切换至 "中华医学电子期刊资源库"

中华老年病研究电子杂志 ›› 2025, Vol. 12 ›› Issue (03) : 39 -46. doi: 10.3877/cma.j.issn.2095-8757.2025.03.006

综述

肾脏衰老研究进展
欧阳卿, 何茹琨, 陈军()   
  1. 310013 杭州,浙江医院
  • 收稿日期:2025-06-21 出版日期:2025-08-28
  • 通信作者: 陈军

Progress in research on kidney aging

Qing Ouyang, Rukun He, Jun Chen()   

  1. Zhejiang Hospital, Hangzhou 310013, China
  • Received:2025-06-21 Published:2025-08-28
  • Corresponding author: Jun Chen
引用本文:

欧阳卿, 何茹琨, 陈军. 肾脏衰老研究进展[J/OL]. 中华老年病研究电子杂志, 2025, 12(03): 39-46.

Qing Ouyang, Rukun He, Jun Chen. Progress in research on kidney aging[J/OL]. Chinese Journal of Geriatrics Research(Electronic Edition), 2025, 12(03): 39-46.

肾脏作为人体重要的代谢和排泄器官,承担着清除代谢废物、调节水盐平衡和维持酸碱稳态等关键生理功能。随年龄增长,肾脏会出现进行性功能衰退,并伴随显著的宏观和微观组织学变化。这种与年龄相关的肾功能损害已成为临床亟待解决的重要问题。深入研究肾脏衰老的病理特征,对于理解并改善年龄相关性肾损伤具有重要意义。从分子机制层面看,细胞衰老在肾脏衰老进程中起着决定性作用,并涉及多种细胞信号转导通路。这些通路为延缓甚至逆转肾脏衰老提供了潜在的干预靶点。因此,系统性研究肾脏衰老的分子机制及其临床意义,对于临床的早期诊断、肾脏衰老的延缓、肾脏疾病新治疗策略的开发具有重要价值。本文重点阐述肾脏衰老的病理特征、分子机制及潜在的治疗方向,为相关研究和临床实践提供新思路。

The kidneys, as an important metabolic and excretory organ in the human body, undertake crucial physiological functions such as eliminating metabolic waste, regulating water and salt balance, and maintaining acid-base homeostasis. With the increase of age, the kidneys undergo progressive functional decline, accompanied by significant macroscopic and microscopic histological changes. This age-related renal function impairment has become an important issue urgently needing to be addressed in clinical practice. In-depth research on the pathological features of kidney aging is of great significance for understanding and improving age-related renal injury. From the molecular mechanism perspective, cellular aging plays a decisive role in the aging process of the kidneys and involves multiple cell signal transduction pathways. These pathways provide potential intervention targets for delaying or reversing kidney aging. Therefore, systematic research on the molecular mechanism of kidney aging and its clinical significance is of great value for the early diagnosis in clinical practice, the delay of kidney aging, and the development of new treatment strategies for kidney diseases. This article focuses on the pathological features, molecular mechanisms, and potential treatment directions of kidney aging, providing new ideas for related research and clinical practice.

[1]
Long DA, Mu W, Price KL, et al. Blood vessels and the aging kidney[J]. Nephron Exp Nephrol, 2005, 101(3):95-99.
[2]
Scholz H, Boivin FJ, Schmidt-Ott KM, et al. Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection[J]. Nat Rev Nephrol, 2021, 17(5):335-349.
[3]
Roseman DA, Hwang SJ, Oyama-Manabe N, et al. Clinical associations of total kidney volume: the Framingham Heart Study[J]. Nephrol Dial Transplant, 2017, 32(8):1344-1350.
[4]
Wang X, Vrtiska TJ, Avula RT, et al. Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney[J]. Kidney Int, 2014, 85(3):677-685.
[5]
Hodgin JB, Bitzer M, Wickman L, et al. Glomerular aging and focal global glomerulosclerosis: a podometric perspective[J]. J Am Soc Nephrol, 2015, 26(12):3162-3178.
[6]
Verzola D, Gandolfo MT, Gaetani G, et al. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2008, 295(5):1563-1573.
[7]
Wiggins JE. Aging in the glomerulus[J]. J Gerontol A Biol Sci Med Sci, 2012, 67(12):1358-1364.
[8]
Melk A, Schmidt BM, Takeuchi O, et al. Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney[J]. Kidney Int, 2004, 65(2):510-520.
[9]
Jin H, Zhang Y, Ding Q, et al. Epithelial innate immunity mediates tubular cell senescence after kidney injury[J]. JCI insight, 2019, 4(2):e125490.
[10]
Li Z, Wang Z. Aging kidney and aging-related disease[J]. Adv Exp Med Biol, 2018, 1086:169-187.
[11]
Luo C, Zhou S, Zhou Z, et al. Wnt9a promotes renal fibrosis by accelerating cellular senescence in tubular epithelial cells[J]. J Am Soc Nephrol, 2018, 29(4):1238-1256.
[12]
Dumas SJ, Meta E, Borri M, et al. Phenotypic diversity and metabolic specialization of renal endothelial cells[J]. Nat Rev Nephrol, 2021, 17(7):441-464.
[13]
Schmitt R, Melk A. Molecular mechanisms of renal aging[J]. Kidney international, 2017, 92(3):569-579.
[14]
Chou YH, Chen YM. Aging and renal disease: old questions for new challenges[J]. Aging Dis, 2021, 12(2):515-528.
[15]
Chen J, Sivan U, Tan SL, et al. High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging[J]. Sci Adv, 2021, 7(6):eabd7819.
[16]
Wada Y, Umeno R, Nagasu H, et al. Endothelial dysfunction accelerates impairment of mitochondrial function in ageing kidneys via inflammasome activation[J]. Int J Molecul Sci, 2021, 22(17):9269.
[17]
Jourde-Chiche N, Fakhouri F, Dou L, et al. Endothelium structure and function in kidney health and disease[J]. Nat Rev Nephrol, 2019, 15(2):87-108.
[18]
Westhoff JH, Hilgers KF, Steinbach MP, et al. Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a[J]. Hypertension, 2008, 52(1):123-129.
[19]
Bax L, van der Graaf Y, Rabelink AJ, et al. Influence of atherosclerosis on age-related changes in renal size and function[J]. Eur J Clin Inves, 2003, 33(1):34-40.
[20]
Lacolley P, Regnault V, Avolio AP. Smooth muscle cell and arterial aging: basic and clinical aspects[J]. Cardiovascul Res, 2018, 114(4):513-528.
[21]
Mas-Bargues C, Borrás C, Alique M. The contribution of extracellular vesicles from senescent endothelial and vascular smooth muscle cells to vascular calcification[J]. Front Cardiovascul Med, 2022, 9:854726.
[22]
Chappell J, Harman JL, Narasimhan VM, et al. Extensive proliferation of a subset of differentiated, yet plastic, medial vascular smooth muscle cells contributes to neointimal formation in mouse injury and atherosclerosis models[J]. Circul Research, 2016, 119(12):1313-1323.
[23]
Ho CY, Shanahan CM. Medial arterial calcification: an overlooked player in peripheral arterial disease[J]. Arterioscler Thromb Vasc Biol, 2016, 36(8):1475-1482.
[24]
Hutcheson JD, Goettsch C. Cardiovascular calcification heterogeneity in chronic kidney disease[J]. Circul Res, 2023, 132(8):993-1012.
[25]
Satoh M, Kidokoro K, Ozeki M, et al. Angiostatin production increases in response to decreased nitric oxide in aging rat kidney[J]. Lab Invest, 2013, 93(3):334-343.
[26]
Stefanska A, Eng D, Kaverina N, et al. Interstitial pericytes decrease in aged mouse kidneys[J]. Aging, 2015, 7(6):370-382.
[27]
Jacobs ME, de Vries DK, Engelse MA, et al. Endothelial to mesenchymal transition in kidney fibrosis[J]. Nephrol Dial Transplant, 2024, 39(5):752-760.
[28]
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains[J]. Exp Cell Res, 1961, 25:585-621.
[29]
Sturmlechner I, Durik M, Sieben CJ, et al. Cellular senescence in renal ageing and disease[J]. Nat Rev Nephrol, 2017, 13(2):77-89.
[30]
Akbar AN, Henson SM, Lanna A. Senescence of T lymphocytes: implications for enhancing human immunity[J]. Trend Immunol, 2016, 37(12):866-876.
[31]
Gorgoulis V, Adams PD, Alimonti A, et al. Cellular senescence: defining a path forward[J]. Cell, 2019, 179(4):813-827.
[32]
van Deursen JM. The role of senescent cells in ageing[J]. Nature, 2014, 509(7501):439-446.
[33]
von Zglinicki T. Oxidative stress shortens telomeres[J]. Trend Bio Sci, 2002, 27(7):339-344.
[34]
Sedelnikova OA, Horikawa I, Zimonjic DB, et al. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks[J]. Nat Cell Biol, 2004, 6(2):168-170.
[35]
Wiley CD, Velarde MC, Lecot P, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype[J]. Cell Metabol, 2016, 23(2):303-314.
[36]
Petrova NV, Velichko AK, Razin SV, et al. Small molecule compounds that induce cellular senescence[J]. Aging Cell, 2016, 15(6):999-1017.
[37]
Nehme J, Borghesan M, Mackedenski S, et al. Cellular senescence as a potential mediator of COVID-19 severity in the elderly[J]. Aging Cell, 2020, 19(10):e13237.
[38]
Lee S, Yu Y, Trimpert J, et al. Virus-induced senescence is a driver and therapeutic target in COVID-19[J]. Nature, 2021, 599(7884):283-289.
[39]
Wen J, Zeng M, Shu Y, et al. Aging increases the susceptibility of cisplatin-induced nephrotoxicity[J]. Age, 2015, 37(6):112.
[40]
Wolstein JM, Lee DH, Michaud J, et al. INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction[J]. Am J Physiol Renal Physiol, 2010, 299(6):F1486-1495.
[41]
Jun JI, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing[J]. Nat Cell Biol, 2010, 12(7):676-685.
[42]
Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan[J]. Nature, 2016, 530(7589):184-189.
[43]
Schmitt R, Susnik N, Melk A. Molecular aspects of renal senescence[J]. Curr Opin Organ Transplant, 2015, 20(4):412-416.
[44]
von Zglinicki T, Wan T, Miwa S. Senescence in post-mitotic cells: a driver of aging[J]? Antioxid Redox Signal, 2021, 34(4):308-323.
[45]
López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153(6):1194-1217.
[46]
Kurz DJ, Decary S, Hong Y, et al. Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells[J]. J Cell Sci, 2000, 113 (Pt 20):3613-3622.
[47]
Mosteiro L, Pantoja C, de Martino A, et al. Senescence promotes in vivo reprogramming through p16(INK)(4a) and IL-6[J]. Aging cell, 2018, 17(2):e12711.
[48]
Prata L, Ovsyannikova IG, Tchkonia T, et al. Senescent cell clearance by the immune system: emerging therapeutic opportunities[J]. Semin Immunol, 2018, 40:101275.
[49]
Ritschka B, Storer M, Mas A, et al. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration[J]. Genes Devel, 2017, 31(2):172-183.
[50]
Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence[J]. Nat Rev Cancer, 2015, 15(7):397-408.
[51]
Wiley CD, Flynn JM, Morrissey C, et al. Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence[J]. Aging Cell, 2017, 16(5):1043-1050.
[52]
Sanders YY, Liu H, Zhang X, et al. Histone modifications in senescence-associated resistance to apoptosis by oxidative stress[J]. Redox Biol, 2013, 1(1):8-16.
[53]
Rayess H, Wang MB, Srivatsan ES. Cellular senescence and tumor suppressor gene p16[J]. Int J Cancer, 2012, 130(8):1715-1725.
[54]
Sopjani M, Rinnerthaler M, Kruja J, et al. Intracellular signaling of the aging suppressor protein Klotho[J]. Curr Mole Med, 2015, 15(1):27-37.
[55]
Chuang PY, Cai W, Li X, et al. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice[J]. Am J Physiol Renal Physiol, 2017, 313(3):F621-F628.
[56]
Fang Y, Chen B, Liu Z, et al. Age-related GSK3β overexpression drives podocyte senescence and glomerular aging[J]. J Clin Invest, 2022, 132(4):e141848.
[57]
Zarse K, Terao T, Tian J, et al. Low-dose lithium uptake promotes longevity in humans and metazoans[J]. Eur J Nut, 2011, 50(5):387-389.
[58]
Zhou S, Wang P, Qiao Y, et al. Genetic and pharmacologic targeting of glycogen synthase kinase 3β reinforces the Nrf2 antioxidant defense against podocytopathy[J]. J Am Soc Nephrol, 2016, 27(8):2289-2308.
[59]
Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility[J]. Cell, 2015, 160(5):816-827.
[60]
O'Sullivan ED, Hughes J, Ferenbach DA. Renal aging: causes and consequences[J]. J Am Soc Nephrol, 2017, 28(2):407-420.
[61]
Saran R, Robinson B, Abbott KC, et al. US renal data system 2017 annual data report: epidemiology of kidney disease in the United States[J]. Am J Kidney Dis, 2018, 71(4):501.
[62]
Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI[J]. J Am Soc Nephrol, 2013, 24(1):37-42.
[63]
Minutolo R, Borrelli S, De Nicola L. CKD in the elderly: kidney senescence or blood pressure-related nephropathy?[J]. Am J Kidney Dis, 2015, 66(2):184-186.
[64]
Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey[J]. Lancet, 2012, 379(9818):815-822.
[65]
Tonelli M, Riella MC. World Kidney Day 2014: CKD and the aging population[J]. Am J Kidney Dis, 2014, 63(3):349-353.
[66]
Kitada K, Nakano D, Ohsaki H, et al. Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy[J]. J Diabet Complicat, 2014, 28(5):604-611.
[67]
Silva FG. The aging kidney: a review--partⅡ[J]. Int Urol Nephrol, 2005, 37(2):419-432.
[68]
Liu J, Yang JR, He YN, et al. Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy[J]. Transl Res, 2012, 159(6):454-463.
[69]
de Keizer PL. The fountain of youth by targeting senescent cells?[J]. Trend Molecul Med, 2017, 23(1):6-17.
[70]
Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging[J]. Cell, 2017, 169(1):132-147.
[71]
Moskalev A, Guvatova Z, Lopes IA, et al. Targeting aging mechanisms: pharmacological perspectives[J]. Trend Endocrinol Metabol, 2022, 33(4):266-280.
[72]
Madeo F, Tavernarakis N, Kroemer G. Can autophagy promote longevity?[J]. Nat Cell Biol, 2010, 12(9):842-846.
[73]
Hofer SJ, Daskalaki I, Bergmann M, et al. Spermidine is essential for fasting-mediated autophagy and longevity[J]. Nat Cell Biol, 2024, 26(9):1571-1584.
[74]
de Magalhães JP. Ageing as a software design flaw[J]. Genom biol, 2023, 24(1):51.
[75]
Michaloglou C, Vredeveld LC, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi[J]. Nature, 2005, 436(7051):720-724.
[76]
Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age[J]. Nat Med, 2018, 24(8):1246-1256.
[77]
Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs[J]. Aging Cell, 2015, 14(4):644-658.
[78]
Farr JN, Xu M, Weivoda MM, et al. Targeting cellular senescence prevents age-related bone loss in mice[J]. Nat Med, 2017, 23(9):1072-1079.
[79]
Ogrodnik M, Miwa S, Tchkonia T, et al. Cellular senescence drives age-dependent hepatic steatosis[J]. Nat Communicat, 2017, 8:15691.
[80]
Palmer AK, Xu M, Zhu Y, et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction[J]. Aging Cell, 2019, 18(3):e12950.
[81]
Zhang P, Kishimoto Y, Grammatikakis I, et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model[J]. Nat Neurosci, 2019, 22(5):719-728.
[82]
Schafer MJ, White TA, Iijima K, et al. Cellular senescence mediates fibrotic pulmonary disease[J]. Nat Communicat, 2017, 8:14532.
[83]
Kim SR, Puranik AS, Jiang K, et al. Progressive cellular senescence mediates renal dysfunction in ischemic nephropathy[J]. J Am Soc Nephrol, 2021, 32(8):1987-2004.
[1] 陈雅杰, 康鹏德. 滑膜细胞衰老在骨关节炎病理机制及靶向治疗的研究进展[J/OL]. 中华关节外科杂志(电子版), 2025, 19(04): 445-455.
[2] 阮希伦, 单臻, 范远键, 林颖, 王深明, 龙健婷, 徐向东. 一项妊娠相关性乳腺癌病理学特征、治疗方案及预后信息的回顾性研究[J/OL]. 中华普通外科学文献(电子版), 2025, 19(05): 340-344.
[3] 马文明, 梁朝朝. 肾脏肿瘤保留肾单位手术的技术进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(04): 404-411.
[4] 杨刚, 黄徐建, 朱建交, 熊永福, 李敬东. 两种不同类型肝门周围胆管癌临床病理特征及生存预后[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 931-938.
[5] 董艳, 郭继武, 毛杰. 儿童重症急性胰腺炎一例诊治分析并文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(06): 956-961.
[6] 乔晞. 肥胖相关性肾脏疾病的治疗[J/OL]. 中华肾病研究电子杂志, 2025, 14(05): 300-300.
[7] 曾锐. 抑制急性肾损伤向慢性肾脏病转化:靶向致病性肾脏巨噬细胞纳米药物的应用[J/OL]. 中华肾病研究电子杂志, 2025, 14(05): 241-247.
[8] 付梦珺, 杨淳淳, 魏丽敏, 赵雪, 蒋红利, 陈蕾. 成年人昼夜节律综合征与白蛋白尿的关联研究[J/OL]. 中华肾病研究电子杂志, 2025, 14(05): 264-269.
[9] 李鑫睿, 江明珠, 时萍, 牟洪宾. 线粒体稳态在慢性肾脏病发病机制中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2025, 14(05): 276-287.
[10] 李媛媛, 李荣山. 机器学习:肾脏疾病研究与诊疗的新前沿[J/OL]. 中华肾病研究电子杂志, 2025, 14(04): 181-187.
[11] 王柯云, 孙雅佳, 李甜, 张钰哲, 郑颖, 张伟光, 王倩, 董哲毅. 糖尿病肾脏疾病早期发生风险预测模型的研究进展[J/OL]. 中华肾病研究电子杂志, 2025, 14(04): 218-225.
[12] 崔少远, 傅博, 刘佳琦, 张双纳, 沈婉君, 宋泽龙, 朱晗玉. 小鼠肾脏透明荧光标本制备及光片荧光显微镜成像技能的教学分析[J/OL]. 中华肾病研究电子杂志, 2025, 14(04): 226-230.
[13] 梁爽, 崔敬, 王涌, 朱晗玉, 蔡广研. 思维导图结合案例教学在肾脏病学临床教学中的效果[J/OL]. 中华肾病研究电子杂志, 2025, 14(04): 231-235.
[14] 慕佳霖, 孙萌, 李育霖, 邹卉. 甲基丙二酸血症合并肾脏并发症的发生机制和治疗研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(05): 382-387.
[15] 唐梦楚, 段俗言, 王宁宁, 毛慧娟, 刘云. 胰高血糖素样肽-1受体激动剂应用于糖尿病肾脏疾病的进展更新[J/OL]. 中华临床医师杂志(电子版), 2025, 19(04): 307-314.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?