A new study published in Nature Aging identifies disrupted branched-chain amino acid (BCAA) metabolism as a key driver of sarcopenia, a condition characterized by progressive muscle loss and weakness. Researchers used multi-omics analysis to compare muscle tissue from individuals with sarcopenia, those with possible sarcopenia, and healthy older adults. Their findings highlight BCAA catabolism as a potential therapeutic target for slowing muscle deterioration and improving aging health.
By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Feb 17 2025 New research pinpoints faulty branched-chain amino acid metabolism as a driving force behind sarcopenia, highlighting a potential pathway to slow muscle deterioration and improve aging health.
Study: Multi-omic Profiling of Sarcopenia Identifies Disrupted Branched-chain Amino Acid Catabolism As a Causal Mechanism and Therapeutic Target. Image Credit: Kurteev Gennadii / Shutterstock.com A recent Nature Aging study uses multi-omics to identify the molecular and metabolic signatures of skeletal muscle in patients with sarcopenia. How does aging affect muscles? Skeletal muscle constitutes approximately 40% of total body mass. Typically, muscle mass and strength peak during young adulthood and decline by 15-30% each decade after 50 years of age. Sarcopenia is a condition characterized by progressive deterioration in muscle mass and function, which leads to functional loss, frailty, and increased mortality in older adults. Previous studies have revealed that sarcopenia is caused by inflammation, impaired protein synthesis, physical inactivity, endocrine changes, insulin resistance, and mitochondrial dysfunction. Sarcopenia is associated with pathological alterations in metabolic dysregulation in skeletal muscles. This dysregulation affects protein and glycogen synthesis and degradation. Sarcopenia also impacts energy utilization, leading to structural and functional dysfunction of skeletal muscle. Despite these observations and the high prevalence of sarcopenia among older adults, no treatment is currently approved to treat this condition. What is BCAA? Branched-chain amino acids , which are primarily metabolized in skeletal muscle, are a key energy source during physical activities. Previous in vivo studies in mice have revealed that BCAA supplementation can improve muscle mitochondrial biogenesis, leading to greater muscle strength and mass; however, some studies have reported contradictory findings. About the study The current study integrated transcriptomic, metabolomic, and proteomic data to determine the molecular and metabolic signatures of skeletal muscle in patients with sarcopenia. Vastus lateralis muscle specimens were collected from the West China Hospital of Sichuan University between July 1, 2021. and October 31, 2023. Individuals over 65 who were recommended for knee arthroplasty, with no history of fracture, trauma, or neuromuscular diseases, were invited to participate in the study. All participants could walk independently. The analysis excluded individuals with a history of musculoskeletal disorders, cardiovascular conditions, and metabolic diseases. To validate the findings of the multi-omics analysis, a replication cohort consisting of 40 age-matched and sex-matched individuals was used. Study findings Out of 250 individuals screened for knee surgery, 60 age- and sex-matched individuals were selected for multi-omics analysis. Among these participants, 20 were diagnosed with sarcopenia , 20 with possible sarcopenia , and 20 healthy-aged controls. S and PS were identified based on the skeletal muscle index measured from computed tomography scans, bioelectrical impedance analysis , grip strength, and gait speed. Individuals with PS exhibited low muscle function with normal muscle mass, whereas those diagnosed with S exhibited poor muscle strength and mass. Compared to HA, individuals at the S stage exhibited a significant reduction in plasma albumin levels. Body mass index , SMI of the third lumbar vertebra, upper arm circumference, and calf circumference were also significantly lower in S individuals than in HA and PS study participants. Grip strength and gait speed gradually reduced with an increase in the frailty index across the three stages. Sarcopenia progression was inversely associated with SMI, muscle mass, and muscle strength. Using high-coverage ribonucleic acid sequencing of vastus lateralis muscle samples, 453 differentially expressed genes were identified among HA, PS, and S participants. Further investigation revealed that S participants were transcriptionally distinct from both the HA and PS groups. Most DEGs exhibited a linear correlation with disease trajectory. Although principal component analysis and Euclidean distance analyses indicated similar transcriptional profiles of the HA and PS groups, the S samples exhibited distinct metabolic gene expression patterns. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference in metabolic pathways between HA and S samples, including oxidative phosphorylation, glycolysis, fatty acid metabolism, BCAA catabolism, the tricarboxylic acid cycle, pyruvate metabolism. Most genes involved in these metabolic pathways were downregulated during sarcopenia progression. For example, the expression of branched-chain amino acid transaminase 2 and BCKDHB genes, which are responsible for the synthesis of enzymes involved in BCAA catabolism, were significantly decreased in the skeletal muscle of patients with sarcopenia. This genetic inhibition led to a significant accumulation of BCAAs and BCKAs. A skeletal muscle-specific Ppm1k knockout mouse model was used to examine the effects of disrupted BCAA catabolism on sarcopenia. The model revealed that impaired BCAA catabolism influences muscle and adipose pathology in mice. Moreover, impaired BCAA catabolism led to BCAA accumulation and sustained mechanistic target of rapamycin activation, thereby leading to dysregulated mTOR signaling, which causes skeletal muscle atrophy. Conclusions The current study identified BCAA catabolic dysfunction and accumulation as key metabolic defects present in early-stage sarcopenia. These findings indicate that increasing BCAA catabolism could mitigate the progression of sarcopenia.
SARCOPENIA MUSCLE LOSS Bcaas METABOLISM AGING
United Kingdom Latest News, United Kingdom Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Sewage Nightmare: Homeowners Live in 'Frightening' Conditions on Faulty New-Build EstateHomeowners on a new-build estate in Penenden Heath are suffering from a sewage nightmare, with toilets unusable and raw sewage flooding the streets. The residents have spent over £50,000 on repairs and emergency sewage removals since December 2023 due to a faulty sewage pump system. Despite paying for waste removal services, responsibility for the maintenance of the sewage station has fallen to them, leaving them trapped in a desperate situation.
Read more »
Garmin Smartwatches Hit by 'Blue Triangle of Death' After Faulty UpdateGarmin users are facing a frustrating issue after a recent update bricked many smartwatches, displaying a blue triangle of death. The faulty update appears to have been caused by a corrupted file distributed by Garmin, which has since been pulled. However, some smartwatches may have already downloaded the problematic file, rendering them unusable. Users are seeking solutions and compensation from Garmin, while social media is buzzing with disappointment over the company's handling of the situation.
Read more »
Study: Sleep Patterns Linked to Heart Health, Metabolism, and MoreA recent study published in Nature Medicine analyzed sleep data from thousands of individuals and found that sleep traits were stronger predictors of health markers than age, BMI, or even visceral adipose tissue. The research highlights the importance of sleep for overall health and reveals connections between sleep and cardiovascular health, metabolism, mental well-being, and more.
Read more »
Gut Bacteria's Sugar Compounds Influence Metabolism, Control Blood Sugar, and Reduce FatA new study published in Nature Communications reveals how sugar-derived compounds produced by gut bacteria influence metabolism, helping to control blood sugar levels, reduce fat accumulation, and potentially pave the way for new probiotic therapies.
Read more »
New Microscopy Technique Reveals Insights into Cancer Cell Metabolism and Treatment ResistanceResearchers at the University of Kentucky have developed a novel microscopy technique that uses standard fluorescence microscopes to analyze metabolic changes in individual cancer cells. This approach provides a cost-effective and accessible way to study how tumors adapt to therapies and develop resistance.
Read more »
Urgent warning that boiler mistake ‘could fill your home with deadly gas’Skipping professional inspections increases the risk of carbon monoxide leaks, faulty ventilation, and even gas explosions.
Read more »