Renin angiotensin system-induced muscle wasting: putative mechanisms and implications for clinicians

Area of Science:

• Physiology
• Molecular Biology
• Gerontology

Background:

• The Renin Angiotensin System (RAS) plays a critical role in regulating physiological processes.
• Dysregulation of the RAS is implicated in various pathological conditions, including muscle wasting and sarcopenia.
• The RAS comprises distinct classical and non-classical pathways with opposing effects on skeletal muscle.

Purpose of the Study:

• To review the multifaceted mechanisms by which the classical and non-classical RAS pathways influence muscle wasting.
• To explore the potential clinical implications of targeting the RAS for sarcopenia treatment.
• To identify knowledge gaps and suggest future research directions in RAS-mediated muscle atrophy.

Main Methods:

• Literature review of studies investigating the Renin Angiotensin System and its components.
• Analysis of molecular and cellular mechanisms underlying RAS-induced muscle wasting.
• Synthesis of evidence regarding the protective role of the non-classical RAS pathway.

Main Results:

• The classical RAS pathway, mediated by Angiotensin II (AngII) and AT1 receptors, promotes muscle wasting through reduced food intake, increased proteolysis, apoptosis, inflammation, oxidative stress, and impaired mitochondrial function.
• The non-classical RAS pathway, involving Angiotensin 1-7 and the Mas receptor, counteracts these catabolic effects, offering protection against sarcopenia.
• Specific molecular targets include orexin, neuropeptide Y, IGF-1, mTOR, FOXO, caspase, TNF-α, and IL-6.

Conclusions:

• The balance between classical and non-classical RAS pathways is crucial for maintaining skeletal muscle mass and function.
• Targeting specific components of the RAS presents a promising therapeutic strategy for combating muscle wasting and sarcopenia.
• Further research is needed to fully elucidate the complex interactions within the RAS and its clinical applications.