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Effects of improved unfolded protein response induced by endurance exercise or heat stress in physically inactive aged male rats

In: Comparative Exercise Physiology
Authors:
W. Isobe Course in Physical Therapy, Graduate School of Health Sciences, Kyoto Tachibana University, 34 Oyakeyamada, Yamashina Ward, Kyoto City, Kyoto 607-8175, Japan
Department of Rehabilitation, Mitsubishi Kyoto Hospital, 1 Katsuragosho, Nishikyo Ward, Kyoto City, Kyoto 615-8087, Japan

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https://orcid.org/0000-0002-6009-9634
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S. Murakami Department of Physical Therapy, Faculty of Health Care Sciences, Himeji-Dokkyo University, 7-2-1 Kamiono, Himeji City, Hyogo 670-0896, Japan

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https://orcid.org/0009-0002-1186-8836
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K. Nonaka Department of Rehabilitation, Faculty of Health Sciences, Naragakuen University, 15-1 Nakatomigaoka 3-chome, Nara City, Nara 631-8524, Japan

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https://orcid.org/0000-0002-7176-9656
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R. Miyachi Department of Physical Therapy, Hokuriku University, 1-1 Taiyogaoaka 1-chome, Kanazawa City, Ishikawa 920-1180, Japan

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https://orcid.org/0000-0002-4890-4223
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M. Sakita Graduate School of Health Sciences, Kyoto Tachibana University, 34 Oyakeyamada, Yamashina Ward, Kyoto City, Kyoto 607-8175, Japan

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https://orcid.org/0000-0001-5765-760X
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Abstract

Skeletal muscles exhibit an increase in unfolded protein response (UPR) with ageing, but prolonged endoplasmic reticulum stress can impair UPR function, contributing to sarcopenia. While exercise and heat stress have been shown to activate the UPR in young rats, it remains unclear whether similar effects occur in physically inactive aged rats. Based on prior findings, we hypothesised that endurance exercise and heat stress would each activate the UPR in aged rats, with endurance exercise having a stronger effect. Here, we aimed to investigate changes in UPR-related protein expression and the differential responses to endurance exercise or heat stress over four weeks in physically inactive aged male rats. At 95 weeks of age, 18 male Wistar rats were randomly assigned to control (Co), endurance exercise (Ex), or heat stress (HE) groups (n = 6 each). The Ex group performed treadmill running (10 m/min, 0° incline, 60 min/session), whereas the HE group underwent whole-body heat stress (42 °C, 70 min/session), 3-4 times per week for 4 weeks. Following the intervention period, the soleus muscle was analysed. The Ex group showed a marked increase in UPR marker expression and a marked decrease in apoptosis-promoting factors compared to the Co group. No significant changes in UPR markers were observed in the HE group. A decrease in apoptosis-promoting factors suggests that endurance exercise may suppress skeletal muscle apoptosis. Moreover, since heat stress did not alter UPR-related protein expression, we interpreted that any heat stress-induced changes may have returned to baseline at an early stage. Overall, our findings may provide supporting evidence for the potential effectiveness of endurance exercise interventions in physically inactive older adults, while further studies are needed to explore heat stress as a non-exercise intervention.

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