Contribution of lipids and epilipids to the hallmarks of skin aging

Mammalian aging is characterized by progressive alterations in cellular metabolism, loss of macromolecular homeostasis of nucleic acids and proteins, heightened redox stress, and chronic low-grade inflammation. Among the established hallmarks of aging, changes in lipid synthesis, -utilization, and -modification have emerged as particularly significant contributors. In the skin, age-associated remodeling of the lipidome is detectable across its distinct anatomical compartments and at the level of individual cell types. Beyond chronological aging, which proceeds systemically across all tissues, the skin is uniquely subject to photoaging - an extrinsically driven process that induces a characteristic senescent phenotype in chronically sun-exposed regions. Both intrinsic and extrinsic aging mechanisms are accompanied by shifts in the cutaneous lipidome, comprising alterations in lipid class composition as well as oxidative and other chemical modifications. The totality of such chemically modified lipids is captured by the concept of the epilipidome. Lipids and epilipids are increasingly recognized not only as biomarkers of age-related damage, but also as active biological mediators shaping the aging skin's cellular and tissue biology. Building on the recently updated framework of the "hallmarks of aging" proposed by López-Otín and colleagues, this review systematically maps the contributions of lipids and the epilipidome to the molecular and cellular processes underlying skin aging.