期刊
EXPERIMENTAL GERONTOLOGY
卷 46, 期 4, 页码 292-302出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2010.11.006
关键词
ACTN3; Muscle strength; Muscle mass; Metabolism; Fatigability
资金
- National Health and Medical Research Council [512254]
- Australian Postgraduate Award
Deficiency of the fast-twitch muscle protein alpha-actinin-3 due to homozygosity for a nonsense polymorphism (R577X) in the ACTN3 gene is common in humans. alpha-Actinin-3 deficiency (XX) is associated with reduced muscle strength/power and enhanced endurance performance in elite athletes and in the general population. The association between R577X and loss in muscle mass and function (sarcopenia) has previously been investigated in a number of studies in elderly humans. The majority of studies report loss of ACTN3 genotype association with muscle traits in the elderly, however, there is some indication that the XX genotype may be associated with faster muscle function decline. To further explore these potential age-related effects and the underlying mechanisms, we examined the effect of alpha-actinin-3 deficiency in aging male and female Actn3 knockout (KO) mice (2, 6, 12, and 18 months). Our findings support previous reports of a diminished influence of ACTN3 genotype on muscle performance in the elderly: genotype differences in intrinsic exercise performance, fast muscle force generation and male muscle mass were lost in aged mice, but were maintained for other muscle function traits such as grip strength. The loss of genotype difference in exercise performance occurred despite the maintenance of some slower muscle characteristics in KID muscles, such as increased oxidative metabolism and greater force recovery after fatigue. Interestingly, muscle mass decline in aged 18 month old male KO mice was greater compared to wild-type controls (WT) (-12.2% in KO; -6.5% in WT). These results provide further support that alpha-actinin-3 deficient individuals may experience faster decline in muscle function with increasing age. (C) 2010 Elsevier Inc. All rights reserved.
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