TY - JOUR
T1 - Targeting Cellular Senescence with Senotherapeutics
T2 - Development of New Approaches for Skin Care
AU - Thompson, Elizabeth L.
AU - Pitcher, Louise E.
AU - Niedernhofer, Laura J.
AU - Robbins, Paul D.
N1 - Publisher Copyright:
Copyright © 2022 by the American Society of Plastic Surgeons.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Aging of the skin is evidenced by increased wrinkles, age spots, dryness, and thinning with decreased elasticity. Extrinsic and intrinsic factors including UV, pollution, and inflammation lead to an increase in senescent cells (SnCs) in skin with age that contribute to these observed pathological changes. Cellular senescence is induced by multiple types of damage and stress and is characterized by the irreversible exit from the cell cycle with upregulation of cell cycle-dependent kinase inhibitors p16INK4a and p21CIP1. Most SnCs also developed an inflammatory senescence-associated secretory phenotype (SASP) that drives further pathology through paracrine effects on neighboring cells and endocrine effects on cells at a distance. Recently, compounds able to kill senescent cells specifically, termed senolytics, or suppress the SASP, termed senomorphics, have been developed that have the potential to improve skin aging as well as systemic aging in general. Here, we provide a summary of the evidence for a key role in cellular senescence in driving skin aging. In addition, the evidence for the potential application of senotherapeutics for skin treatments is presented. Overall, topical, and possibly oral senotherapeutic treatments have tremendous potential to eventually become a standard of care for skin aging and related skin disorders.
AB - Aging of the skin is evidenced by increased wrinkles, age spots, dryness, and thinning with decreased elasticity. Extrinsic and intrinsic factors including UV, pollution, and inflammation lead to an increase in senescent cells (SnCs) in skin with age that contribute to these observed pathological changes. Cellular senescence is induced by multiple types of damage and stress and is characterized by the irreversible exit from the cell cycle with upregulation of cell cycle-dependent kinase inhibitors p16INK4a and p21CIP1. Most SnCs also developed an inflammatory senescence-associated secretory phenotype (SASP) that drives further pathology through paracrine effects on neighboring cells and endocrine effects on cells at a distance. Recently, compounds able to kill senescent cells specifically, termed senolytics, or suppress the SASP, termed senomorphics, have been developed that have the potential to improve skin aging as well as systemic aging in general. Here, we provide a summary of the evidence for a key role in cellular senescence in driving skin aging. In addition, the evidence for the potential application of senotherapeutics for skin treatments is presented. Overall, topical, and possibly oral senotherapeutic treatments have tremendous potential to eventually become a standard of care for skin aging and related skin disorders.
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U2 - 10.1097/PRS.0000000000009668
DO - 10.1097/PRS.0000000000009668
M3 - Article
C2 - 36170431
AN - SCOPUS:85138867407
SN - 0032-1052
VL - 150
SP - 12S-19S
JO - Plastic and reconstructive surgery
JF - Plastic and reconstructive surgery
IS - 2 4S
ER -