SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights

Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation...

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Main Authors: Saud Alqahtani, Taha Alqahtani, Krishnaraju Venkatesan, Durgaramani Sivadasan, Rehab Ahmed, Nizar Sirag, Hassabelrasoul Elfadil, Hanem Abdullah Mohamed, Haseena T.A., Rasha Elsayed Ahmed, Pooja Muralidharan, Premalatha Paulsamy
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/8/608
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author Saud Alqahtani
Taha Alqahtani
Krishnaraju Venkatesan
Durgaramani Sivadasan
Rehab Ahmed
Nizar Sirag
Hassabelrasoul Elfadil
Hanem Abdullah Mohamed
Haseena T.A.
Rasha Elsayed Ahmed
Pooja Muralidharan
Premalatha Paulsamy
author_facet Saud Alqahtani
Taha Alqahtani
Krishnaraju Venkatesan
Durgaramani Sivadasan
Rehab Ahmed
Nizar Sirag
Hassabelrasoul Elfadil
Hanem Abdullah Mohamed
Haseena T.A.
Rasha Elsayed Ahmed
Pooja Muralidharan
Premalatha Paulsamy
author_sort Saud Alqahtani
collection DOAJ
description Cellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, and tumorigenesis. This review examines SASP’s molecular regulation, dual roles in health and pathology, and therapeutic potential. The following two main strategies are explored: senescence clearance, which eliminates SASP-producing cells, and SASP modulation, which refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, and cGAS-STING, are discussed alongside pharmacological, immunotherapeutic, gene-editing, and epigenetic interventions. SASP heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, and ethical considerations. SASP modulation emerges as a promising strategy for aging, oncology, and tissue repair, with future advancements relying on multi-omics and AI-driven insights to optimize clinical outcomes.
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spelling doaj-art-9477db00be2b4aefb4dc5747e7df5d152025-08-20T03:14:20ZengMDPI AGCells2073-44092025-04-0114860810.3390/cells14080608SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular InsightsSaud Alqahtani0Taha Alqahtani1Krishnaraju Venkatesan2Durgaramani Sivadasan3Rehab Ahmed4Nizar Sirag5Hassabelrasoul Elfadil6Hanem Abdullah Mohamed7Haseena T.A.8Rasha Elsayed Ahmed9Pooja Muralidharan10Premalatha Paulsamy11Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62521, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, King Khalid University, Abha 62521, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, King Khalid University, Abha 62521, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDivision of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi ArabiaDivision of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi ArabiaPediatric Nursing, College of Nursing, King Khalid University, Abha 62521, Saudi ArabiaCollege of Nursing, Mahalah Branch for Girls, King Khalid University, Abha 62521, Saudi ArabiaMedical Surgical Nursing, Tanta University, Tanta 31527, EgyptUndergraduate Program, PSG College of Pharmacy, Peelamedu, Coimbatore 641004, IndiaCollege of Nursing, Mahalah Branch for Girls, King Khalid University, Abha 62521, Saudi ArabiaCellular senescence regulates aging, tissue maintenance, and disease progression through the Senescence-Associated Secretory Phenotype (SASP), a secretory profile of cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While transient SASP aids wound healing, its chronic activation drives inflammation, fibrosis, and tumorigenesis. This review examines SASP’s molecular regulation, dual roles in health and pathology, and therapeutic potential. The following two main strategies are explored: senescence clearance, which eliminates SASP-producing cells, and SASP modulation, which refines secretion to suppress inflammation while maintaining regenerative effects. Key pathways, including NF-κB, C/EBPβ, and cGAS-STING, are discussed alongside pharmacological, immunotherapeutic, gene-editing, and epigenetic interventions. SASP heterogeneity necessitates tissue-specific biomarkers for personalized therapies. Challenges include immune interactions, long-term safety, and ethical considerations. SASP modulation emerges as a promising strategy for aging, oncology, and tissue repair, with future advancements relying on multi-omics and AI-driven insights to optimize clinical outcomes.https://www.mdpi.com/2073-4409/14/8/608cellular senescencesenescence-associated secretory phenotype (SASP)cellular rejuvenationaging and tissue homeostasisSASP modulation strategies
spellingShingle Saud Alqahtani
Taha Alqahtani
Krishnaraju Venkatesan
Durgaramani Sivadasan
Rehab Ahmed
Nizar Sirag
Hassabelrasoul Elfadil
Hanem Abdullah Mohamed
Haseena T.A.
Rasha Elsayed Ahmed
Pooja Muralidharan
Premalatha Paulsamy
SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
Cells
cellular senescence
senescence-associated secretory phenotype (SASP)
cellular rejuvenation
aging and tissue homeostasis
SASP modulation strategies
title SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
title_full SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
title_fullStr SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
title_full_unstemmed SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
title_short SASP Modulation for Cellular Rejuvenation and Tissue Homeostasis: Therapeutic Strategies and Molecular Insights
title_sort sasp modulation for cellular rejuvenation and tissue homeostasis therapeutic strategies and molecular insights
topic cellular senescence
senescence-associated secretory phenotype (SASP)
cellular rejuvenation
aging and tissue homeostasis
SASP modulation strategies
url https://www.mdpi.com/2073-4409/14/8/608
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