Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice.

Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde produced from ethanol. A missense single nucleotide polymorphism (SNP) rs671 in exhibits a dominant-negative form of the ALDH2 protein. Nearly 40% of people in East Asia carry an inactive ALDH22 mutation. Previous studies reported that ALDH22 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.