Beta-alanine-carnosine buffering and glutamine metabolism synergistically enhance muscle-brain axis resilience in aging.

Aging is characterized by progressive declines in muscular performance, cognitive abilities, and metabolic flexibility, all interconnected via the muscle-brain axis. Current interventions often fall short in comprehensively addressing these multifaceted deteriorations. This review explores how specific amino acids, beta-alanine (BA) and glutamine, may not act in isolation but rather converge mechanistically to modulate this axis, offering a novel, integrated approach to bolster resilience against age-related decline and neurodegeneration.

This review systematically consolidates existing literature on beta-alanine (BA) and glutamine, focusing on their mechanistic interplay within the muscle-brain axis. It synthesizes evidence regarding their roles in intracellular pH regulation via carnosine biosynthesis, nitrogen metabolism, and redox equilibrium. The authors examined how these amino acids collectively influence mitochondrial function, neuroplasticity, and neuroinflammation, particularly in the context of exercise, aging, and neurodegenerative disorders, to propose a unified mechanistic paradigm.

The review highlights that beta-alanine, through its conversion to carnosine, significantly augments intracellular buffering capacity, maintaining pH stability during metabolic stress scenarios like exercise and age-related mitochondrial dysfunction. This pH regulation is critical for glutamine metabolism, safeguarding pH-sensitive enzymes such as glutamine synthetase and glutaminase, thereby preserving glutamine turnover and nitrogen flux in acidic environments. > Glutamine operates as a pivotal metabolic substrate, connecting skeletal muscle and the brain by facilitating energy homeostasis, immune modulation, antioxidant protection, and neurotransmitter recycling through the glutamate-glutamine axis. These synergistic actions collectively enhance mitochondrial functionality, neuroplasticity, and mitigate neuroinflammation, with physical exercise further intensifying these beneficial interactions.