Document Type : Review Article
Authors
1
Department of Basic Medical Sciences, Faculty of Medicine, Abadan University of Medical Sciences, Abadan, Iran
2
Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
3
Workplace Health Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
4
Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran
5
Department of Medical Genetics and Molecular Medicine, School of Medicine, University of Medical Sciences, Mashhad, Iran
6
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
ABSTRACT
Background: Salt-sensitive hypertension (SSHTN) is a multifactorial cardiovascular–renal disorder whose prevalence increases with aging. It contributes to cardiovascular disease, chronic kidney disease, frailty, and progressive target-organ injury. Beyond excessive sodium intake, SSHTN reflects systemic impairment of sodium homeostasis involving nephron loss, impaired pressure–natriuresis, endothelial dysfunction, arterial stiffening, immune dysregulation, mitochondrial impairment, and epigenetic remodeling.
Methods: This review summarizes and integrates current evidence on aging-associated SSHTN, focusing on epidemiology, biological mechanisms, multiorgan consequences, and emerging therapeutic strategies.
Results: Evidence indicates that aging links sodium excess to vascular and renal injury through several interconnected pathways, including non-osmotic tissue sodium accumulation, endothelial glycocalyx disruption, inflammaging, immunosenescence, cellular senescence, clonal hematopoiesis, gut microbiome remodeling, and mitochondrial dysfunction. Genetic and epigenetic alterations further contribute to impaired sodium handling, vascular dysfunction, and renal injury. These findings support the concept that SSHTN is a systems-level manifestation of biological aging rather than a purely renal disorder. Emerging therapeutic strategies include RNA therapeutics, senotherapeutic approaches, microbiome- and mitochondria-targeted interventions, regenerative cell-based therapies, and precision medicine frameworks.
Conclusion: Aging-associated SSHTN represents a multisystem disorder driven by impaired sodium handling and age-related biological changes across the kidney, vasculature, immune system, and metabolic networks. Available evidence underscores the need for mechanism-driven, biologically informed, and precision-guided strategies to improve prevention and treatment in older adults.
Keywords
Healthy Aging Perspectives