ALDH1A3, CSF1R, and PHGDH serve as potential co-morbid biomarkers for sarcopenic obesity, identified through machine learning integration of differentially expressed genes and gut microbiota metabolite targets, and validated in mouse models and independent cohorts.
The incidence of sarcopenic obesity in China increased significantly from 16.1% in 2011 to 20.4% in 2018.
Machine learning methods identified ALDH1A3, CSF1R, and PHGDH as key co-morbid biomarker genes for sarcopenic obesity.
The three key genes demonstrated robust diagnostic performance with AUC values exceeding 0.72 across four independent GEO cohorts.
ALDH1A3 and CSF1R expression in muscle tissue was significantly upregulated in a high-fat-diet induced mouse model, while PHGDH showed a consistent upward trend that did not reach statistical significance.
Immune infiltration analysis revealed a significant increase in resting NK cells in both obesity and sarcopenia states.
Functional enrichment analyses linked ALDH1A3, CSF1R, and PHGDH to transcriptional regulation pathways.
Molecular docking simulations indicated stable binding of the candidate therapeutic compound Birinapant to the key gene targets.
Gut microbiota metabolite targets were integrated with transcriptomic data to identify sarcopenic obesity-relevant genes.
This research suggests that sarcopenic obesity — a condition where a person has both excess body fat and reduced muscle mass — is becoming increasingly common among older adults in China, rising from about 16% to over 20% between 2011 and 2018. To better understand the biological mechanisms behind this condition, the researchers combined multiple computational approaches including machine learning and gene network analysis, and also incorporated information about gut bacteria and the chemical compounds they produce. This led to the identification of three genes — ALDH1A3, CSF1R, and PHGDH — as potential shared biomarkers for sarcopenic obesity, meaning these genes may play important roles in both the fat and muscle components of the condition simultaneously. The researchers validated these three genes using multiple independent datasets and a mouse model in which obesity was induced through a high-fat diet. In the mouse model, two of the three genes (ALDH1A3 and CSF1R) were significantly more active in muscle tissue, supporting their relevance to the disease. Additionally, the researchers found that a specific type of immune cell called resting NK cells was elevated in both obesity and sarcopenia, suggesting the immune system plays a role in this condition. The genes were also connected to fundamental cellular processes including autophagy (cellular recycling) and ferroptosis (a form of cell death). This research suggests that these three genes could potentially serve as diagnostic markers to identify individuals with or at risk for sarcopenic obesity, and that a drug called Birinapant may be worth investigating as a potential treatment based on its predicted ability to interact with these gene targets. These findings may help guide future research into earlier diagnosis and targeted therapies for a condition that significantly reduces quality of life in older adults, though further clinical studies would be needed to confirm these possibilities.
Wang J, Li H, Shi W, Ren X, Liu Y, Mao L, et al.. (2026). Co-morbid biomarkers for sarcopenic obesity associated with gut microbiota metabolites: From burden to treatment.. PLoS computational biology. https://doi.org/10.1371/journal.pcbi.1014225