RRC ID 70074
Author Kasai A, Jee E, Tamura Y, Kouzaki K, Kotani T, Nakazato K.
Title Aldehyde dehydrogenase 2 deficiency promotes skeletal muscle atrophy in aged mice.
Journal Am J Physiol Regul Integr Comp Physiol
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.
Volume 322(6)
Pages R511-R525
Published 2022-6-1
DOI 10.1152/ajpregu.00304.2021
PMID 35318866
MeSH 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
IF 3.026
Mice RBRC05808