Aging in the dermis: Fibroblast senescence and its significance

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence‐associated secretory phenotype (SASP). These events are regulated by signaling pathways, such as nuclear factor erythroid 2‐related factor 2 (Nrf2), mechanistic target of rapamycin (mTOR), transforming growth factor beta (TGF‐β), and insulin‐like growth factor 1 (IGF‐1). Senescent fibroblasts can induce and accelerate age‐related dysfunction of other skin cells and may even cause systemic inflammation. In this review, we summarize the role of dermal fibroblasts in cutaneous aging and inflammation. Moreover, the underlying mechanisms by which dermal fibroblasts influence cutaneous aging and inflammation are also discussed. This mini review discusses aging, inflammation, cellular senescence, and their orchestration in cutaneous aging, recognizing fibroblast senescence as central player and inflammation response as key mediator in these processes. We delve into the cascade effects of stress, senescence, SASP, and related signaling in fibroblasts, elucidating how they contribute to the amplification of inflammation and ultimately lead to the appearance and functional alterations observed in aged skin.