Functional and molecular mechanisms involved in the actions of the bile acid TUDCA in skeletal muscle in the face of aging

Author(s)

Marina dos Santos Carvalho

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2024-03-14

Examining board members

Helena Cristina de Lima Barbosa; Laís Rosa Viana; Jean Franciesco Vettorazzi

• Advisor: Helena Cristina de Lima Barbosa

Abstract

According to the World Health Organization, the world population over the age of 60 is expected to double by 2050, reaching almost 2 billion. In addition to the greater propensity for the emergence of cardiovascular diseases, cancer, neurodegenerative diseases, and type II diabetes mellitus, aging is also related to changes in body composition and morphology, such as an increase in adipose tissue and a decrease in skeletal muscle mass. In elderly individuals, the loss of muscle mass associated with the loss of function (sarcopenia) is related to several factors such as decreased absorption of nutrients, chronic inflammation in various tissues, and decline in the signaling of hormones, such as insulin, which reflect in greater activation of proteolysis pathways and decreased activation of protein synthesis pathways in muscle. Thus, sarcopenia decreases the individual's mobility and increases the propensity for the development or worsening of metabolic diseases, such as diabetes and obesity. For the treatment of chronic diseases related to aging, bile acids have shown to be effective, among them, tauroursodeoxycholic bile acid (TUDCA) stands out for presenting a broad systemic action and low toxicity in humans. TUDCA is capable of reducing reticulum stress in several cell types, attenuating damage caused by type I and II diabetes mellitus, attenuating metabolic dysfunctions resulting from aging, in addition to increasing insulin sensitivity in peripheral tissues. In skeletal muscle tissue, studies also show that TUDCA is capable of attenuating muscle atrophy in animals subjected to treatment with dexamethasone, compensating for the harmful effects this drug causes on the tissue. However, little is known about the mechanisms triggered in the muscle resulting from the administration of this bile acid in the senile organism. In this work, we used senile C57BL/6 mice, 18 months old, treated with TUDCA at 300mg/kg (Old+TUDCA), or PBS (Old) intraperitoneally; we aimed to evaluate the actions of this bile acid as a possible modulator of protein degradation and synthesis pathways to attenuate sarcopenia. Our results show that senile animals treated with TUDCA had increased gastrocnemius, soleus, tibialis anterior (TA), and extensor digitorum longus (EDL) muscle mass and better performance during muscle strength tests, in addition to a decrease in total body weight when compared to animals in the Old group. It was possible to observe a modulation in the expression and phosphorylation of proteins that are important for controlling protein synthesis signaling in muscle as well. TUDCA was also able to reduce inflammation in the skeletal muscle of Old animals, normalize plasma levels of FGFs 15 and 21, IGF-1, and myostatin, and restore the size of muscle fibers, preserving the architecture and tissue function. Our results indicate that TUDCA can mitigate the effects caused by aging, such as loss of muscle mass and strength. Thus, this work contributes to a better understanding of the actions of TUDCA on the skeletal muscles of senile individuals, being a promising alternative for the attenuation of sarcopenia related to aging process (AU)

• FAPESP's process: 21/13917-6 - Functional and molecular mechanisms involved in the actions of bile acid TUDCA in skeletal musculature in the face of aging
• Grantee: Marina dos Santos Carvalho
• Support Opportunities: Scholarships in Brazil - Master