Podocyte senescence: from molecular mechanisms to therapeutics

As an important component of the glomerular filtration membrane, the state of the podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of podocytes will allow...

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Main Authors: Qian Zhao, Yongzhang Huang, Ningying Fu, Caixia Cui, Xuan Peng, Haiyan Kang, Jie Xiao, Guibao Ke
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398712
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author Qian Zhao
Yongzhang Huang
Ningying Fu
Caixia Cui
Xuan Peng
Haiyan Kang
Jie Xiao
Guibao Ke
author_facet Qian Zhao
Yongzhang Huang
Ningying Fu
Caixia Cui
Xuan Peng
Haiyan Kang
Jie Xiao
Guibao Ke
author_sort Qian Zhao
collection DOAJ
description As an important component of the glomerular filtration membrane, the state of the podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of podocytes will allow us to understand their susceptibility to injury and identify targeted protective mechanisms. In fact, the process of physiological aging itself can induce podocyte senescence. Pathological stresses, such as oxidative stress, mitochondrial damage, secretion of senescence-associated secretory phenotype, reduced autophagy, oncogene activation, altered transcription factors, DNA damage response, and other factors, play a crucial role in inducing premature senescence and accelerating aging. Senescence-associated-β-galactosidase (SA-β-gal) is a marker of aging, and β-hydroxybutyric acid treatment can reduce SA-β-gal activity to alleviate cellular senescence and damage. In addition, CCAAT/enhancer-binding protein-α, transforming growth factor-β signaling, glycogen synthase kinase-3β, cycle-dependent kinase, programmed cell death protein 1, and plasminogen activator inhibitor-1 are closely related to aging. The absence or elevation of these factors can affect aging through different mechanisms. Podocyte injury is not an independent process, and injured podocytes interact with the surrounding epithelial cells or other kidney cells to mediate the injury or loss of podocytes. In this review, we discuss the manifestations, molecular mechanisms, biomarkers, and therapeutic drugs for podocyte senescence. We included elamipretide, lithium, calorie restriction, rapamycin; and emerging treatment strategies, such as gene and immune therapies. More importantly, we summarize how podocyte interact with other kidney cells.
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spelling doaj-art-ef71fad370d84b5e9a0202dd2b1ffcc22025-08-20T03:05:26ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2398712Podocyte senescence: from molecular mechanisms to therapeuticsQian Zhao0Yongzhang Huang1Ningying Fu2Caixia Cui3Xuan Peng4Haiyan Kang5Jie Xiao6Guibao Ke7Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Nephrology, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaAs an important component of the glomerular filtration membrane, the state of the podocytes is closely related to kidney function, they are also key cells involved in aging and play a central role in the damage caused by renal aging. Therefore, understanding the aging process of podocytes will allow us to understand their susceptibility to injury and identify targeted protective mechanisms. In fact, the process of physiological aging itself can induce podocyte senescence. Pathological stresses, such as oxidative stress, mitochondrial damage, secretion of senescence-associated secretory phenotype, reduced autophagy, oncogene activation, altered transcription factors, DNA damage response, and other factors, play a crucial role in inducing premature senescence and accelerating aging. Senescence-associated-β-galactosidase (SA-β-gal) is a marker of aging, and β-hydroxybutyric acid treatment can reduce SA-β-gal activity to alleviate cellular senescence and damage. In addition, CCAAT/enhancer-binding protein-α, transforming growth factor-β signaling, glycogen synthase kinase-3β, cycle-dependent kinase, programmed cell death protein 1, and plasminogen activator inhibitor-1 are closely related to aging. The absence or elevation of these factors can affect aging through different mechanisms. Podocyte injury is not an independent process, and injured podocytes interact with the surrounding epithelial cells or other kidney cells to mediate the injury or loss of podocytes. In this review, we discuss the manifestations, molecular mechanisms, biomarkers, and therapeutic drugs for podocyte senescence. We included elamipretide, lithium, calorie restriction, rapamycin; and emerging treatment strategies, such as gene and immune therapies. More importantly, we summarize how podocyte interact with other kidney cells.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398712Podocyte senescencemolecular mechanismsbiomarkersintervention targets
spellingShingle Qian Zhao
Yongzhang Huang
Ningying Fu
Caixia Cui
Xuan Peng
Haiyan Kang
Jie Xiao
Guibao Ke
Podocyte senescence: from molecular mechanisms to therapeutics
Renal Failure
Podocyte senescence
molecular mechanisms
biomarkers
intervention targets
title Podocyte senescence: from molecular mechanisms to therapeutics
title_full Podocyte senescence: from molecular mechanisms to therapeutics
title_fullStr Podocyte senescence: from molecular mechanisms to therapeutics
title_full_unstemmed Podocyte senescence: from molecular mechanisms to therapeutics
title_short Podocyte senescence: from molecular mechanisms to therapeutics
title_sort podocyte senescence from molecular mechanisms to therapeutics
topic Podocyte senescence
molecular mechanisms
biomarkers
intervention targets
url https://www.tandfonline.com/doi/10.1080/0886022X.2024.2398712
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AT xuanpeng podocytesenescencefrommolecularmechanismstotherapeutics
AT haiyankang podocytesenescencefrommolecularmechanismstotherapeutics
AT jiexiao podocytesenescencefrommolecularmechanismstotherapeutics
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