Transcriptomic Signatures of Sarcopenia Reversal Through High Leucine Protein Supplementation in Frailty

Abstract

Sarcopenia is one of the main reasons for the elderly to become weak. There is an age-related loss of muscle mass, muscle strength, and performance, which results in more disability, falls, and health services. Although high-leucine protein supplementation has proved promising in alleviating sarcopenia, its underlying mechanism, especially in frail patients, is under-researched. The purpose of this study is to investigate the impact of high-leucine protein supplement on muscle mass, muscle strength, physical functioning, and gene expression in frail older adults. It is an 80-participant, randomized, placebo-controlled, and blinded clinical trial based on age (65 years and above). These participants were selected to be randomized into a high-leucine protein supplement (50 g of protein, 6g of leucine/day) and a placebo (12 weeks). RNA sequencing is used to analyse gene expression, and functional results were evaluated by measuring muscle mass, handgrip strength, and the Short Physical Performance Battery (SPPB). This intervention group showed a statistically significant (p < 0.05) 3.2% increment in muscle mass, 12.5% improvement in handgrip strength, and a 2.1-point improvement in SPPB score, over 12 weeks, compared with the placebo group, which did not change. Analysis of gene expression showed upregulation of mTOR, S6K1, PGC1α, and NRF1, which participate in muscle protein synthesis and mitochondrial biogenesis, and downregulation of TNF-α and IL-6, which indicates a decrease in inflammation. This paper gives good evidence to prove that leucine supplementation can enhance muscle functionality and reverse sarcopenia in frail individuals by regulating main molecular pathways, which is why this has the potential to become a therapeutic tool in the treatment of frailty.Sarcopenia, frailty, leucine supplementation, muscle mass, gene expression, inflammation, physical function