The role of interleukin-10 in mitigating endoplasmic reticulum stress in aged mice through exercise

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Marafon, Bruno Brieda ; Pinto, Ana Paula ; de Sousa Neto, Ivo Vieira ; da Luz, Caroline Mantovani ; Pauli, Jose Rodrigo ; Cintra, Dennys Esper ; Ropelle, Eduardo Rochete ; Simabuco, Fernando Moreira ; de Moura, Leandro Pereira ; de Freitas, Ellen Cristini ; Rivas, Donato Americo ; da Silva, Adelino Sanchez Ramos

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 327, n. 3, p. 12-pg., 2024-09-01.

Resumo

Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2 alpha/eIF2 alpha). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2 alpha/eIF2 alpha protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle. (AU)

• Processo FAPESP: 21/06291-3 - EMU concedido no processo 2019/11820-5: ChemiDoc Imaging System e acessórios
• Beneficiário: Adelino Sanchez Ramos da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 21/08693-1 - Efeito da deleção global ou condicional (músculo esquelético) do gene Nr1d1 sobre o envelhecimento
• Beneficiário: Ana Paula Pinto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/14233-3 - Efeitos da deleção condicional do PGC-1alfa e exercício físico sobre as vias de biogênese mitocondrial, autofagia e rev-erb-alfa no músculo esquelético de camundongos: uma abordagem proteômica
• Beneficiário: Ivo Vieira de Sousa Neto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/11820-5 - Função do Nr1d1 sobre a Sarcopenia associada ao envelhecimento
• Beneficiário: Adelino Sanchez Ramos da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 22/09100-7 - Papel da rev-erb-alfa no estresse do retículo endoplasmático associado ao envelhecimento
• Beneficiário: Bruno Brieda Marafon
• Modalidade de apoio: Bolsas no Brasil - Doutorado