Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice

Matthew L. Johnson, Antigoni Z. Lalia, Surendra Dasari, Maximilian Pallauf, Mark Fitch, Marc K. Hellerstein, Ian R Lanza

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 PUFAs) 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 PUFAs. 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 PUFAs.

Original languageEnglish (US)
Pages (from-to)734-743
Number of pages10
JournalAging Cell
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2015

Fingerprint

Eicosapentaenoic Acid
Docosahexaenoic Acids
Omega-3 Fatty Acids
Skeletal Muscle
Mitochondrial Proteins
Muscle Proteins
Anti-Inflammatory Agents
RNA Sequence Analysis
Post Translational Protein Processing
Unsaturated Fatty Acids
Proteomics
Inflammation

Keywords

  • Aging
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • Mitochondria
  • Omega 3
  • Proteomics
  • Sarcopenia

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice. / Johnson, Matthew L.; Lalia, Antigoni Z.; Dasari, Surendra; Pallauf, Maximilian; Fitch, Mark; Hellerstein, Marc K.; Lanza, Ian R.

In: Aging Cell, Vol. 14, No. 5, 01.10.2015, p. 734-743.

Research output: Contribution to journalArticle

Johnson, Matthew L. ; Lalia, Antigoni Z. ; Dasari, Surendra ; Pallauf, Maximilian ; Fitch, Mark ; Hellerstein, Marc K. ; Lanza, Ian R. / Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice. In: Aging Cell. 2015 ; Vol. 14, No. 5. pp. 734-743.
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