Differential gene expression of FoxO1, ID1, and ID3 between young and older men and associations with muscle mass and function

Abstract

Aging is associated with significant losses of skeletal muscle mass and function. Numerous biochemical molecules have been implicated in the development of these age-related changes, however evidence from human models is sparse. Assessment of transcript expression is useful as it requires minimal tissue and may potentially be used in clinical trials. This study aimed to compare mRNA expression of proteolytic genes in skeletal muscle of young (18-35 yrs) and older (55-75 yrs) men. Muscle tissue was obtained from young (n=14, 21.35±1.03 yrs) and older (n=13, 63.85±1.83 yrs) men using percutaneous biopsy, and transcript expression was quantified using real-time polymerase chain reaction. Lower limb muscle mass was assessed using DEXA while concentric peak torque (PT) and power were assessed via isokinetic dynamometer. When age-related differences in mRNA expression were observed, Pearson correlation coefficients were obtained to examine the relationship of transcripts to muscle mass and function. Older muscle contained significantly more transcript for Forkhead Box O 1 (FoxO1, p=0.001), Inhibitor of DNA binding 1 (ID1, p=0.009), and Inhibitor of DNA Binding 3 (ID3, p=0.043) than young muscle. FoxO1 was significantly correlated with lean mass (R=-0.44, p=0.023) and PT (R=-0.40, p=0.046) while ID3 was significantly correlated with PT (R=-0.58, p=0.001) and power (R=-0.65, p<0.001). Moreover, ID1 was significantly correlated with all assessed measures of muscle function - mass (R=-0.39, p=0.046), PT (R=-0.53, p=0.005), and power (R=-0.520, p=0.005). These data suggest that FoxO1, ID1, and ID3 are potentially useful as clinical biomarkers of age-related muscle atrophy and dysfunction.