Endothelial dysfunction in the aging kidney
American Journal of Physiology-Renal Physiology, vol. 328, pp. F542–F562
Abstract
Global population aging is an escalating challenge in modern society, especially as it impairs the function of multiple organs and increases the burden of age-related diseases. The kidneys, in particular, experience function decline, reduced regenerative capacity, and increased susceptibility to injury as they age. As a result, the prevalence of chronic kidney disease (CKD) rises with aging, further contributing to the growing health burden in older populations. One of the key factors in this process is the dysfunction of specialized renal endothelial cells (RECs), which are essential for maintaining kidney health by regulating blood flow and supporting filtration, solute and water reabsorption, and vascular integrity. As the kidneys age, REC dysfunction drives vascular and microenvironmental changes, contributing to the overall decline in kidney function. In this review, we outline the structural and functional effects of aging on the kidney's macrovascular and microvascular compartments and provide a phenotypic description of the aged endothelium. We particularly focus on the molecular and metabolic rewiring driving and sustaining growth-arrested EC senescence phenotype. We finally give an overview of senotherapies acting on ECs, especially of those modulating metabolism. Given that the pathophysiological processes underlying kidney aging largely overlap with those observed in CKD, REC rejuvenation could also benefit patients with CKD. Moreover, such interventions may hold promise in improving the outcomes of aged kidney transplants. Hence, advancing our understanding of REC and kidney aging will create opportunities for innovations that could improve outcomes for both elderly individuals and patients with CKD.
Authors 4
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Mila Borri corresponding
VIB-KU Leuven Center for Cancer Biology · KU Leuven
Affiliation as printed
KU Leuven, VIB Center for Cancer Biology, VIB
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, VIB, Leuven, 3000, Belgium
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Khalifa University of Science and Technology · VIB-KU Leuven Center for Cancer Biology · KU Leuven
Affiliation as printed
KU Leuven, VIB Center for Cancer Biology, VIB
Khalifa University of Science and Technology
Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, VIB, Leuven, 3000, Belgium
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Ton J. Rabelink Aachen Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine
Affiliation as printed
Leiden University Medical Center
Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands
The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands
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Sébastien J. Dumas Aachen Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine
Affiliation as printed
Leiden University Medical Center
Department of Internal Medicine (Nephrology) & Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands
The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands
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