Effects of combined physical exercise on Notch and autophagy pathways in skeletal muscle in early aging animal model

• Grant number: 22/01957-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2022
• End date: July 31, 2023
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Ângelo Augusto Junqueira Sarni
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia, AP.TEM

Abstract

During aging, there is a loss of muscle mass and strength, also known as sarcopenia. Furthermore, skeletal muscles are constantly challenged with a multitude of mechanical, thermal, and oxidative stresses, which can result in cell damage and death. Two pathways affected by aging are the Notch and autophagy pathways. Notch signaling aids in muscle development, as well as proliferation and cell fate determination of muscle-specific satellite cells during myogenesis. Autophagy maintains skeletal muscle homeostasis by recycling damaged proteins and organelles. Physical exercise helps in the prevention of sarcopenia, as well as in the increase of the autophagic process that is diminished in aging. Knowing the relationship between aging and Notch and autophagy signaling pathways, the present project will verify the effects of combined physical exercise on Notch and autophagy pathways in the skeletal muscle of mice with premature aging. 10 male mice SAMP8 (senescence-accelerated prone mouse 8) aged 7 months and 10 male mice SAMR1 (senescence-accelerated mouse-resistant 1) aged 7 months will be used as a control strain, divided into sedentary and combined exercise groups. The combined exercise protocol will consist of 3 days of treadmill running and 2 days of stair climbing over 3 weeks. The animals will be submitted to the glucose tolerance test, the rotarod test, the grip strength test, and the incremental load test. Subsequently, the tibialis anterior (TA) skeletal muscle will be removed and frozen at -80º C for real-time polymerase chain reaction (qRT-PCR) and immunoblotting analyses.(AU)