Senescence-associated secretory phenotype and accelerated renal aging in chronic kidney disease: a new frontier in targeted therapies

Authors

Zayan, Tariq A.; Khafagy, Heba A.

Citation

Arab J Nephrol Transplant. 2026;8(2):54–71. doi: 10.4103/AJNT.AJNT_4_25

Abstract

Chronic kidney disease (CKD) affects over 850 million people globally and represents a paradigm of accelerated biological aging. Cellular senescence, characterized by irreversible growth arrest and the development of a senescence-associated secretory phenotype (SASP), has emerged as a central mechanism driving CKD progression, vascular complications, and systemic frailty. The SASP comprises a complex array of pro-inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes that perpetuate inflammation, fibrosis, and tissue dysfunction. This review synthesizes current understanding of SASP biology in the context of renal aging and inflammaging, examining its contribution to tubular atrophy, glomerulosclerosis, vascular calcification, and the uremic milieu. We critically evaluate emerging senotherapeutic strategies, including senolytic agents (dasatinib, quercetin, navitoclax, fisetin) and senomorphic compounds that modulate SASP secretion, discussing their nephroprotective potential based on preclinical and early clinical evidence. Furthermore, we explore the relevance of cellular senescence in dialysis-dependent patients and kidney transplant recipients, populations characterized by premature aging phenotypes. Finally, we address the translational challenges and opportunities for biomarker development, highlighting how SASP components may serve as both therapeutic targets and prognostic indicators in CKD management.

Full text (excerpt)

Review article 54 Senescence-associated secretory phenotype and accelerated renal aging in chronic kidney disease: a new frontier in targeted therapies Tariq A. Zayan, Heba A. Khafagy Division of Nephrology, Sur Hospital, Sur, Oman Correspondence to Tariq A. Zayan, Consultant Physician, College of Physicians, Division of Nephrology, Sur Hospital, 8220 Sur Hospital St, Sur, Postal Code 411, Sultanate of Oman. Tel: +968-25440000; E-mail: [email protected] Received 20 October 2024 Revised 22 October 2025 Accepted 27 November 2025 Published 29 June 2026 Arab Journal of Nephrology and Transplantation 2026, 8:54–71 Chronic kidney disease (CKD) affects over 850 million people globally and represents a paradigm of accelerated biological aging. Cellular senescence, characterized by irreversible growth arrest and the development of a senescence-associated secretory phenotype (SASP), has emerged as a central mechanism driving CKD progression, vascular complications, and systemic frailty. The SASP comprises a complex array of pro-inflammatory cytokines, chemokines, growth factors, and matrix-degrading enzymes that perpetuate inflammation, fibrosis, and tissue dysfunction. This review synth

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The Arab Journal of Nephrology and Transplantation is the peer-reviewed open-access journal of ASNRT, published since 2008.

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