Academic Journal
Targeting cellular senescence in dermatology: senolytic and senomorphic strategies.
| Τίτλος: | Targeting cellular senescence in dermatology: senolytic and senomorphic strategies. |
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| Συγγραφείς: | Haykal D; Centre Laser Palaiseau, 49 Ter Rue de Paris, 91120, Palaiseau, France. docteur.haykal@gmail.com., Flament F; L'Oreal Research & Innovation, Clichy, France., Garibyan L; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Dermatology, Harvard Medical School, Boston, MA, USA., Lee K; Department of Dermatology, Temple University, Philadelphia, PA, USA., Escot J; Helena Rubinstein, L'Oreal Luxury Division, Levallois, France., Gueniche A; Helena Rubinstein, L'Oreal Luxury Division, Levallois, France., Kirkland J; Center for Advanced Gerotherapeutics, Department of Medicine, Pacific Design Center, Cedars-Sinai Health Sciences University, Suite B223.14, 8687 Melrose Avenue, West Hollywood, CA, 90069, USA. |
| Πηγή: | GeroScience [Geroscience] 2026 Oct; Vol. 48 (5), pp. 6343-6352. Date of Electronic Publication: 2026 Jul 08. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101686284 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2509-2723 (Electronic) Linking ISSN: 25092723 NLM ISO Abbreviation: Geroscience Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cham : Springer International Publishing, [2017]- |
| Ιατρικοί όροι (MeSH): | Cellular Senescence*/drug effects , Cellular Senescence*/physiology , Senotherapeutics*/pharmacology , Senotherapeutics*/therapeutic use , Skin Aging*/physiology , Skin Aging*/drug effects , Dermatology*/methods, Geroscience/methods ; Humans ; Senescence-Associated Secretory Phenotype |
| Περίληψη: | Cellular senescence has emerged as a central mechanism driving cutaneous aging, impaired regeneration, and numerous dermatologic pathologies. Initially evolved as a protective mechanism to prevent malignant transformation and facilitate wound repair, senescence becomes maladaptive when senescent cells persist. Senescent keratinocytes, fibroblasts, and melanocytes can secrete pro-inflammatory mediators and other factors, collectively termed the senescence-associated secretory phenotype (SASP), which may degrade extracellular matrix components, disrupt pigmentary balance, and impair barrier function. Senescent cells are resistant to conditions that cause death of non-senescent cells and are generally removed by the immune system. Persisting senescent cells can become increasingly pro-inflammatory and fibrotic, perhaps due to accumulating DNA damage within these cells. Two primary geroscience-based therapeutic paradigms (gerotherapeutics) have been proposed: senolytics, which selectively eliminate senescent cells, and senomorphics, which modulate or suppress SASP activity without inducing senescent cell death. In dermatology, these approaches are particularly relevant given skin's accessibility, visible aging markers, and ability to serve as a translational platform for systemic gerotherapeutic interventions. Interfering with the development of senescent cells, for example by interfering with such regulators of senescent cell formation as p16, retinoblastoma protein (pRB), p53, or p21, can be detrimental due to the protective roles of transient senescence in wound healing and cancer suppression. However, senolytics, which do not prevent senescent cells from developing but rather act by clearing already formed persisting and tissue-damaging senescent cells, offer the potential to delay, prevent, alleviate, or treat aged or fibrotic skin. Because of the days to weeks for senescent cells to form fully and their inability to divide, senolytics can be administered intermittently, for example for brief intervals every 2 weeks or once a month. Senomorphics, conversely, can modulate the detrimental effects of the SASP and generally need to be administered continuously or more frequently than senolytics. Some agents are both senolytic and senomorphic. This review considers the mechanistic underpinnings of senescence in skin, the evidence for both therapeutic approaches, and the future directions for integrating senotherapeutics into regenerative and aesthetic dermatology. Advances in cutaneous biomarkers, topical delivery systems, and AI-assisted patient stratification are expected to accelerate translation into clinical practice. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval: No human or animal studies were conducted; ethical approval was not applicable. Patient consent: Not applicable. Conflict of interest: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Cellular senescence; Cutaneous aging; Gerotherapeutics; SASP; Senolytics; Senomorphics; Skin regeneration |
| Substance Nomenclature: | 0 (Senotherapeutics) |
| Entry Date(s): | Date Created: 20260708 Date Completed: 20260923 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13601383 |
| DOI: | 10.1007/s11357-026-02379-5 |
| PMID: | 42417965 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2509-2723 |
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| DOI: | 10.1007/s11357-026-02379-5 |