PHYTOMEDICINE
·
2024
·
IF 6.7
Wentao Sun,Yue Gao,Yubing Wu,Wei Wu,Chaofan Wang,JiaXiao Chen,Changjiao Luan,Ming Hua,Weili Liu,Weijuan Gong,Xingjie Ma
Background Accumulation of senescent cells in tissues and their downstream effect programs have emerged as key drivers of aging and age-associated pathologies. Recent progresses in senotherapeutics indicated that either selectively killing senescent cells with senolytics or suppressing the senescence-associated secretory phenotype (SASP) secretion using senomorphics contributes to extending of the healthy lifespan and alleviating numerous age-related disorders in mice. Purpose However, the potential side-effects and long-term cytotoxicity of the above novel compounds have not yet been determined. Therefore, it seems to be more efficient to explore new senotherapeutical functions from approved drugs. Methods The effects of valproic acid (VPA), a derivative of valine, in cellular senescence were evaluated by senescence-associated β galactosidase (SA-β-Gal) staining, flow cytometry and western blot (WB). The cell viability was tested using CCK-8 kits. Cell apoptosis was detected by Annexin V-EGFP/PI apoptosis detection kit. Cell autophagy was checked using GFP-RFP-LC3 ratiometric plasmid. The roles of VPA in lung aging were investigated by in vivo experiments using H&E and Masson staining, WB, as well as electronic microscope strategies. Results Here we identified VPA was able to induce an over-accumulation of reactive oxygen species (ROS) (>1.5 times increasing) and apoptosis (>2 times increasing) of senescent cells. Mechanistically, VPA activated the phospholipid modifying enzyme membrane-bound O-acyltransferase domain-containing protein 1 (MBOAT1), which was repressed during senescence, then promoted mitochondrial autophagy and apoptosis. In addition, VPA was also found to alleviate therapy induced abnormal mitochondria and lung aging phenotype (>1.5 times decreasing of lung fibrosis markers and >2.5 times increasing of naïve/memory CD4+ or CD8+ cells) in vivo . Conclusion Taken together, our study demonstrated that VPA was able to selectively killing senescent cells both in vitro and in vivo , and thus shedding light on new functions and novel potential application of VPA in anti-aging and anti-age-associated diseases.
研究领域:
衰老
·
药理学
·
细胞生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-13
·
IF 17.694
Sun Jie,Wang Ming,Zhong Yaqi,Ma Xuan,Sun Shimin,Xu Chenzhong,Peng Linyuan,Li Guo,Zhang Liting,Liu Zuojun,Ai Ding,Liu Baohua
The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1 +/m ‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1 +/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.
研究领域:
衰老
·
分子生物学
·
遗传学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Wei Wei,Xiaobing Ren,Fan Yi,Xuhui Zhang,Jiali Hou,Zhenxing Zhang,Liqian Yuan,Li Li,Qi Gao
Plant exosomes, small vesicles released by plant cells that contain various bioactive molecules, have garnered great attention for their potential applications in medicine, yet their delivery applications for skincare remain underexploited. Resveratrol (RES), renowned for its remarkable antiaging properties, faces challenges in transdermal absorption due to the stratum corneum barrier, hindering its efficacy. To address this, we developed a delivery system incorporating RES-loaded plant (Leontopodium alpinum) exosome (LEOEXO@RES). Evaluation through both in vitro and in vivo experiments demonstrated LEOEXO@RES’s enhanced delivery of bioactive compounds and multifaceted skincare impact. Specifically, this approach not only promoted environmentally responsible waste reuse but also achieved harmonious synergy between LEOEXO carriers and RES, enhancing their overall efficacy. The LEOEXO@RES effectively ameliorated inflammation levels and inhibited cellular senescence, highlighting its promising potential in antiaging skincare applications.
研究领域:
生物学
·
医学
·
皮肤科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Chengjin Ding,Jiao Min,Yongkang Tan,Liuting Zheng,Ruxuan Ma,Ruyi Zhao,Huiyue Zhao,Qingqing Ding,Hongshan Chen,Da Huo
Senescence plays a critical role in the development and progression of various diseases. This study introduces an amorphous, high-entropy alloy nanozyme-based therapeutic designed to combat senescence. We start by screening ligands to optimize the synthesis of the amorphous nanozyme. By adjusting the nanozyme's composition and surface properties, we analyze its catalytic performance under both normal and aging conditions, confirming that peroxide and superoxide dismutase activity are crucial for its anti-aging therapeutic function. Subsequently, we validate the chiral-dependent therapeutic effects and demonstrate the senolytic performance of D-handed PtPd2CuFe across several aging models. Through proteomic and transcriptome analyses, we explore the mechanism underlying the senolytic action exerted by nanozyme in depth. We confirm that exposure to senescent conditions led to the enrichment of copper and iron atoms in the nanozyme's lower oxidation states, disrupting the iron-thiol cluster in mitochondria and lipoic acid transferase, as well as oxidizing unsaturated fatty acids. These actions triggered a cascade of cuproptotic and ferroptotic cell death. Additionally, we found that the nanozyme's anti-aging effects depend on concentration. Even an ultra-low dose of the therapeutic can act as a senomorphic, reducing the effects of senescence. Given its broad-spectrum action and concentration-adjustable anti-aging potential, we confirmed the remarkable therapeutic capability of D-handed PtPd2CuFe in managing atherosclerosis, a disease involving various types of senescent cells. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
药学
·
老年学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Qian Yuan,Yuting Zhu,Ben Tang,Yaru Xie,Mingcun Hu,Hua Su,Youhua Liu,Chun Zhang
Cellular senescence is a hallmark of aging and the accumulation of senescent cells (SnCs) accelerates the aging process, contributing to aging-related organ disorders. The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, this work demonstrates that PRDM16, a member of the PRDM protein family, decreases significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging-related organ injury. Furthermore, tubular-specific Prdm16 deletion aggravates irradiation-induced kidney aging and aging-related kidney diseases in irradiated mice subjected to ischemia-reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulates the transcription of glutathione S-transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reverses PRDM16 deficiency-induced cellular senescence and kidney aging. Collectively, these results provide a potential target for the investigation of anti-aging therapies.
研究领域:
分子生物学
·
老年学
·
肾脏病学
·
氧化应激
·
遗传学
·
转化医学
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Abdelmoaty Ahmed Attia Ahmed,Chen Jing,Zhang Kun,Wu Changhui,Li Ye,Li Peng,Xu Jianhua
Background: Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.Methods: In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.Results: We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR.Conclusion: A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AGING CELL
·
2024
·
IF 8
Xueling He,Chen Wang,Qianyu Zhang,Tong Yang,Qiuyan Guo,Yaxu Wang,Jiayue Guo,Pengjie Wang,Junzhe Zhang,Huan Tang,Yinhua Zhu,Jigang Wang
Cellular senescence plays a critical role in repeated ultraviolet (UV) exposure-induced skin photoaging. Currently, from the perspective of regulating senescent cells, potent compounds or reliable protein targets that could effectively prevent skin photoaging have not yet been reported. Herein, we demonstrated that chlorogenic acid (CGA) significantly inhibited UVA-induced senescence of human dermis skin fibroblasts (HDF) cells by screening the natural product library. The activity-based protein profiling (ABPP) result revealed that Enolase 1 (ENO1) is one of the direct targets of CGA in HDF cells. Further mechanism research indicated that CGA covalently binds to ENO1, and prevented UVA-induced cellular senescence by suppressing the activity of ENO1 protein to block the glycolytic pathway. Importantly, we found that CGA dose-dependently reduced the skin wrinkle score, alleviated skin pathological features and inhibited senescent characteristics in a photoaging mouse model. The proteomic analysis revealed that CGA treatment effectively inhibited senescence-associated secretory phenotype (SASP) secretion and glycolysis in skin samples of mice. Collectively, our study not only demonstrated that inhibiting cell senescence is an effective anti-skin photoaging strategy, but also revealed that ENO1 is a promising protein target to prevent photoaging.
研究领域:
药理学
·
皮肤病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 14
·7560-7571
·
IF 6.317
Shuai Lu,Jinyi Zhou,Chen Yang,Xiaoxue Zhang,Yingying Shi,Jie Liu,Xintong Yan,Juanjuan Liang,Xianli Liu,Lan Luo,Da Zhou,Zhimin Yin
Aging is a natural process accompanied by inflammation and oxidative stress and is closely associated with age-related diseases. As a direct precursor of glutathione, γ-glutamylcysteine (γ-GC) possesses antioxidant and anti-inflammatory properties; however, whether γ-GC plays an important role in anti-aging remains unknown. Here, we investigated the protective effects and mechanisms of γ-GC in D-galactose (D-gal)-induced senescence in PC12 cells and aging mice. Our results showed that γ-GC treatment significantly reduced the percentage of senescence-associated-β-galactosidase (SA-β-Gal)-positive cells and inhibited D-gal-induced cell cycle arrest in PC12 cells. The results of Nissl and hematoxylin and eosin (H&E) staining in mouse brain showed that γ-GC treatment markedly reversed the damage in the hippocampus of D-gal-induced aging mice. Moreover, γ-GC increased the phosphorylation of AMP-activated protein kinase (AMPK) to promote the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) while inhibiting the nuclear translocation of deleted in breast cancer 1 (DBC1), which leads to the activation of sirtuin 1 (SIRT1) and deacetylation of p53 in the nucleus. Therefore, γ-GC may be a potential therapeutic candidate compound for the prevention and treatment of age-related diseases.
研究领域:
药理学
·
衰老
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GeroScience
·
2024
·
IF 5.3
Tang Qi,Xing Xiaotao,Huang Haisen,Yang Jian,Li Maojiao,Xu Xun,Gao Xin,Liang Cheng,Tian Weidong,Liao Li
Cellular senescence is an important risk factor in the development of hepatic steatosis. Senolytics present therapeutic effects on age-related hepatic steatosis without eliminating senescent hepatocytes directly. Therefore, it highlights the need to find senolytics’ therapeutic targets. Dysfunction of adipose tissue underlies the critical pathogenesis of lipotoxicity in the liver. However, the correlation between adipose tissue and hepatic steatosis during aging and its underlying molecular mechanism remains poorly understood. We explored the correlation between white adipose tissue (WAT) and the liver during aging and evaluated the effect of lipolysis of aged WAT on hepatic steatosis and hepatocyte senescence. We screened out the ideal senolytics for WAT and developed a WAT-targeted delivery system for senotherapy. We assessed senescence and lipolysis of WAT and hepatic lipid accumulation after treatment. The results displayed that aging accelerated cellular senescence and facilitated lipolysis of WAT. Free fatty acids (FFAs) generated by WAT during aging enhanced hepatic steatosis and induced hepatocyte senescence. The combined usage of dasatinib and quercetin was screened out as the ideal senolytics to eliminate senescent cells in WAT. To minimize non-specific distribution and enhance the effectiveness of senolytics, liposomes decorated with WAT affinity peptide P3 were constructed for senotherapy in vivo. In vivo study, WAT-targeted treatment eliminated senescent cells in WAT and reduced lipolysis, resulting in the alleviation of hepatic lipid accumulation and hepatocyte senescence when compared to non-targeted treatment, providing a novel tissue-targeted, effective and safe senotherapy for age-related hepatic steatosis.
研究领域:
老年学
·
药理学
·
代谢
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fugang Liu,Jiaqing Liu,Yang Luo,Siyi Wu,Xu Liu,Haoran Chen,Zhewen Luo,Haitao Yuan,Feng Shen,Fangfang Zhu,Jian Ye
Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated β-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H 2 O 2 . Overall, a novel SlipChip-SERS system is developed for single-cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing-related diseases.
研究领域:
生物技术
·
细胞生物学
·
老年学
·
代谢组学
·
微流控技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2025
·Vol. 82
·期 1
·1-15
·
IF 6.2
Guan Yiting,Deng Shuyue,Zou Xiaopeng,Wei Wenlu,Li Zechen,Zhong Jiajing,Zhu Yanmei,Zhang Donghui,Ju Yanmin,Sun Qing-Yuan,Zhang Hongyong
Low-quality oocytes directly affect fertilization and embryonic development, contributing to infertility in women, while germ cell senescence leads to reduced germ cell numbers and decreased egg quality. Dasatinib and quercetin (D and Q), as senolytic drugs, have been extensively explored in different age-related diseases. However, their effects on in vitro cultured senescent oocytes and the molecular mechanisms underpinning ovarian aging remain elusive. Here, we report that a nano-encapsulated senolytic D + Q cocktail efficiently improves the quality of post-ovulatory aging oocyte in vitro and follicle quantity in ovaries in a cyclophosphamide (Cy)-induced premature ovarian failure (POF) mouse model. Cocktail supplementation to cultured oocytes potently reduces reactive oxygen species (ROS) levels, maintains spindle integrity, decreases fragmented oocyte frequencies, rescues mislocalized cortical granules (CGs) and mitochondrial membrane potential (MMP), and alleviates DNA damage and apoptosis. Importantly, the cocktail effectively ameliorates fertility deficits in the model. Transcriptome analysis shows cocktail administration to fertility-deficient mice not only up-regulates developmental gene expression but also reduces senescence-associated secretory phenotype (SASP) accumulation. Therefore, our nano-encapsulated D + Q cocktail is a promising reagent for assisted reproductive technology and improving reproductive outcomes in POF. Graphical
研究领域:
生殖生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Lu-Yao Zheng,Yan-Xin Da,Xiu Luo,Xiao Zhang,Zhi-Jie Sun,De-Li Dong
Sorafenib is a targeted anticancer drug in clinic. Low-dose sorafenib has been reported to activate AMPK through inducing mitochondrial uncoupling without detectable toxicities. AMPK activation has been the approach for extending lifespan, therefore, we investigated the effect of sorafenib on lifespan and physical activity of C. elegans and the underlying mechanisms. In the present study, we found that the effect of sorafenib on C. elegans lifespan was typically hermetic. Sorafenib treatment at higher concentrations (100 μM) was toxic but at lower concentrations (1, 2.5, 5 μM) was beneficial to C. elegans . Sorafenib (1 μM) treatment for whole-life period extended C. elegans lifespan and improved C. elegans physical activity as manifested by increasing pharyngeal pumping and body movement, preserving intestinal barrier integrity, muscle fibers organization and mitochondrial morphology. In addition, sorafenib (1 μM) treatment enhanced C. elegans stress resistance. Sorafenib activated AMPK through inducing mitochondrial uncoupling in C. elegans . Sorafenib treatment activated DAF-16, SKN-1, and increased SOD-3, HSP-16.2, GST-4 expression in C. elegans . Sorafenib treatment induced AMPK-dependent autophagy in C. elegans . We conclude that low-dose sorafenib protects C. elegans against aging through activating AMPK/DAF-16 dependent anti-oxidant pathways and stimulating autophagy responses. Low-dose sorafenib could be a strategy for treating aging and aging-related diseases.
研究领域:
药理学
·
老年学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）