Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics

Abstract

Age‐related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU‐dependent mitochondrial Ca2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70‐year‐old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU. Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES‐trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES‐dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial‐related proteins involved in Ca2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria‐related proteins as potential pharmacological targets to counteract age‐related muscle loss.

Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients: A Randomized Controlled Trial

“…MCU plays a significant role in skeletal muscle function, because it is responsible for Ca 2+ entry into mitochondria during muscle contraction . OPA1 controls mitochondrial fusion and effects on mitochondria respiratory efficiency . Both functions are crucial for mitochondrial function maintenance, and mitochondrial dysfunction associated with OPA1 leads to impaired ATP production and reduced force of skeletal muscle .…”

“…On an intracellular level, the EMS-dependent physiological effects on skeletal muscle size and force are associated with enhanced expression of mitochondrial calcium uniporter (MCU) and optic atrophy protein 1 (OPA1). MCU plays a significant role in skeletal muscle function, because it is responsible for Ca 21 entry into mitochondria during muscle contraction (16). OPA1 controls 25,50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur on the right side.…”

“…‡Coefficients for mean absolute change of muscle size at 25, 50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur on both sides. mitochondrial fusion (35) and effects on mitochondria respiratory efficiency (16). Both functions are crucial for mitochondrial function maintenance, and mitochondrial dysfunction associated with OPA1 leads to impaired ATP production and reduced force of skeletal muscle (32).…”

Relationship between strength and muscle mass in middle-aged and elderly women: a cross-sectional study

“…This quantitative decline coupled with the qualitative decline in the functionality and structure of the muscular system results in significant implications for the functional capacity of the elderly 33 . These modifications that occur in the muscular system due to the aging process impair the performance of motor skills, directly altering the ability of elderly individuals to perform instrumental and basic activities of daily living and making it difficult to adapt to the environment in which they live 27 .…”

Exercise effects on physiological function during aging

“…Optic atrophy 1 (OPA 1) also regulates fusion by shaping the level of inner-membrane ultrastructure and bioenergetics [46]. It has been shown that both electric stimulation and leg press training results in similar adaptation of skeletal muscle in aged subjects, which includes elevated levels of force generation, increased muscle mass, OPA1 and mitochondrial protein contents [47]. Kitaoka and co-workers reported that caloric restriction and endurance training together increased the levels of OPA1 and Mfn1 in rat skeletal muscle [48].…”