Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

1-1-2025

Journal

Aging Cell

DOI

10.1111/acel.14358

PMID

39370688

PMCID

PMC11709101

PubMedCentral® Posted Date

10-6-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Skin Aging, Cellular Senescence, Epidermis, Dermis, Fibroblasts, Melanocytes, Adult, Ultraviolet Rays, cellular senescence, dermis, epidermis, single‐cell gene expression analysis, skin aging, skin pathology, spatial analysis

Published Open-Access

yes

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