Lactate as an Exercise Mimetic: Mitigating Disuse Atrophy and Improving Muscle Endurance in Aging SAMP8 Mice

Lactate, historically considered a metabolic byproduct, has emerged as a key regulator of muscle physiology and metabolism. This study explores its potential as an exercise mimetic to counteract disuse muscle atrophy (DMA) in aging skeletal muscle using a hindlimb suspension model in senescence-accelerated prone 8 (SAMP8) mice. The mice were divided into four groups: Control, lactate-treated control, hindlimb suspension, and hindlimb suspension with lactate intervention. Lactate administration significantly preserved gastrocnemius muscle mass, restored muscle strength, and attenuated oxidative muscle fiber atrophy. Electrophoretic and histological analyses revealed an increase in MyHC I expression, indicating a protective effect on oxidative muscle fibers. Functional assessments showed that lactate improved muscle endurance and contractile force, while metabolomic profiling identified significant changes in energy metabolism, amino acid metabolism, and protein synthesis pathways. Specifically, lactate intervention improved impaired branched-chain amino acid metabolism, suggesting improved protein synthesis and recovery. In addition, lactate enhanced Cori cycle activity, upregulated hepatic lactate transporters, and increased lactate dehydrogenase B enzymatic activity, facilitating efficient lactate metabolism and gluconeogenesis. These results provide new insights into the role of lactate as a metabolic regulator and highlight its potential as a therapeutic intervention to combat exercise-induced muscle wasting and preserve muscle function in aging and immobilized individuals.