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Lynch, Magnus D.

A5112977410 | I1298207432

Mayo Clinic

Guy's Hospital

Citations 2

Regenerative Medicine: On the Vanguard of Dermatology

Dermatologic Surgery | October 31, 2024 | Volume: 50 | Issue: 11S | Pages: S128-S130

10.1097/dss.0000000000004388 | PMID 39480033

Mapping epidermal and dermal cellular senescence in human skin aging

Aging Cell | October 7, 2024 | Volume: 24 | Issue: 1 | Pages: No page available

10.1111/acel.14358 | PMID 39370688

Abstract 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 ‐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 + (p21) 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.