Open AccessEicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice
Author(s) -
Johnson Matthew L.,
Lalia Antigoni Z.,
Dasari Surendra,
Pallauf Maximilian,
Fitch Mark,
Hellerstein Marc K.,
Lanza Ian R.
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12352
Subject(s) - docosahexaenoic acid , biology , eicosapentaenoic acid , skeletal muscle , oxidative phosphorylation , mitochondrion , biochemistry , oxidative stress , medicine , endocrinology , fatty acid , polyunsaturated fatty acid
Summary Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age‐related declines in physical function. Early evidence suggests that dietary omega‐3 polyunsaturated fatty acids (n‐3 PUFA s) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid ( EPA ) supplementation partially attenuated the age‐related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid ( DHA ). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large‐scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post‐translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age‐related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti‐inflammatory properties of n‐3 PUFA s. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti‐inflammatory, reduced FXR / RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n‐3 PUFA s.