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Molecular mechanisms of renal aging
Open accessAbstract
Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney.
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“As individuals age, the kidneys undergo various structural impairments, such as fibrosis, and experience functional issues, including mitochondrial dysfunction (Fig. 3).144–146”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [146]
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
The retinoblastoma protein and cell cycle control
Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90385-2 · Cited by 4,862
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner, C., Inzucchi, S. E., Lachin, J. M., Fitchett, D., von Eynatten, M., Mattheus, M., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Zinman, B. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515920 · Cited by 3,655
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 1×
“Active p53 is able to initiate either apoptosis or senescence via transcriptional upregulation of proapoptotic genes or the cyclin-dependent kinase inhibitor p21CIP1/WAF1, the latter of which inhibits cyclindependent kinases that inactivate the retinoblastoma protein.(52) Hypophosphorylation of the retinoblastoma”
BackgroundNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 392
Chen, L., Yang, T., Lu, D., Zhao, H., Feng, Y., Chen, H., Chen, D., Vaziri, N. D., & Zhao, Y. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.090 · Cited by 363
Sirt3-mediated mitophagy regulates AGEs-induced BMSCs senescence and senile osteoporosis
Guo, Y., Jia, X., Cui, Y., Song, Y., Wang, S., Geng, Y., Li, R., Gao, W., & Fu, D. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101915 · Cited by 299
Immune cells and inflammation in AKI to CKD progression
Sato, Y., & Yanagita, M. (2018) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00195.2018 · Cited by 273
“Functional and structural impairment in aged kidneys as well as chronic inflammatory traits contribute to increased risk for AKI to CKD progression and developing AKI in the elderly (37, 121, 142).”
BackgroundThe ageing kidney: Molecular mechanisms and clinical implications
Fang, Y., Gong, A. Y., Haller, S. T., Dworkin, L. D., Liu, Z., & Gong, R. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101151 · Cited by 223
“donors have declined function, higher risk of graft failure and functional loss, reduced repair capacity after acute rejection, greater susceptibility to ischemia and drug toxicity, and higher incidence of immunogenicity (Li and Wang, 2018; Schmitt and Melk, 2017).”
InfluentialAutophagy in Chronic Kidney Diseases
Lin, T., Wu, V. C., & Wang, C. (2019) · Cells · doi:10.3390/cells8010061 · Cited by 187
“Therefore, a balanced caloric restriction strategy taking into consideration of the autophagy activation is one of the therapeutic options to delay the progression of CKD among elderly patients [100].”
BackgroundHomocysteine and age-associated disorders
Ostrakhovitch, E. A., & TABIBZADEH, S. S. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.10.010 · Cited by 182
Pathophysiology of AKI to CKD progression
Sato, Y., Takahashi, M., & Yanagita, M. (2020) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2020.01.011 · Cited by 181
Tangri, N., Moriyama, T., Schneider, M. P., Virgitti, J. B. J., Nicola, L. D., Arnold, M., Barone, S., Peach, E. J., Wittbrodt, E. T., Chen, H., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2022-067386 · Cited by 142
Targeting angiogenesis and lymphangiogenesis in kidney disease
Tanabe, K., Wada, J., & Sato, Y. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-0260-2 · Cited by 131
Role of hypoxia in cellular senescence
Gao, H., Nepovimová, E., Heger, Z., Valko, M., Wu, Q., Kuča, K., & Adam, V. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106841 · Cited by 131
Immunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126
Waas, T., Schulz, A., Lotz, J., Rossmann, H., Pfeiffer, N., Beutel, M. E., Schmidtmann, I. M., Münzel, T. F., Wild, P. S., & Lackner, K. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-89442-7 · Cited by 114
Curcumin as Prospective Anti-Aging Natural Compound: Focus on Brain
Benameur, T., Soleti, R., Panaro, M. A., Torre, M. E. L., Monda, V., Messina, G., & Porro, C. (2021) · Molecules · doi:10.3390/molecules26164794 · Cited by 104
Cellular senescence is associated with reorganization of the microtubule cytoskeleton
Moujaber, O., Fishbein, F., Omran, N., Liang, Y., Colmegna, I., Presley, J. F., & Stochaj, U. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2999-1 · Cited by 101
Accelerated Kidney Aging in Diabetes Mellitus
Guo, J., Zheng, H., Zhang, W., Lou, W., Xia, C., Han, X. T., Huang, W. J., Zhang, F., Wang, Y., & Liu, W. J. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1234059 · Cited by 100
“The similarities of SASP and the CKD-associated secretory phenotype (CASP) have been compared with one another and may present a link between CKD and renal cellular senescence [67].”
BackgroundInfluentialInflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage
Franzin, R., Stasi, A., Fiorentino, M., Stallone, G., Cantaluppi, V., Gesualdo, L., & Castellano, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00734 · Cited by 93
“Mechanisms of Renal Inflammaging The term renal senescence reflects the complex interplay between genetics, immunological, and hormonal factors able to lead to structural and functional changes observed in aged kidneys (138).”
BackgroundPeritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression
Kida, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218255 · Cited by 93
“Interestingly, the aging process itself accelerates PTC rarefaction [14].”
BackgroundAl‐Dabet, M. M., Shahzad, K., Elwakiel, A., Sulaj, A., Kopf, S., Bock, F. M., Gadi, I., Zimmermann, S., Rana, R., Krishnan, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32477-9 · Cited by 92
Age-related GSK3β overexpression drives podocyte senescence and glomerular aging
Fang, Y., Chen, B., Liu, Z., Gong, A. Y., Gunning, W. T., Ge, Y., Malhotra, D., Gohara, A. F., Dworkin, L. D., & Gong, R. (2022) · Journal of Clinical Investigation · doi:10.1172/jci141848 · Cited by 92
“Some senescence signaling mediators may also regulate the cell cycle (5).”
BackgroundInfluentialAndrikopoulos, P., Aron‐Wisnewsky, J., Chakaroun, R., Myridakis, A., Forslund, S. K., Nielsen, T., Adriouch, S., Holmes, B., Chilloux, J., Vieira‐Silva, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39824-4 · Cited by 88
“In page 22, line#216, R2=0.009, is not consistent to that was shown in page 24 Fig 2, R2=0.0082.”
InfluentialChang-Panesso, M. (2021) · Pediatric Nephrology · doi:10.1007/s00467-020-04849-0 · Cited by 97
Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease
Pippin, J. W., Kaverina, N. V., Wang, Y., Eng, D. G., Zeng, Y., Tran, U., Loretz, C. J., Chang, A., Akilesh, S., Poudel, C., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156250 · Cited by 80
“As expected, when compared with their young counterparts (Figure 3, A and D), staining for senescence-associated β-galactosidase (SA-β-gal) (9) was higher in both glomerular and tubular epithelial cells in aged mice (Figure 3, B and E).”
Cellular senescence and kidney aging
Rex, N., Melk, A., & Schmitt, R. (2023) · Clinical Science · doi:10.1042/cs20230140 · Cited by 89
“Age-associated, very common health conditions such as hypertension, diabetes, cardiovascular disease, and potential exposure to nephrotoxic medications cumulatively increase the risk for AKI and contribute to the transition from AKI to CKD [4,26–28].”
BackgroundSelf-citationLiu, B.-H., Tu, Y., He, W., Liu, Y., Wu, W., Fang, Q., Tang, H., Tang, R., Wan, Z.-Y., Sun, W., et al. (2018) · Aging · doi:10.18632/aging.101723 · Cited by 79
“com 4198 AGING secretory phenotype, SASP) and renal interstitial fibrosis/tubular atrophy (IF/TA) [3-6].”
BackgroundThe impact of senescence on muscle wasting in chronic kidney disease
Huang, Y., Wang, B., Hassounah, F., Price, S. R., Klein, J. D., Mohamed, T., Wang, Y., Park, J., Cai, H., Zhang, X., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13112 · Cited by 71
“For example, p16 cells have been observed in kidney in different types of kidney diseases, including membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, and in transplanted kidneys.(13,14) SA-β-gal and p16 were also increased in kidney epithelial cells of patients with diabetic nephropathy.”
BackgroundStructural and Functional Changes in Aging Kidneys
Dybiec, J., Szlagor, M., Młynarska, E., Rysz, J., & Franczyk, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315435 · Cited by 79
“The activity of p16INK4a, as a senescence mediator, may also be induced by oxidative stress, oncogenic Ras expression, and epigenetic alterations [33].”
BackgroundKlotho and calciprotein particles as therapeutic targets against accelerated ageing
Kuro‐o, M. (2021) · Clinical Science · doi:10.1042/cs20201453 · Cited by 68
Treatment of chronic kidney disease in older populations
Kishi, S., Kadoya, H., & Kashihara, N. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00854-w · Cited by 66
“Mechanistically, processes such as glomerulosclerosis, podocyte hypertrophy, interstitial fibrosis and tubular atrophy, and progressive microvascular rarefaction are involved 27 , exacerbated by factors such as diabetes, obesity and hypertension.”
Podocyte Aging: Why and How Getting Old Matters
Shankland, S. J., Wang, Y., Shaw, A. S., Vaughan, J. C., Pippin, J. W., & Wessely, O. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2021050614 · Cited by 60
Evolution, kidney development, and chronic kidney disease
Chevalier, R. L. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.024 · Cited by 64
Chen, J., Chen, K., Xiao, F., Dai, H., Yang, J. W., Li-ming, W., Wang, X., Jian-guo, Z., & He, Y. (2020) · Kidney International · doi:10.1016/j.kint.2020.03.026 · Cited by 58
“Previous published studies have shown that cell senescence mainly relies on the p16-retinoblastoma and alternative reading frame–p53–p21 signaling pathways.(8,9) Cell senescence plays an important role not only in embryonic development, but also in the progression of major diseases such as diabetes mellitus, cancer, a…”
BackgroundMolecular Mechanisms of Cellular Injury and Role of Toxic Heavy Metals in Chronic Kidney Disease
Mishra, M., Nichols, L., Dave, A. A., Pittman, E. H., Cheek, J. P., Caroland, A. J. V., Lotwala, P., Drummond, J., & Bridges, C. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911105 · Cited by 60
“Senescent cells accumulate in the renal parenchyma, leading to tissue deterioration, fibrosis, and aberrant signaling in different types of cell populations [29,69,78].”
BackgroundMacrophage iron dyshomeostasis promotes aging‐related renal fibrosis
Wu, L., Lin, H., Li, S., Huang, Y., Sun, Y., Shu, S., Luo, T., Liang, T., Lai, W., Rao, J., et al. (2024) · Aging Cell · doi:10.1111/acel.14275 · Cited by 55
“An aging kidney often exhibits diminished filtration function, leading to an elevated prevalence of chronic kidney disease (Fang et al., 2022 ; Luo et al., 2018; Schmitt & Melk, 2017 ).”
C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
Zhang, L., Zhou, F., Yu, X., Zhu, Y., Zhou, Y., Liu, J., Liu, Y., Ma, Q., Zhang, Y., Wang, W., et al. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1933-2 · Cited by 48
Induction of ferroptosis selectively eliminates senescent tubular cells
Liao, C. M., Wulfmeyer, V. C., Chen, R., Erlangga, Z., Sinning, J., von Mäßenhausen, A., Sörensen-Zender, I., Beer, K., von Vietinghoff, S., Haller, H. G., et al. (2022) · American Journal of Transplantation · doi:10.1111/ajt.17102 · Cited by 52
Self-citationMing, X., Yang, Z. R., Huang, Y., Wang, Z., Zhang, Q., Lu, C., Sun, Y., Chen, Y., Zhang, L., Wu, J., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00750-9 · Cited by 55
“Natural aging leads to organ dysfunction, associated diseases or motor dysfunction 52–54 .”
Global transcriptomic changes occur in aged mouse podocytes
Wang, Y., Eng, D. G., Kaverina, N. V., Loretz, C. J., Koirala, A., Akilesh, S., Pippin, J. W., & Shankland, S. J. (2020) · Kidney International · doi:10.1016/j.kint.2020.05.052 · Cited by 50
Pan, H., Feng, W., Chen, M., Luan, H., Hu, Y., Zheng, X., Wang, S., & Mao, Y. (2021) · BioMed Research International · doi:10.1155/2021/6623328 · Cited by 51
“According to the free radical aging theory that was first proposed by Hamann, oxidative stress damage caused by reactive oxygen species (ROS) and free radicals plays an important role in the aging process [3].”
BackgroundEffect of renin–angiotensin system on senescence
Mogi, M. (2020) · Geriatrics & Gerontology International · doi:10.1111/ggi.13927 · Cited by 48
Liu, H.-J., Miao, H., Yang, J.-Z., Liu, F., Cao, G., & Zhao, Y. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101861 · Cited by 51
Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging
Uddin, M. J., Farjana, M., Moni, A., Hossain, K. S., Hannan, M. A., & Ha, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158258 · Cited by 48
“The stable transformation of the kidney structure and its functions in the elderly exhibits a significant reduction in the number of glomeruli (responsible for nephrosclerosis), cortical volume, glomerular filtration rate (GFR), and manifold kidney cysts [3,5,6].”
BackgroundSchnellmann, R., Ntekoumes, D., Choudhury, M. I., Sun, S. X., Zhao, W., & Gerecht, S. (2022) · Advanced Science · doi:10.1002/advs.202201483 · Cited by 45
Cardiovascular Consequences of Uremic Metabolites: an Overview of the Involved Signaling Pathways
Curaj, A., Vanholder, R. C., Loscalzo, J., Quach, K., Wu, Z., Jankowski, V., & Jankowski, J. (2024) · Circulation Research · doi:10.1161/circresaha.123.324001 · Cited by 48
Biomarkers of ageing of humans and non-human primates
Wu, Z., Qu, J. T., Zhang, W., Bao, Z., Bi, Y., Cai, J.-P., Cai, S.-Q., Cao, C.-M., Cao, F., Cao, Z., et al. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00883-8 · Cited by 50
“At the cellular level, aged kidneys primarily demonstrate decreased density and hypertrophy of podocytes 327,329,330 (Supplementary Table 3).”
SerpinB2 Regulates Immune Response in Kidney Injury and Aging
Sen, P., Helmke, A., Liao, C. M., Sörensen-Zender, I., Rong, S., Bräsen, J. H., Melk, A., Haller, H. G., von Vietinghoff, S., & Schmitt, R. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019101085 · Cited by 45
Self-citationYouthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice
Liu, D., Lun, L., Huang, Q., Ning, Y., Zhang, Y., Wang, L., Yin, Z., Zhang, Y., Xia, L., Yin, Z., et al. (2018) · Kidney International · doi:10.1016/j.kint.2018.03.019 · Cited by 44
Sex-Based Differences in Risk Factors and Complications of Chronic Kidney Disease
Wyld, M. L. R., Mata, N. L. D. L., Viecelli, A. K., Swaminathan, R., O’Sullivan, K. M., O’Lone, E., Rowlandson, M., Francis, A., Wyburn, K., & Webster, A. C. (2022) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2022.04.006 · Cited by 44
Li, Q., Chen, C., Chen, X., Han, M., & Li, J. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.05.003 · Cited by 42
Franzin, R., Stasi, A., Ranieri, E., Netti, G. S., Cantaluppi, V., Gesualdo, L., Stallone, G., & Castellano, G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.630419 · Cited by 41
Kidney function and dementia risk in community-dwelling older adults: the Shanghai Aging Study
Wang, M., Ding, D., Zhao, Q., Wu, W., Xiao, Z., Liang, X., Luo, J., & Chen, J. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00729-9 · Cited by 38
Wang, Y., Wang, Y., Yang, M., & Ma, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111191 · Cited by 34
Ellagic acid ameliorates aging-induced renal oxidative damage through upregulating SIRT1 and NRF2
Naghibi, N., Sadeghi, A., Movahedinia, S., Naiini, M. R., Rajizadeh, M. A., Bahri, F., & Nazari‐Robati, M. (2023) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-023-03907-y · Cited by 39
“The aging process is closely connected to enhanced mitochondrial dysfunction and reduced antioxidant capacity leading to redox signaling disruption and a wide range of phenotypic changes, including altered gene expression, arrested cell proliferation and growth, and cellular senescence [3, 4].”
BackgroundYang, S., Sun, D., Wang, L., Wang, X., Shi, M., Jiang, X., & Gao, X. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.10.021 · Cited by 36
14-3-3 proteins: an important regulator of autophagy in diseases.
Jia, H., Liang, Z., Zhang, X., Wang, J., Xu, W., & Qian, H. (2017) · Europe PMC (PubMed Central) · Cited by 33
Hassanein, E. H. M., Ibrahim, I. M., Abd‐alhameed, E. K., Mohamed, N. M., & Ross, S. A. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120697 · Cited by 32
on behalf of SCOPE investigators, Corsonello, A., Tap, L., Roller‐Wirnsberger, R., Wirnsberger, G. H., Zoccali, C., Kostka, T., Guligowska, A., Mattace-Raso, F. U. S., Gil, P., et al. (2018) · BMC Nephrology · doi:10.1186/s12882-018-1030-2 · Cited by 31
“suggests that ageing contributes to the incidence of reduced renal filtration capacity [1].”
BackgroundGoligorsky, M. S. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.01.016 · Cited by 32
Ray, N., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101932 · Cited by 39
Sirtuin 3 in renal diseases and aging: From mechanisms to potential therapies
Xuan, P., Ni, H., Kuang, B., Wang, Z., Hou, S., Gu, S., & Gong, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107261 · Cited by 33
The Role of SIRT3 in the Osteoporosis
Hu, S., & Wang, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.893678 · Cited by 31
“Osteoporosis is a prevalent aging-related disease, which is usually accompanied by changes in metabolic processes and mitochondrial dysfunction (8, 9).”
BackgroundAssociations between nephron number and podometrics in human kidneys
Haruhara, K., Kanzaki, G., Sasaki, T., Hatanaka, S., Okabayashi, Y., Puelles, V. G., Harper, I. S., Shimizu, A., Cullen‐McEwen, L. A., Tsuboi, N., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.07.028 · Cited by 29
Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney
Huang, J., Ladeiras, D., Yu, Y., Ming, X., & Yang, Z. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.582155 · Cited by 29
Recent Advances in Epigenetics of Age-Related Kidney Diseases
Liu, F., Chen, J., Li, Z., & Meng, X. (2022) · Genes · doi:10.3390/genes13050796 · Cited by 31
“The main pathological characteristics of the aged kidney include arteriosclerosis, glomerulosclerosis, tubular atrophy, and interstitial fibrosis [7].”
BackgroundRenal inflamm-aging provokes intra-graft inflammation following experimental kidney transplantation
He, A., Sarwar, A., Thole, L. M. L., Siegle, J., Sattler, A., Ashraf, M., Proß, V., Stahl, C., Dornieden, T., Bergmann, Y., et al. (2022) · American Journal of Transplantation · doi:10.1111/ajt.17154 · Cited by 30
Endothelial dysfunction in the aging kidney
Borri, M., Jacobs, M. E., Carmeliet, P., Rabelink, T. J., & Dumas, S. J. (2025) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00287.2024 · Cited by 31
Chen, C.-C., Chang, Z., Tsai, F., & Chen, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186766 · Cited by 28
“This renal aging results in reduced capacities for adaption to stress and structural repair [25].”
BackgroundProteasome activator PA200 maintains stability of histone marks during transcription and aging
Jiang, T.-X., Ma, S., Han, X., Luo, Z.-Y., Zhu, Q., Chiba, T., Xie, W., Chen, S., Lin, K., & Qiu, X. (2020) · Theranostics · doi:10.7150/thno.48744 · Cited by 29
Anti-senescence therapies: a new concept to address cardiovascular disease
Stojanović, S. D., Thum, T., & Bauersachs, J. K. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf030 · Cited by 31
Xiong, Y., Huang, W., Ling, X., Zhou, S. Y., Wang, X., Li, X., & Zhou, L. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01298-5 · Cited by 28
“Currently, there are a bunch of theories suggesting the mechanisms of aging, such as oxidative stress [12], telomere shortening [13], protein homeostasis imbalance [14], epigenetic changes, DNA damage, and persistent in fl ammation [15].”
Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis
Yang, C., Xue, J., An, N., Huang, X.-J., Wu, Z., Ye, L., Li, Z., Wang, S., Pan, Q., Liang, D., et al. (2018) · Medical Science Monitor · doi:10.12659/msm.909353 · Cited by 26
“Recently, cellular senescence has been reported to play a causal role in the pathogenesis of glomerular diseases [19].”
BackgroundStille, K., Kribben, A., & Herget‐Rosenthal, S. (2022) · Journal of Nephrology · doi:10.1007/s40620-022-01381-2 · Cited by 31
El‐Horany, H. E., Gaballah, H. H., & Helal, D. S. (2018) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2018.1499117 · Cited by 24
“In renal aging, a complex interplay of genetics, environmental change, and cellular dysfunction leads to characteristic structural and functional changes (Schmitt and Melk 2017).”
BackgroundGenetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR
Wang, Q., Qi, H., Wu, Y., Yu, L., Bouchareb, R., Li, S., Lassén, E., Casalena, G., Stadler, K., Ebefors, K., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00776-0 · Cited by 26
Deciphering the whale's secrets to have a long life
Lagunas‐Rangel, F. A. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111425 · Cited by 23
The interaction between cellular senescence and chronic kidney disease as a therapeutic opportunity
Zhao, J.-L., Qiao, X.-H., Mao, J., Liu, F., & Fu, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.974361 · Cited by 24
“, 2019), and the autophagic flux induced by calorie restriction (CR) (Schmitt and Melk, 2017) can slow down the process of renal tubular atrophy and interstitial fibrosis.”
BackgroundSaadat, Y. R., Abbasi, A., Hejazian, S. S., Hekmatshoar, Y., Ardalan, M., Farnood, F., & Vahed, S. Z. (2025) · BMC Nephrology · doi:10.1186/s12882-025-04057-8 · Cited by 24
“…across many renal pathologies, notably IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and in transplanted kidneys [58, 59]. p16 INK4a and senescence-associated beta-galactosidase (SA-β-gal) were likewise elevated in the kidney epithelium of individuals with…”
Podocyte FFAR4 deficiency aggravated glomerular diseases and aging
Yin, T., Yang, L., Tang, L., Li, J., Liu, D., Guo, F., Mu, Y., Wu, Q., Feng, Y., Tan, Z., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.05.035 · Cited by 21
PPARα/β Activation Alleviates Age-Associated Renal Fibrosis in Sprague Dawley Rats
Chung, K. W., Ha, S., Kim, S. M., Kim, D. H., An, H. J., Lee, E. K., Moon, H. R., & Chung, H. Y. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz083 · Cited by 21
Xiao, Q. (2022) · Renal Failure · doi:10.1080/0886022x.2022.2056485 · Cited by 21
RetractedBoivin, E., Daré, B. L., Bellay, R., Vigneau, C. M., Mercerolle, M., & Bacle, A. (2023) · International Journal of Bipolar Disorders · doi:10.1186/s40345-023-00286-8 · Cited by 21
“3 times more rapid compared to the general population where mean annual GFR loss is estimated at approximately 1 mL/min/1.73 m2 (Glassock and Rule 2016; Nankivell 2001; Schmitt and Melk 2017).”
BackgroundInfluentialSGLT2 inhibition to target kidney aging
Russo, E., Zanetti, V., Macciò, L., Benizzelli, G., Carbone, F., Porta, E. L., Esposito, P. B., Verzola, D., Garibotto, G., & Viazzi, F. C. (2024) · Clinical Kidney Journal · doi:10.1093/ckj/sfae133 · Cited by 22
“Physiologic kidney aging and several kidney diseases share common biologic processes and molecular pathways [1 ], including cellular senescence, inflammation, fibrosis, vascular rarefaction, loss of glomeruli and tubular dysfunction, which lead to glomerulosclerosis and tubulointerstitial fibrosis…”
BackgroundComplement C3 deficiency ameliorates aging related changes in the kidney
Wu, X., Lin, L., Cui, J., Chen, Y., Yang, L., & Wan, J. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118370 · Cited by 19
Gupta, S., Mandal, S., Banerjee, K., Almarshood, H., Pushpakumar, S. B., & Sen, U. (2024) · Biomolecules · doi:10.3390/biom14091165 · Cited by 23
“Although the kidney undergoes structural and functional changes with aging, there are little data regarding the underlying mechanism [111].”
BackgroundBaba, M., Takatsuna, H., Matsui, N., & Ohwada, S. (2020) · Journal of Pain Research · doi:10.2147/jpr.s255345 · Cited by 20
Luca, F. D., Camporeale, V., Leccese, G., Cuttano, R., Troise, D. E., Infante, B., Stallone, G., Netti, G. S., & Ranieri, E. (2025) · Cells · doi:10.3390/cells14221831 · Cited by 23
“Senescent cells in the kidney release SASP factors, which promote inflammation and fibrosis, further exacerbating renal damage and functional decline [115].”
Metformin Protects against Podocyte Injury in Diabetic Kidney Disease
Lehtonen, S. H. (2020) · Pharmaceuticals · doi:10.3390/ph13120452 · Cited by 20
“As the kidney ages, the GFR and the number of nephrons decrease, and the renal cells acquire a senescent phenotype [159].”
BackgroundSinning, J., Funk, N. D., Sörensen-Zender, I., Wulfmeyer, V. C., Liao, C. M., Haller, H. G., Hinze, C., Schmidt-Ott, K. M., Melk, A., & Schmitt, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1222339 · Cited by 21
“Aging leads to the loss of glomeruli and to atrophy and functional alterations of tubular cells (1).”
BackgroundSelf-citationA high-resolution view of the heterogeneous aging endothelium
Dobner, S., Tóth, F., & de Rooij, L. P. M. H. (2024) · Angiogenesis · doi:10.1007/s10456-023-09904-6 · Cited by 22
“Moreover, age-induced alterations of ECs, such as decreased eNos and increased Et-1 expression, lead to an impaired regulation of vascular tone [104–106]. scRNA-seq has revealed a remarkably degree of heterogeneous ECs, which can be classified into ECs belonging to the glomeruli, as well as the…”
BackgroundStress Pathways in Chronic Kidney Disease: Linking Cortisol, Oxidative Stress, and Inflammation
Motrenikova, M., Boyanov, K., Bojinova, N., & Bivolarska, A. V. (2025) · Antioxidants · doi:10.3390/antiox14101259 · Cited by 21
“As renal function declines, this redox imbalance becomes progressively more pronounced, contributing to tubular atrophy, glomerulosclerosis, and the acceleration of cardiovascular complications [13].”
Efficacy of dotinurad in patients with severe renal dysfunction
Kurihara, O., Yamada, T., Kato, K., & Miyauchi, Y. (2023) · Clinical and Experimental Nephrology · doi:10.1007/s10157-023-02419-w · Cited by 21
Ai, S., Li, Y., Zheng, H., Wang, Z., Liu, W., Tao, J., Li, Y., & Wang, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1275792 · Cited by 17
Baisantry, A., Berkenkamp, B., Rong, S., Bhayadia, R., Sörensen-Zender, I., Schmitt, R., & Melk, A. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00333.2018 · Cited by 17
“This might be a key step in the transition from acute to chronic kidney injury (27).”
BackgroundSelf-citationYu, G., Nakano, D., Zhang, Y., Li, L., Tian, Y., & Nishiyama, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-46994-z · Cited by 17
Comparative proteomic analysis identifies biomarkers for renal aging
Yi, M., Ma, Y., Zhu, S., Luo, C., Chen, Y., Wang, Q., & Deng, H. (2020) · Aging · doi:10.18632/aging.104007 · Cited by 17
“Age-associated modifications of kidneys include changes in glomerular structure, such as glomerular basement membrane thickening or wrinkling associated with loss of capillary loops, and mesangial matrix expansion [2, 3].”
BackgroundRejuvenation: Turning back the clock of aging kidney
Wei, S.-Y., Pan, S., Li, B., Chen, Y., & Lin, S. (2019) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2019.05.020 · Cited by 18
Bioenergetics: the evolutionary basis of progressive kidney disease
Chevalier, R. L. (2023) · Physiological Reviews · doi:10.1152/physrev.00029.2022 · Cited by 17
Kim, J. W., Nam, S. A., Koh, E. S., Kim, H. W., Kim, S., Woo, J. J., & Kim, Y. K. (2024) · Antioxidants · doi:10.3390/antiox13080886 · Cited by 16
“Aging induces the accumulation of damaged proteins, lipids, organelles, and mitochondria, which are physiological causes of the age-associated impairment of cellular function and limit the capacity for regeneration [2].”
BackgroundZhang, Y., Ni, X., Lu, W., Yu, Y., Zhu, B. L., Bai, Y., Pei, X., Gao, F., Guo, L., Yong, Z., et al. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111774 · Cited by 17
Metadata
- Authors
- Schmitt, R., & Melk, A.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 92
- Issue
- 3
- Pages
- 569-579
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2737090018
- Cited by
- 235
- References
- 149
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 31 · 2023: 32 · 2022: 30 · 2021: 32 · 2020: 29 · 2019: 19 · 2018: 15 · 2017: 2
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- kidney aging, acute kidney injury, chronic kidney disease, glomerular filtration rate decline, nephron loss, podocyte hypertrophy, glomerulosclerosis, tubular atrophy, microvascular rarefaction, cellular senescence, senolytics, autophagy, renal inflammation, caloric restriction mimetics, renin-angiotensin-aldosterone system inhibition, kidney regeneration
- MeSH terms
- Aging, Angiotensin-Converting Enzyme Inhibitors, Animals, Autophagy, Disease Models, Animal, Disease Susceptibility, Glomerular Filtration Rate, Humans, Kidney, Renin-Angiotensin System, Cellular Senescence, Caloric Restriction, Acute Kidney Injury
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