Epigenetic remodeling induced by fatty acids: chromatin modifications and cellular senescence during lipid overload

Cellular senescence is a stable cell state sustained by specific gene expression programs that are established and maintained through dynamic changes in chromatin organization. Importantly, these programs are highly dependent on the nature of the senescence-inducing stimulus. In recent years, lipid overload has emerged as a relevant metabolic stress capable of inducing senescence across multiple cell types and tissues, particularly in the context of obesity and high-fat diets. Accumulating evidence indicates that this process is tightly linked to metabolic rewiring, which directly impacts chromatin-modifying enzymes and chromatin remodelers through fluctuations in key metabolites such as acetyl-CoA, NAD⁺, and α-ketoglutarate. In this review, we integrate current evidence on how fatty acid-driven metabolic alterations reshape chromatin dynamics to promote and stabilize cellular senescence. • Fatty acid-driven metabolic products reshape chromatin to foster cellular senescence • Histone PTMs integrate metabolic state with chromatin regulation • Chromatin remodelers link hyperlipidemia and senescence induction