A recent study published in Nature Aging has identified a disturbance in branched-chain amino acid (BCAA) metabolism as a significant contributor to sarcopenia, opening the door to potential therapeutic interventions for muscle decline in aging. Sarcopenia, marked by a loss of muscle mass and function, is a leading cause of reduced physical capacity in older adults.
Sarcopenia leads to diminished muscle strength, increasing the risk of falls and injuries, with muscle mass typically decreasing by 15-30% each decade after the age of 50. Research has shown that metabolic dysfunction in skeletal muscle plays a critical role in sarcopenia development, further emphasizing the need to explore metabolic pathways to slow its progression.
The study highlights how impaired BCAA metabolism in muscles contributes to muscle atrophy. BCAAs, essential for muscle energy during exercise, accumulate in the muscles when their breakdown process is disrupted. This accumulation, along with its byproducts, interferes with muscle growth regulation, exacerbating muscle wasting. As a result, targeting BCAA metabolism could become a key strategy to delay sarcopenia’s onset.
The research involved 60 individuals aged 65 and older who required knee replacement surgery. The participants were categorized into three groups: healthy (HA), possible sarcopenia (PS), and obvious sarcopenia (S). Using advanced techniques like computed tomography and bioelectrical impedance, muscle mass and strength were assessed. The findings revealed that patients with sarcopenia showed significantly reduced muscle mass and strength, along with a notable decline in plasma albumin levels, compared to the healthy group.
Moreover, the study found suppressed expression of key genes involved in BCAA metabolism, particularly BCAT2 and BCKDHB enzymes. These enzymes are responsible for breaking down BCAAs. In sarcopenic patients, this genetic suppression led to BCAA buildup in muscles, disrupting normal muscle repair and growth mechanisms. In parallel, experiments on mice demonstrated similar metabolic disruptions, where impaired BCAA catabolism led to muscle atrophy and hindered recovery due to disturbed mTOR signaling pathways.
This study suggests that restoring proper BCAA metabolism could be an effective therapeutic strategy to combat sarcopenia. Enhancing BCAA catabolism in aging individuals may help preserve muscle mass and improve muscle function, thus improving their overall quality of life. The research marks an exciting step toward novel treatments to address sarcopenia and its debilitating effects in older populations.
