Unraveling the Epigenetic Landscape of Sarcopenic Obesity—Differential DNA Methylation in Older Women

Introduction and Objective: Sarcopenic obesity (SO) is a clinical condition characterized by the coexistence of obesity and sarcopenia, which is associated with adverse health outcomes in older adults. Despite its relevance, the epigenetic mechanisms underlying SO remain poorly understood. This study aimed to investigate DNA methylation profiles in older women with SO, obesity (Ob), sarcopenia (Sar), and healthy controls (H), with a focus on identifying differentially methylated pathways. Methods: This cross-sectional study included 32 older women (aged 60-75 years), categorized into four groups: SO, Ob, Sar, and H. Whole-blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip v2.0, alongside measurements of body composition (iDXA). Differentially methylated positions (DMPs) were identified using the ChAMP package, and pathway enrichment analysis was performed using ShinyGO 0.82. Results: Compared to the H group, the SO group exhibited 206 hypermethylated and 103 hypomethylated sites. The Ob group presented 117 hypermethylated and 134 hypomethylated sites, while the Sar group showed 104 hypermethylated and 81 hypomethylated sites. Enrichment analysis revealed significant pathways associated with SO, including Neutrophil Extracellular Trap formation, Systemic Lupus Erythematosus, Mucin-type O-glycan biosynthesis, and Alcohol metabolism. In the Ob group, hypomethylation was observed in pathways related to Selenocompound metabolism and African trypanosomiasis. Conclusion: Sarcopenic obesity is associated with distinct epigenetic modifications, particularly the hypermethylation of genes involved in inflammatory, autoimmune, and glycan metabolism pathways. In contrast, obesity was characterized by hypomethylation of genes related to selenium metabolism and immune response regulation. These findings highlight the complexity of epigenetic changes associated with aging and their potential implications for metabolic and immunological health. Disclosure: A.R. Venturini: None. C. Fogagnolo: None. G.D. Rodrigues: None. G.U. Ortiz: None. G.F. Abud: None. C.B. Nonino: None. A. Silva: None. E.C. Freitas: None. Funding: São Paulo Research Foundation (FAPESP), Brasil and National Council for Scientific and Technological Development (CNPq), process number: 2023/09554-0; 2023/01611-5.