Aging is associated with altered estrogen receptor expression and alters redox protein balance in human female skeletal muscle

It has been hypothesized that age-related declines in skeletal muscle and vascular function in females may be partly estrogen-dependent. This study investigated skeletal muscle protein expression of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), and G protein-coupled estrogen receptor 1 (GPER1), and their association with proteins involved in redox regulation and vascular function, in relation to age, menopausal status, and lifelong physical activity. Skeletal muscle biopsies were obtained from 107 healthy females aged 19-70 years, including 26 postmenopausal females who were lifelong exercise trained. Protein expression of ER alpha, ER beta, GPER1, and downstream redox- and vascular-related proteins was quantified. Age- and menopause-related differences, associations between protein targets, and effects of lifelong exercise were examined. ER alpha protein expression was lower in older females with a 48% lower expression in the >= 55 years age group compared with the < 30-year group. GPER1 protein expression was 22% lower across all older age groups compared with the < 30-year group. ER beta expression was reduced in mid-life (45-59 years) but not in the oldest age group. Both ER alpha and ER beta were positively correlated with endothelial nitric oxide synthase (eNOS) expression, whereas GPER1 showed no association with eNOS. ER beta expression was associated with pro-oxidative NOX2 expression. Aging in females is associated with a lower ER alpha and GPER1 protein expression in skeletal muscle. Furthermore, lower ER expression by aging is associated with a lower eNOS expression, indicating associations with proteins involved in nitric oxide-related redox regulation in skeletal muscle in aged females.[GRAPHICS]