Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice

Abstract

This study compared the capacity of young and old male C57Bl/6J mice to exercise with increasing resistance over 10 weeks, and its impact on muscle mass. Young mice (aged 15-25 weeks) were subjected to low (LR) and high (HR) resistance exercise, whereas only LR was used for old mice (107-117 weeks). Weekly patterns of voluntary wheel activity, food consumption and body weights were measured. Running patterns changed over time and with age, with two peaks of activity detected for young, but only one for old mice: speed and distance run was also less for old mice. The mass for six limb muscles was measured at the end of the experiment. The most pronounced increase in mass in response to exercise was for the soleus in young and old mice, and also quadriceps and gastrocnemius in young mice. Soleus and quadriceps muscles were analyzed histologically for myofiber number and size. A striking feature was the many small myofibers in response to exercise in young (but not old) soleus, whereas these were not present after exercise in young or old quadriceps. Overall, there was a striking difference in response to exercise between muscles and this was influenced by age.

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

“…Mice in the present study had typical circadian running patterns, characterized by two peaks of activity: one 2–3 h prior to lights on and another 2–3 h prior to lights out, which is a characteristic of young, rather than old C57BL/6J mice where activity is defined by only one main peak of activity [24]. Given the voluntary nature of wheel running, distances run by mice in the present study were inversely proportional to the wheel load and decreased from an average of 4.6 and 5.9 km per day for males and females, respectively, on an unloaded wheel, to an average of 2 and 1.4 km per day at 6 g resistance (W21–34).…”

“…Given the voluntary nature of wheel running, distances run by mice in the present study were inversely proportional to the wheel load and decreased from an average of 4.6 and 5.9 km per day for males and females, respectively, on an unloaded wheel, to an average of 2 and 1.4 km per day at 6 g resistance (W21–34). While C57BL/6J mice are less avid wheel runners than other strains [51], we have previously shown that male C57BL/6J mice (aged ~25–27 months) are capable of running approximately 3 km per night on an unloaded wheel and 0.5 km with 4 g of resistance [24]. …”

“…The Activity Wheel Monitoring (AWM) software (Model 86065) was used to record all datasets. Wheel loading was determined by hanging known weights on each individual wheel and adjusting the brake to hold each selected weight as per manufacturer’s instructions [24]. These wheels were generously made available to us through an extended collaboration with Murray Goulburn Co-operative Co. Limited, Australia.…”

“…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]. …”

“…We have previously shown in mice that short-term voluntary wheel running (10 weeks) combined with resistance is sufficient to induce hindlimb muscle hypertrophy in the quadriceps, gastrocnemius, and soleus (by up to 52%) of young male C57BL/6J mice (aged 16 weeks), and in the soleus (18%) of very old, sarcopenic mice (27 months) [24]. Little is known about the long-term adaptive molecular responses of the aging mouse skeletal muscle to voluntary resistance exercise and, in particular, whether this may differ between males and females.…”