Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice
Akane Kasai, Eunbin Jee, Yuki Tamura, Karina Kouzaki, Takaya Kotani, Koichi Nakazato
Abstract
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.