Cellular senescence in skin‐related research: Targeted signaling pathways and naturally occurring therapeutic agents

Abstract

Despite the growing interest by researchers into cellular senescence, a hallmark of cellular aging, its role in human skin remains equivocal. The skin is the largest and most accessible human organ, reacting to the external and internal environment. Hence, it is an organ of choice to investigate cellular senescence and to target root‐cause aging processes using senolytic and senomorphic agents, including naturally occurring plant‐based derivatives. This review presents different aspects of skin cellular senescence, from physiology to pathology and signaling pathways. Cellular senescence can have both beneficial and detrimental effects on the skin, indicating that both prosenescent and antisenescent therapies may be desirable, based on the context. Knowledge of molecular mechanisms involved in skin cellular senescence may provide meaningful insights for developing effective therapeutics for senescence‐related skin disorders, such as wound healing and cosmetic skin aging changes.

Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

“…Several dozen new senolytic agents have been discovered and are currently being tested extensively. When targeting senescent cells in vivo, it is important to recognize that cellular senescence is a mechanism that prevents tumorigenesis and is important during embryogenesis, possibly wound healing (although removing senescent cells appears to enhance healing of chronic wounds [302,303], and host immunity. The distinction between physiological, beneficial senescence and pathological senescence is crucial, especially the impact of persistent senescent cells that have evaded removal by the immune system.…”

Cellular senescence and wound healing in aged and diabetic skin

“…Cellular senescence plays a crucial role in wound healing and is a driving force for the manifestation of the aging phenotype of the skin ( Wlaschek et al, 2021 ; Shin et al, 2023 ). Senescent fibroblasts, melanocytes, and keratinocytes that accumulate in aging skin exhibit typical senescence features, such as increased expression of p16, p21, and p53, elevated activity of SA-βgal, diminished expression of nuclear lamin-B1, and extranuclear diffusion of high mobility group box 1 (HMGB1) ( Wang and Dreesen, 2018 ; Dańczak-Pazdrowska et al, 2023 ). Keratinocytes are continually turned over by desquamation, which usually prevents the accumulation of senescent cells.…”

“…Repetitive ultra-violet B (UVB) stimulation promotes the accumulation of senescent keratinocytes ( Chambers and Vukmanovic-Stejic, 2020 ; Bauwens et al, 2023 ). Accumulation of senescent fibroblasts in the skin correlates with aging and UVB-induced senescent keratinocyte accumulation ( Ressler et al, 2006 ; Dańczak-Pazdrowska et al, 2023 ). Senescent fibroblasts exacerbate the inflammatory phenotype of the tissue through the expression of SASP factors such as IL-6 and IL-8 via NF-κB, ( Meyer et al, 2017 ; Pilkington et al, 2021 ), leading to the induction of melanocyte differentiation through stromal-epithelial interactions promoted by stromal cell-derived factor 1 (SDF-1) deficiency, ultimately resulting in senile pigmentation ( Yoon et al, 2018 ).…”

The Promising Role of Polyphenols in Skin Disorders

“…Membrane peroxidation and the accumulation of ROS peroxidation have been detected in melanocytes and keratinocytes situated in unaffected regions of vitiligo. In addition, the cytokines IL-1, IL-6, and TNF significantly increase the production of IL-8 in melanocytes, resulting in oxidative stress and the programmed cell death of keratinocytes and melanocytes [ 143 ]. This disease demonstrates a worldwide occurrence, unaffected by variables such as age and gender.…”