Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function

Abstract

Callahan DM, Tourville TW, Miller MS, Hackett SB, Sharma H, Cruickshank NC, Slauterbeck JR, Savage PD, Ades PA, Maughan DW, Beynnon BD, Toth MJ. Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function. Am J Physiol Cell Physiol 308: C932-C943, 2015. First published March 25, 2015; doi:10.1152/ajpcell.00014.2015.-In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n ϭ 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls (n ϭ 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in crosssectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men.Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems. mitochondria; physical activity; ultrastructure; myosin AGING AND DISEASE are frequently accompanied by reduced functional capacity and the development of physical disability (18). Reductions in physical activity with age are well documented (28,60,68) and promote chronic disease (31,44,53) and disability. As a result of their temporal coordination, it is difficult to disentangle the relative influence of age, disease, and physical inactivity on skeletal muscle biology and, in turn, the progression toward physical disability. Indeed, many of the muscle phenotypes that accompany aging and chronic disease, such as atrophy and contractile dysfunction, closely mimic those that accompany muscle disuse (1,46). Whether developed gradually or rapidly following a clinical event, muscle disuse in chronic conditions, such as heart failure or chronic obstructive pulmonary disease, is characterized by its persistent nature, as numerous studies reveal reduced habitual activity levels in these populations (28,60,68). Our understanding of the effects of chronic disuse on skeletal muscle size and structure is limited, in part, by the fact that it would be unethical to experimentally impose ...

Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

“…Nevertheless, gastrocnemius weight recovered only after 15 days of reloading following the seven-day immobilization period. As also shown in previous investigations [40,41], the sizes of both slow- and fast twitch muscle fibers were significantly smaller after seven days of immobilization than those observed in the 30-day non-immobilized control mice. Importantly, in both muscle fiber types, cross-sectional areas were similar to the control gastrocnemius following 15 days of reloading.…”

Reduced rate of knee extensor torque development in older adults with knee osteoarthritis is associated with intrinsic muscle contractile deficits

“…No group differences, nor group X sex interaction effects were found in the relative expression of MHC I, IIA or IIX via gel electrophoresis, as recently reported (12). Neither RTD, nor RTD rel , were related to the fractional expression of MHC I, IIA or IIA/X in the pooled cohort (range of r-values: −0.002 to 0.160; range of P-values: 0.52 to 0.99), in OA (range of r-values: 0.021 to 0.254; range of P-values: 0.36 to 0.94) or in controls (range of r-values: 0.011 to - 0.269; range of P-values: 0.35 to 0.97).…”

“…Additionally, 6 controls (4 men, 2 women) had hypertension and were on stable anti-hypertensive therapy, consisting of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (67%), diuretics (33%) and adrenergic blocking agents (17%). Data on skeletal muscle size and contractile function at the cellular and molecular levels for individuals with OA and controls (n=31) have recently been published (11, 12). Physical characteristics are reproduced to provide necessary descriptive information and muscle fiber size and functional data for the purposes of correlations analyses to assess determinants of RTD.…”

“…Whole muscle size was assessed using computerized tomography (CT) and dual energy xray absorptiometry (DEXA; GE Lunar Prodigy; Madison, WI) as described (12). Briefly, cross sectional area (CSA) of lean tissue (based on radiodensity) in the quadriceps muscle group were assessed by CT at mid-thigh.…”

The association of waist circumference with walking difficulty among adults with or at risk of knee osteoarthritis: the Osteoarthritis Initiative

“…The following baseline factors were considered as potential confounders based on existing literature linking them to function: age 23 , sex (men/women) 24 , race (White, other) 25 , education (some college/< high School) 26 , and self-reported physical activity (Physical Activity Scale of the Elderly) 27 . We also employed disease status as a potential confounder defined as no radiographic knee osteoarthritis (ROA), presence of ROA, or the presence of symptomatic knee OA, i.e., the presence of ROA and knee pain (Table 1).…”