Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats

Abstract

We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16–17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW−). The 9 RW+ rats averaged 83 m/day (range: 8–163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW− rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle.

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

“…Although an age-related decline in voluntary wheel running is well documented in mice and rats [19, 20], relatively small amounts of physical activity (≤1 km per day) can have many benefits [21–23]. Beyond the protection of muscle mass [19], long-term voluntary wheel running (ranging from 1 to 31 m) has a variety of physiological benefits including decreased weight gain [23, 24], restoration of neuromuscular junction (NMJ) architecture, and preserved muscle innervation [21, 25], increased mitochondrial biogenesis and autophagy [22, 26–28], improved oxygen uptake (VO 2 max) [22], and the overall metabolic enhancement of the skeletal muscle [29]. …”

Impact of Exercise and Aging on Rat Urine and Blood Metabolome. An LC-MS Based Metabolomics Longitudinal Study

“…A small number of studies examines the combined effect of aging and exercise, both of which represent strong metabolome modifiers in rodents [37,38,39,40,41,42]. Of these studies, only one employed metabolomics [42].…”

Exercise reverses pain-related weight asymmetry and differentially modulates trabecular bone microarchitecture in a rat model of osteoarthritis

“…Voluntary wheel running in rodents has been shown to enhance muscle viability and bone strength [7–9], attenuate allodynia and elevated IL-1β levels in a model of neuropathic pain [10], and increase protective CD206 macrophage production in a model of muscle pain, and decrease pain- and stress-related measures in a model of inflammatory pain [11,12]. Although there is an increasing literature base on exercise-pain interactions [10,11,13,14], less is known about how the behavioral mechanism of wheel running acquisition duration (i.e., prior wheel running) affects the expression of chronic pain-like behavior.…”