Ageing rewires visceral adipocyte identity and lipid metabolism through coordinated epigenomic and transcriptomic remodelling

Notably, ageing-DMRs located near ageing-DEGs displayed higher CpG and GC content, active chromatin features, and enrichment for motifs of ageing-relevant transcription factors compared with ageing-DMRs as a whole. Targeted lipidomic analysis of adipocytes revealed pronounced, cell-intrinsic remodelling of the lipidome, including selective depletion of triglycerides and accumulation of ceramides, largely uncoupled from systemic lipid changes.

Integration of lipidomic and transcriptomic data highlighted coordinated downregulation of glycerolipid biosynthesis and lipolysis genes alongside upregulation of sphingolipid and ceramide metabolism pathways, frequently accompanied by ageing-associated DNA methylation changes. Collectively, our findings demonstrate that ageing drives coordinated epigenetic, transcriptional, and metabolic rewiring across visceral adipose cell types, linking loss of cellular identity and ceramide accumulation to intrinsic adipose ageing and metabolic dysfunction