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Regular endurance exercise of overloaded muscle of young and old male mice does not attenuate hypertrophy and improves fatigue resistance.

ABSTRACT: It has been observed that there is an inverse relationship between fiber size and oxidative capacity due to oxygen, ADP, and ATP diffusion limitations. We aimed to see if regular endurance exercise alongside a hypertrophic stimulus would lead to compromised adaptations to both, particularly in older animals. Here we investigated the effects of combining overload with regular endurance exercise in young (12 months) and old (26 months) male mice. The plantaris muscles of these mice were overloaded through denervation of synergists to induce hypertrophy and the mice ran on a treadmill for 30 min per day for 6 weeks. The hypertrophic response to overload was not blunted by endurance exercise, and the increase in fatigue resistance with endurance exercise was not reduced by overload. Old mice demonstrated less hypertrophy than young mice, which was associated with impaired angiogenesis and a reduction in specific tension. The data of this study suggest that combining endurance exercise and overload induces the benefits of both types of exercise without compromising adaptations to either. Additionally, the attenuated hypertrophic response to overload in old animals may be due to a diminished capacity for capillary growth.

SUBMITTER: Hendrickse PW

PROVIDER: S-EPMC8110681 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Regular endurance exercise of overloaded muscle of young and old male mice does not attenuate hypertrophy and improves fatigue resistance.

Hendrickse Paul William PW Krusnauskas Raulas R Hodson-Tole Emma E Venckunas Tomas T Degens Hans H

GeroScience 20200708 2

It has been observed that there is an inverse relationship between fiber size and oxidative capacity due to oxygen, ADP, and ATP diffusion limitations. We aimed to see if regular endurance exercise alongside a hypertrophic stimulus would lead to compromised adaptations to both, particularly in older animals. Here we investigated the effects of combining overload with regular endurance exercise in young (12 months) and old (26 months) male mice. The plantaris muscles of these mice were overloaded ...[more]

PMID: 32643063

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Project description:Aging is associated with vascular endothelial dysfunction, reduced exercise tolerance, and impaired whole-body glucose metabolism. Interleukin-37 (IL-37), an anti-inflammatory cytokine of the interleukin-1 family, exerts salutary physiological effects in young mice independent of its inflammation-suppressing properties. Here, we assess the efficacy of IL-37 treatment for improving physiological function in older age. Old mice (26-28 months) received daily intraperitoneal injections of recombinant human IL-37 (recIL-37; 1 µg/200 ml PBS) or vehicle (200 ml PBS) for 10-14 days. Vascular endothelial function (ex vivo carotid artery dilation to increasing doses of acetylcholine, ACh) was enhanced in recIL-37 vs. vehicle-treated mice via increased nitric oxide (NO) bioavailability (all p < .05); this effect was accompanied by enhanced ACh-stimulated NO production and reduced levels of reactive oxygen species in endothelial cells cultured with plasma from IL-37-treated animals (p < .05 vs. vehicle plasma). RecIL-37 treatment increased endurance exercise capacity by 2.4-fold, which was accompanied by a 2.9-fold increase in the phosphorylated AMP-activated kinase (AMPK) to AMPK ratio (i.e., AMPK activation) in quadriceps muscle. RecIL-37 treatment also improved whole-body insulin sensitivity and glucose tolerance (p < .05 vs. vehicle). Improvements in physiological function occurred without significant changes in plasma, aortic, and skeletal muscle pro-inflammatory proteins (under resting conditions), whereas pro-/anti-inflammatory IL-6 was greater in recIL-37-treated animals. Plasma metabolomics analysis revealed that recIL-37 treatment altered metabolites related to pathways involved in NO synthesis (e.g., increased L-arginine and citrulline/arginine ratio) and fatty acid metabolism (e.g., increased pantothenol and free fatty acids). Our findings provide experimental support for IL-37 therapy as a novel strategy to improve diverse physiological functions in old age.

Project description:The goal of the endurance exercise training study in young adult rats was to perform exercise training studies in young adult (6-month-old) F344 rats, and from these rats collect multiple tissues in order to provide high quality samples for detailed analysis by chemical analysis sites. Tissues were collected from 10-12 rats sedentary control rats concurrent with the collection of the 8-week training groups. The 8-week training group and controls were from the same cohort and same age at euthanasia. For the older age group, an additional set of controls (n=5-6) were collected with the 1-2 week training group. Rats were either sedentary or underwent an exercise training program. Rats were exercised on the rodent treadmill 5 days per week using a progressive training protocol designed to exercise the rats at approximately 70% of VO2max and training was performed no earlier than 10:00 am and no later than 5:00 pm over 5 consecutive days per week. Training was initiated with the treadmill set at 70% of VO2 max and 5 degrees grade for 20 minutes. The duration of exercise was increased by one minute each day until day 31 of training (start of week 7), when a duration of 50 min was reached. Speed and grade of each training session increased in larger increments due to treadmill parameters. The highest intensity and duration of training began on day 31. This intensity was maintained for the final 10 days of the protocol to ensure steady state had been achieved. If any rats were unable to perform at least 4 days of training per week they were removed from the study and euthanized. It is important to note that the starting treadmill speed varied depending on the sex and age of the rat. The initial and maximum speeds were based on VO2max measurements obtained during the pre-training testing of the compliant rats. Rats assigned to the control group followed a schedule similar to the training group. They were placed in one lane on the treadmill for 15 minutes/day, 5 days per week. The treadmill was set at 0 m/min at an incline that corresponded to the incline being used by the training group.

Project description:BackgroundInterventions to preserve functional capacities at advanced age are becoming increasingly important. So far, exercise provides the only means to counteract age-related decrements in physical performance and muscle function. Unfortunately, the effectiveness of exercise interventions in elderly populations is hampered by reduced acceptance and compliance as well as disuse complications. We therefore studied whether application of interleukin-6 (IL-6), a pleiotropic myokine that is induced by skeletal muscle activity and exerts broad systemic effects in response to exercise, affects physical performance and muscle function alone or in combination with training in aged mice.MethodsSedentary old male mice (Sed+Saline, n = 15) were compared with animals that received recombinant IL-6 (rIL-6) in an exercise-mimicking pulsatile manner (Sed+IL-6, n = 16), were trained with a moderate-intensity, low-volume endurance exercise regimen (Ex+Saline, n = 13), or were exposed to a combination of these two interventions (Ex+IL-6, n = 16) for 12 weeks. Before and at the end of the intervention, mice underwent a battery of tests to quantify endurance performance, muscle contractility in situ, motor coordination, and gait and metabolic parameters.ResultsMice exposed to enhanced levels of IL-6 during endurance exercise bouts showed superior improvements in endurance performance (33% more work and 12% greater peak power compared with baseline), fatigue resistance in situ (P = 0.0014 vs. Sed+Saline; P = 0.0199 vs. Sed+IL-6; and P = 0.0342 vs. Ex+Saline), motor coordination (rotarod performance, P = 0.0428), and gait (gait speed, P = 0.0053) following training. Pulsatile rIL-6 treatment in sedentary mice had only marginal effects on glucose tolerance and some gait parameters. No increase in adverse events or mortality related to rIL-6 treatment was observed.ConclusionsAdministration of rIL-6 paired with treadmill running bouts potentiates the adaptive response to a moderate-intensity low-volume endurance exercise regimen in old mice, while being safe and well tolerated.

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Regular endurance exercise of overloaded muscle of young and old male mice does not attenuate hypertrophy and improves fatigue resistance.

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Regular endurance exercise of overloaded muscle of young and old male mice does not attenuate hypertrophy and improves fatigue resistance.

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