Combined exercise-induced modulation of Notch pathway and muscle quality in senescence-accelerated mice.

Ana P Pinto, Ângelo Augusto J Sarni, Maria Eduarda A Tavares, Alisson L da Rocha, Ruither O Gomes Carolino, Ivo V de Sousa Neto, Driele C Da Silva Ferreira, Vitor R Munoz, Giovana R Teixeira, Fernando M Simabuco, José R Pauli, Dennys E Cintra, Eduardo R Ropelle, Ellen C de Freitas, Adelino S R da Silva

School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14040-907, Brazil.School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14040-907, Brazil. · pubmed

Paper

Abstract

The Notch signaling pathway is crucial for skeletal muscle development, regeneration, inflammation, and aging. This study investigated the association between interleukin-10 (IL-10) and the Notch pathway in C2C12 cells, as well as explored the effects of combined endurance and resistance exercise on the Notch and autophagy pathways in the skeletal muscle of senescence-accelerated mouse-resistant 1 Sedentary (SAMR1 CT), SAMR1 exercised (SAMR1 EX), senescence-accelerated prone mouse 8 Sedentary (SAMP8 CT), and SAMP8 exercised (SAMP8 EX). C2C12 myoblasts were transfected with siIL-10. Histological analysis, reverse transcription-quantitative polymerase chain reaction, and immunoblotting were performed on the quadriceps and tibialis anterior muscles. A publicly available dataset was analyzed to assess the Notch pathway in older men. In summary, IL-10 knockdown in myoblasts reduced the Notch pathway gene and protein expression. In SAMP8 mice, combined exercise improved muscle fiber organization, enhanced balance and coordination, and increased Notch2 and Hes1 mRNA levels. NOTCH2 mRNA levels were also higher in older men compared to young subjects with similar physical activity levels. These findings suggest that combined physical exercise enhances muscle regeneration via the Notch pathway in aged muscle.

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Research summary

The paper investigates the role of the Notch signaling pathway in muscle regeneration and aging, which is pertinent to understanding mechanisms of aging and potential interventions. While it provides solid research on the effects of combined exercise on muscle quality in aged mice, the findings are somewhat incremental and do not present a groundbreaking advance in the field of longevity research. The study contributes to the understanding of exercise's role in muscle health during aging but lacks broader implications for lifespan extension or addressing root causes of aging.

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