Characterizing Senescent Cell Burden in Skin

Researchers here work towards developing a better characterization of the age-related burden of senescent cells in skin tissue. As for all tissues in the body, the number of senescent cells in skin grows with age. This is the result of an imbalance between pace of creation and pace of clearance by the immune system; with age, cell stress increases while the capabilities of the immune system decline. Lingering senescent cells constantly secrete pro-inflammatory signals, and this contributes to body-wide inflammation. Skin is a large organ, and provides a meaningful fraction of this contribution of senescent cells to the whole body chronic inflammation of aging.

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and cell-extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging.

A skin-specific cellular senescence gene set, termed SenSkin, was curated and confirmed to be elevated in the context of photoaging, chronological aging, and non-replicating CDKN1A+ cells. In the epidermis, senescent melanocytes were associated with elevated melanin synthesis, suggesting haphazard pigmentation, while in the dermis, senescent reticular dermal fibroblasts were associated with decreased collagen and elastic fiber synthesis. Spatial analysis revealed the tendency for senescent cells to cluster, particularly in photoaged skin. This work proposes a strategy for characterizing age-related skin dysfunction through the lens of cellular senescence and suggests a role for senescent epidermal cells (i.e., melanocytes) and senescent dermal cells (i.e., reticular dermal fibroblasts) in age-related skin sequelae.