Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice

Am J Physiol Regul Integr Comp Physiol. 2022 Jun 1;322(6):R511-R525. doi: 10.1152/ajpregu.00304.2021. Epub 2022 Mar 23.

Abstract

Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde produced from ethanol. A missense single nucleotide polymorphism (SNP) rs671 in ALDH2 exhibits a dominant-negative form of the ALDH2 protein. Nearly 40% of people in East Asia carry an inactive ALDH2*2 mutation. Previous studies reported that ALDH2*2 is associated with increased risk of several diseases. In this study, we examined the effect of ALDH2 deficiency on age-related muscle atrophy and its underlying mechanisms. We found that ALDH2 deficiency promotes age-related loss of muscle fiber cross-sectional areas, especially in oxidative fibers. Furthermore, ALDH2 deficiency exacerbated age-related accumulation of 4-hydroxy-2-nonenal (4-HNE), a marker of oxidative stress in the gastrocnemius muscle. Similarly, mitochondrial reactive oxygen species (ROS) production increased in aged ALDH2-knockout mice, indicating that ALDH2 deficiency induced mitochondrial dysfunction. In summary, ALDH2 deficiency promotes age-related muscle loss, especially in oxidative fibers, which may be associated with an increased accumulation of oxidative stress via mitochondrial dysfunction.

Keywords: ALDH2; aging; aldehyde dehydrogenase 2; oxidative fibers; skeletal muscle.

MeSH terms

  • Aldehyde Dehydrogenase, Mitochondrial / genetics
  • Aldehyde Dehydrogenase, Mitochondrial / metabolism
  • Animals
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal* / metabolism
  • Muscular Atrophy* / genetics
  • Muscular Atrophy* / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • ALDH2 protein, human
  • ALDH2 protein, mouse
  • Aldehyde Dehydrogenase, Mitochondrial