MECHANISMS OF AGEING AND DEVELOPMENT
·
2024
·
IF 5.3
Zhen-Zhen Yu,Jia-Jun Tu,Mei-Ling Ou,Jin-Xiong Cen,Kun Xue,Shao-Jun Li,Jing Zhou,Guo-Dong Lu
Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans , demonstrating a intriguing “elixir in youth, poison in elder” phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57 , a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans , and C46G7.1 , unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1 / nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.
研究领域:
药理学
·
老年学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 51
·32898-32902
·
IF 4.036
Fanwei Meng,Guofang Ma,Jiahe Qiu,Zhendong Fu,Jiaqing Yan,Lingping Wang
Nanozyme is a material with enzyme-like catalytic activity, which has been widely used in environmental, antibacterial, and other fields of research. However, there are few reports on the toxicity of nanozymes. In this work, nanozymes co-assembled from sodium N-lauroyl sarcosinate (Ls) and Cu ions possess a Cu(I)–Cu(II) electron transfer system similar to that of natural laccases. Reaction kinetic studies show that the catalyst follows a typical Michaelis–Menten model. Cu–N-lauroyl sarcosinate nanozyme (Cu-Ls NZ) possess excellent laccase-like activity to oxidize a variety of phenol-containing substrates, such as phenol, 4-iodophenol, and 2,4,5-trichlorophenol. To evaluate the toxicity of the material, the nematode C. elegans was exposed to various concentrations of Cu-Ls NZ. Effects on physiological levels were determined. The results showed that high doses of Cu-Ls NZ increased the amount of reactive oxygen species (ROS), decreased the locomotor activity of nematodes, and inhibited their larval growth.
研究领域:
纳米技术
·
生物化学
·
毒理学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2018
·
IF 4.483
Siyu Wu,Lili Lei,Yang Song,Mengting Liu,Shibo Lu,Dan Lou,Yonghong Shi,Zhibin Wang,Defu He
Mitochondrial dysfunction is considered as a critical mechanism in the pathogenesis of Parkinson's disease (PD). Increasing evidence supports the notion of mitochondria-associated membranes (MAMs) in mitochondrial dysfunction; yet little is known about the role of MAMs-related proteins in the pathogenesis of PD. Herein we exposed the nematode Caenorhabditis elegans to 0.5–10.0 μM rotenone (RO) or 0.2–1.6 mM paraquat (PQ) for 3 days. Our results showed that both RO and PQ induced similar Parkinsonism including motor deficits and dopaminergic degeneration. RO/PQ caused mitochondrial damages characterized by the increase of vacuole areas and autophagy vesicles, but the decrease of mitochondrial cristae. RO/PQ-impacted mitochondrial function was also demonstrated by the decrease of ATP level and mitochondrial membrane potential . Additionally, the attachment or surrounding of endoplasmic reticulum to the damaged mitochondria indicates ultrastructural alterations in MAMs. Using fluorescently labeled transgenic nematodes, we further found that the expression of tomm-7 and genes of Complex I, II and III was reduced, whereas the expression of pink-1 was increased in the exposed animals. To determine MAMs in toxicity toward PD, we investigated the mutants of hop-1 and pink-1 , encoding presenilin and PTEN-induced putative kinase 1 (PINK1) in mitochondria-associated membranes, respectively. Results demonstrated that the mutation of both hop-1 and pink-1 reduced the vulnerability of lethal, behavioral, and mitochondrial toxicity induced by RO/PQ. These findings suggest that presenilin and PINK1 play important roles in the RO/PQ-induced neurotoxicity through the mechanisms involved in mitochondria-associated membranes.
研究领域:
神经生物学
·
分子生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2017
·Vol. 42
·期 11
·3061-3072
·
IF 2.581
He Qidi,Huang Guan,Chen Yixin,Wang Xiaoqin,Huang Zhishu,Chen Zuanguang
Cerebral deposition of amyloid β-peptide (Aβ), a fundamental feature of Alzheimer’s disease (AD), damages the neurocytes and impairs the cognition functions and associative learning memory of AD patients. A series of novel 2-arylethenylquinoline derivatives were synthesized and evaluated in our previous study, which inhibited Aβ aggregation in vitro effectively at the concentration of 20 μmol/L and exhibited high antioxidant activity. In order to verify the capacity of anti-AD in vivo, the transgenic Caenorhabditis elegans ( C. elegans ) strain CL2355 expressing neural Aβ was employed as the AD model to investigate the neuroprotective activity of seven high-potential compounds (4a1, 4a2, 4b1, 4b2, 4c1, 4c2, 4c3) selected from those derivatives. Learning memory associated chemotaxis assay was performed to evaluate the neural repairment capacity. The underlying mechanism was investigated by mRNA analysis of Aβ gene and heat shock protein genes ( hsp-16.1 and hsp-16.2 ) and Western blot of Aβ. Our data indicated that among seven tested compound, 4b1 and 4c2 reduced Aβ-induced stress, suppressed the expression of neural Aβ monomers and toxic oligomers, and recovered the damaged associative learning memory in C. elegans AD model. These findings further confirmed their potentials to become valuable agents for AD therapy.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Zhishen Xie,Jianping Zhao,Hui Wang,Yali Jiang,Qiaoling Yang,Yu Fu,Huahui Zeng,Christian Hölscher,Jiangyan Xu,Zhenqiang Zhang
This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans . More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effects were also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 5
·
IF 5.6
Tong Chen,Jing Zhang,Shaoqin Jian,Bocen Chen,Yingjie Ma,Wenguang Wang,Tianpeng Ma,Jiran Shi,Jin Yang,Man Xiao
Paederia scandens(Lour.)Merris a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects ofpaederoside(PSG) have not been thoroughly investigated; therefore, in this study,Caenorhabditis elegans(C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan ofC. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant geneskn-1and longevity-associated genedaf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited inC. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component ofPaederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feedingC. elegansPSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.
✓ 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）