Aging alters acetylation status in skeletal and cardiac muscles

Dongwook Yeo, Chounghun Kang, Li Li Ji

Research output: Contribution to journalArticle

Abstract

During aging, organs such as skeletal muscle and heart require sufficient NAD+ both as a coenzyme for oxidative-reductive electron transfer and as a substrate for multiple signaling pathways. Sirtuins (SIRTs), a family of NAD+-dependent deacetylase, play an important role in regulating mitochondrial homeostasis and antioxidant defense by deacetylating transcription factors and enzymes such as PGC-1α, p65, GCN5, and SOD2. However, age-related DNA damage and increased SASP activate PARP-1 and CD38, the enzymes competing with SIRTs for NAD+. Thus, it is important to know how aging alters intracellular NAD+ status and NAD+-depending enzyme expression in muscles. In this study, we report that the acetylation level of muscle protein pool, as well as major SIRTs target proteins (PGC-1α, GCN5, p65, and SOD2), was significantly increased in hindlimb and cardiac muscles of 24-month old mice compared with their 6-month old counterparts, despite the fact that most members of the SIRT family were upregulated with aging. Aging increased the protein content of PARP-1 and CD38, whereas decreased NAD+ levels in both skeletal and heart muscles. Aged muscles demonstrated clear signs of mitochondrial dysfunction, oxidative stress, and inflammation. Taken together, our data suggest that despite the upregulation of SIRTs, aged muscles suffered from NAD+ deficit partly due to the competition of elevated CD38 and PARP-1. The enhanced acetylation of several key proteins involved in broad cellular functions may contribute to the age-related muscle deterioration.

Original languageEnglish (US)
Pages (from-to)963-976
Number of pages14
JournalGeroScience
Volume42
Issue number3
DOIs
StatePublished - Jun 1 2020

Keywords

  • Aging
  • CD38
  • Deacetylation
  • NAD
  • PARP
  • SIRT
  • Skeletal muscle

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