To target cellular senescence in diabetic kidney disease: the known and the unknown DOI Creative Commons

Yuehan Wei,

Shan Mou, Qing Yang

et al.

Clinical Science, Journal Year: 2024, Volume and Issue: 138(16), P. 991 - 1007

Published: Aug. 1, 2024

Abstract Cellular senescence represents a condition of irreversible cell cycle arrest, characterized by heightened senescence-associated beta-galactosidase (SA-β-Gal) activity, secretory phenotype (SASP), and activation the DNA damage response (DDR). Diabetic kidney disease (DKD) is significant contributor to end-stage renal (ESRD) globally, with ongoing unmet needs in terms current treatments. The role pathogenesis DKD has attracted substantial attention evidence premature this condition. process cellular appears be associated mitochondrial redox pathways, autophagy, endoplasmic reticulum (ER) stress. Increasing accumulation senescent cells diabetic not only leads an impaired capacity for repair injury, but also secretion pro-inflammatory profibrotic cytokines growth factors causing inflammation fibrosis. Current treatments diabetes exhibit varying degrees renoprotection, potentially via mitigation kidney. Targeting clearance through pharmaceutical interventions could emerge as promising strategy preventing treating DKD. In paper, we review understanding summarize possible therapeutic relevant field.

Language: Английский

VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis DOI

Pingcui Xu,

Bingfeng Lin,

Xuehui Deng

et al.

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 193, P. 720 - 735

Published: Nov. 1, 2022

Language: Английский

Citations

64
Ganoderic acid D prevents oxidative stress‐induced senescence by targeting 14‐3‐3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells DOI
Huan Yuan, Yan Xu, Yi Luo

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 21(9)

Published: Aug. 5, 2022

Abstract Stem cell senescence is an important cause of aging. Delaying may present a novel way to combat aging and age‐associated diseases. This study provided mechanistic insight into the protective effect ganoderic acid D (GA‐D) against human amniotic mesenchymal stem (hAMSCs) senescence. GA‐D, Ganoderma lucidum ‐derived triterpenoid, markedly prevented hAMSCs via activating Ca 2+ calmodulin (CaM)/CaM‐dependent protein kinase II (CaMKII)/nuclear erythroid 2‐related factor 2 (Nrf2) axis, 14‐3‐3ε was identified as target GA‐D. 14‐3‐3ε‐encoding gene ( YWHAE ) knockdown in reversed activation CaM/CaMKII/Nrf2 signals attenuate GA‐D anti‐aging increase senescence‐associated β ‐galactosidase (SA‐ ‐gal), p16 p21 expression levels, including reactive oxygen species (ROS) production, thereby promoting cycle arrest decreasing differentiation potential. overexpression maintained or slightly enhanced effect. d ‐galactose‐caused mice by significantly increasing total antioxidant capacity, well superoxide dismutase glutathione peroxidase activity, reducing formation malondialdehyde, advanced glycation end products, receptor products. Consistent with mechanism senescence, delayed bone‐marrow cells this model vivo, reduced SA‐ ‐gal ROS alleviated arrest, viability regulating axis. Therefore, retards targeting activate signaling pathway. Furthermore, vivo involve regulation same signal

Language: Английский

Citations

43
Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources DOI Creative Commons
Lili Song, Shicui Zhang

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1600 - 1600

Published: Oct. 31, 2023

Aging is a natural and inescapable phenomenon characterized by progressive deterioration of physiological functions, leading to increased vulnerability chronic diseases death. With economic medical development, the elderly population gradually increasing, which poses great burden society, economy field. Thus, healthy aging has now become common aspiration among people over world. Accumulating evidence indicates that substances can mediate deteriorated processes are highly likely have potential prolong lifespan improve aging-associated diseases. Foods from sources full bioactive compounds, such as polysaccharides, polyphenols, carotenoids, sterols, terpenoids vitamins. These compounds their derivatives been shown be able delay and/or diseases, thereby prolonging lifespan, via regulation various processes. Here, we summarize current understanding anti-aging activities vitamins food sources, modes action in delaying improving This will certainly provide reference for further research on effects sources.

Language: Английский

Citations

25
Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment DOI Creative Commons
Xiaoyu Zhang, Shaoqiu Leng, Xinyue Liu

et al.

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 3, 2024

Abstract Background Vasculopathy is the most common complication of diabetes. Endothelial cells located in innermost layer blood vessels are constantly affected by flow or vascular components; thus, their mechanosensitivity plays an important role mediating regulation. damage, one main causes hyperglycemic complications, has been extensively studied. However, mechanosensitive signaling endothelial damage remains unclear. Methods Vascular endothelial-specific Piezo1 knockout mice were generated to investigate effects on Streptozotocin-induced hyperglycemia and injury. In vitro activation knockdown was performed evaluate proliferation, migration, tubular function human umbilical vein high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, oxidative stress-related products used assess extent stress caused activation. Results Our study found that VE CreERT2 ;Piezo1 flox/flox with conditional cells, deficiency alleviated streptozotocin-induced reduced apoptosis abscission thoracic aortic decreased inflammatory response tissue Moreover, showed a thinner wall, tunica media increased nitric oxide synthase expression transgenic mice, indicating relief hyperglycemia. We also aggravated injury resulted severe dysfunction through Ca 2+ -induced CaMKII-Nrf2 axis cells. partially restored superoxide dismutase activity malondialdehyde content aorta. Mechanistically, CaMKII phosphorylation Nrf2 its downstream molecules HO-1 NQO1. Conclusion summary, our revealed involved glucose-induced dysfunction, which have great significance for alleviating

Language: Английский

Citations

9
Dietary Triterpenoids in Functional Food and Drug Ingredients: a review of structure-activity relationships, biosynthesis, applications, and AI-driven strategies DOI
Chao Fang, Haixia Yang, Daidi Fan

et al.

Trends in Food Science & Technology, Journal Year: 2025, Volume and Issue: unknown, P. 104961 - 104961

Published: March 1, 2025

Language: Английский

Citations

1
Hydrogen sulfide mitigates mitochondrial dysfunction and cellular senescence in diabetic patients: Potential therapeutic applications DOI

Ting Chen,

Dacheng Bai,

Changyong Gong

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 116556 - 116556

Published: Sept. 1, 2024

Language: Английский

Citations

7
Increased production and anti-senescence activity of exopolysaccharides in Ganoderma lingzhi by co-overexpression of β-1,3-glucan synthase and UDP-glucose pyrophosphorylase DOI

Yong-Liang Xu,

Huan Yuan, Na Li

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126778 - 126778

Published: Sept. 6, 2023

Language: Английский

Citations

14
14–3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer DOI Creative Commons
Yue Zhang,

Man Yan,

Yongjun Yu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 26, 2024

Abstract Over the past decade, role of 14–3-3 protein has received increasing interest. Seven subtypes proteins exhibit high homology; however, each subtype maintains its specificity. The 14–3-3ε is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cycle regulation, repolarization cardiac action, development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant development progression diseases, such as cardiovascular inflammatory neurodegenerative disorders, cancer. These immense involvements diverse processes makes it promising target for drug development. Although extensive research been conducted on dimers, studies monomers are limited. This review aimed to provide an overview recent reports molecular mechanisms regulation binding partners by 14–3-3ε, focusing issues that could help advance frontiers this field.

Language: Английский

Citations

6
Piezo1 alleviates acetaminophen-induced acute liver injury by activating Nrf2 and reducing mitochondrial reactive oxygen species DOI
Qimeng Wang,

Xuyun Peng,

Yifan Chen

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 652, P. 88 - 94

Published: Feb. 18, 2023

Language: Английский

Citations

13
Leucine zipper protein 1 prevents doxorubicin-induced cardiotoxicity in mice DOI Creative Commons
Di Fan,

Zhili Jin,

Jianlei Cao

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 64, P. 102780 - 102780

Published: June 18, 2023

Doxorubicin (DOX) is commonly used for chemotherapy; however, its clinical value extremely dampened because of the fatal cardiotoxicity. Leucine zipper protein 1 (LUZP1) plays critical roles in cardiovascular development, and this study designed determining function mechanism DOX-induced cardiotoxicity.Cardiac-specific Luzp1 knockout (cKO) transgenic (cTG) mice received a single or repeated DOX injections to establish acute chronic Biomarkers inflammation, oxidative damage cell apoptosis were evaluated. Transcriptome co-immunoprecipitation analysis screen underlying molecular pathways. Meanwhile, primary cardiomyocytes applied confirm beneficial effects LUZP1 depth.LUZP1 was upregulated DOX-injured hearts cardiomyocytes. Cardiac-specific deficiency aggravated, while cardiac-specific overexpression attenuated DOX-associated damage, cardiac injury. Mechanistic studies revealed that ameliorated cardiotoxicity through activating 5'-AMP-activated kinase (AMPK) pathway, AMPK abolished cardioprotection LUZP1. Further findings suggested interacted with phosphatase activate pathway. Moreover, we determined could also attenuate injury mice.LUZP1 attenuates ventricular impairment regulating gene therapy targeting may provide novel therapeutic approached treat

Language: Английский

Citations

13