondrial biogenesis, dynamics and homeostasis. The purpose of the study was to investigate the effect of aging and PGC ‐1α overexpression (OE) on sirtuin gene expressions, protein acetylation and mitochondrial function in mouse skeletal muscle. Male C57BL mice at the age of 6 mo (young, Y; N=8), 12 mo (middle‐aged, M; N=8), and; and 24 mo (old, O; N=8) were transfected in vivo with either PGC‐1α DNA or GFP into the tibialis anterior (TA) muscle of one of their hindlimbs. Sirt1 mRNA expression was increased by 19% in M ( P <0.05), but decreased by 15% in O ( P <0.05), compared to Y, whereas PGC‐1α OE had no effect. Sirt3 mRNA level was lowered in M (28%, P <0.01) and O (56%, P <0.01) vs. Y; however, the level was restored by PGC‐1α by 24% ( P <0.05), 53% ( P <0.01) and 50% ( P <0.01) in Y, M, and O group, respectively. Further, Sirt5 mRNA level was reduced by ~60% in both M and O ( P <0.01), but increased with PGC‐1α by 26% ( P <0.05), 35% ( P <0.05) and 60% ( P <0.01) in Y, M and O, respectively. Sirt6 mRNA level was not affected by aging or PGC‐1α OE. Total cytoplasmic protein acetylation was 1.2‐fold higher in O vs. Y ( P <0.05), with no effect of PGC‐1α OE. Mitochondrial protein acetylation was increased 1.7‐fold in O vs. Y ( P <0.01), and suppressed by 22–28% ( P <0.05), in all age groups by PGC‐1α OE. Citrate synthase (CS) activity in M and O was 28 and 58% lower ( P <0.01), respectively, than that in Y. PGC‐1α OE increased CS activity by 14% ( P <0.05), 26% ( P <0.05) and 62% ( P <0.01) in Y, M and O, respectively. These data would suggest that aging reduces sirtuin family gene expression, whereas PGC‐1α OE can ameliorate mitochondrial function in older muscle by upregulating mitochondrial isoform Sirt3 and Sirt5 possibly due to their canonical role in promoting mitochondrial biogenesis.