JOURNAL OF BIOLOGICAL CHEMISTRY
·
2013
·Vol. 288
·期 50
·35671-35682
·
IF 4.651
Jie Li,Ke Yao,Xiaoning Yu,Xinran Dong,Lishe Gan,Chenqi Luo,Yalin Wu
Lipofuscin accumulation in retinal pigment epithelial (RPE) cells of the eye implicates the etiologies of Stargardt disease and age-related macular degeneration, a leading cause of blindness in the elderly. Here, we have identified a previously unknown RPE lipofuscin component. By one- and two-dimensional NMR techniques and mass spectrometry, we confirmed that this compound is a new type of pyridinium bisretinoid presenting an unusual structure, in which two polyenic side chains are attached to adjacent carbons of a pyridinium ring. This pigment is a light-induced isomer of isoA2E, rather than A2E, referred to as iisoA2E. This pigment is a fluorescent lipofuscin compound with absorbance maxima at ∼430 and 352 nm detected in human, pig, mouse, and bovine eyes. Formation of iisoA2E was found in reaction mixtures of all-trans-retinal and ethanolamine. Excess intracellular accumulation of this adduct in RPE cells in vitro leads to a significant loss of cell viability and caused membrane damage. Phospholipase D-mediated phosphodiester cleavage of the A2PE series generated isoA2E and iisoA2E, in addition to A2E, thus corroborating the presence of isoA2PE and iisoA2PE that may serve as biosynthetic precursors of isoA2E and iisoA2E.
研究领域:
眼科学
·
生物化学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xinxin Fan,Yu Lu,Yujun Xie,Xiaodong Yan,Wanyu Fan,Yuji Ishii,Boyang Yu,Renshi Li
Anemarrhena asphodeloides Bge. (AAB), a traditional medicinal herb, has a long history of delaying the aging process. Yet, the anti-aging effects of its polysaccharides have not been thoroughly investigated. This study marks the first exploration of the anti-aging activity of Anemarrhena asphodeloides Bge. polysaccharides (AABP). The MW of AABP-1a was determined to be 210.062 kDa, with a composition consisting predominantly of glucose and mannose in a molar ratio of approximately 4:1. The backbone of AABP-1a was mainly composed of →4)-2Ac-β-Man(1→ and →4)-β-Glc(1→ and a small amount of branched →4,6)-β-Glc(1→ and →3,4)-β-Glc(1→, the branching part was composed of →6)-β-Glc(1→ and t-α-Glc(1→. AABP-1a has antioxidant capacity and can improve cell cycle arrest mediated by senescence markers such as p53 , p21 , p16 and SASP, and reduce the accumulation of damaged DNA. In addition, it could reduce the activity of SA- β -Gal in zebrafish, prolong the lifespan of C. elegans and reduce the expression of lipofuscin. This study found a glucomannan and demonstrated its anti-aging activity in various aging models. These results provide a theoretical basis for further study of the anti-aging effect of AAB.
研究领域:
中药学
·
生物化学
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2019
·
IF 3.579
Mohan Zhang,Xin Yang,Wan Xu,Xiaobo Cai,Mingxiang Wang,Yuying Xu,Peilin Yu,Jun Zhang,Yifan Zheng,Jiang Chen,Jun Yang,Xinqiang Zhu
High sugar content in beverage or food can affect the aging process, and thus natural/artificial sweeteners are widely used as substitutes. However, whether sweeteners have such adverse effects as sugar remains to be clarified. Therefore, in the current study, three sulfa sweeteners, namely, saccharin sodium salt hydrate (SAC 2 ), sodium cyclamate (CYC 3 ) and acesulfame potassium (AceK 4 ) were evaluated for their effects on the lifespan, deposition of lipofuscin, exercise activity, food intake, and intestinal fat deposition (IFD 5 ) of Caenorhabditis elegans ( C. elegans 6 ). It was shown that SAC at 0.3 and 10 mg/mL shortened the lifespan of C. elegans and impaired the exercise capacity, while at other concentrations no significant effects were observed. In contrast, CYC at 0.1, 1 and 10 mg/mL prolonged the lifespan of C. elegans. On the other hand, AceK at 1 mg/mL increased the lifespan of C. elegans , and could decrease both lipofuscin deposition and IFD in a dose-dependent manner. Taken together, these results indicated that although SAC, CYC, and AceK all belong to the sulfa sweeteners, each has distinct effects on different physiological activities associated with aging, at least in C. elegans .
研究领域:
生物化学
·
衰老研究
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 5
·1-20
·
IF 4
Chen Junlong,Long Yiqing,Zhou Xiaozeliang,Yin Zongning
This study aims to develop a multifunctional polymer nanovesicle system, AG86-β-glucan-poly(methionine-b-carboxybetaine) (AGPMC), which integrates AG86 peptide (a targeting ligand for the α6β4 integrin on basal keratinocytes) and reactive oxygen species (ROS) responsiveness to enhance the transdermal delivery of ergothioneine (EGT). The objective is to overcome the limitations of hydrophilic drug delivery and provide a targeted, ROS-triggered strategy for treating skin lipofuscin. AGPMC was synthesized via RAFT and ROP polymerization and self-assembles into stable nanovesicles (ANVs). Physicochemical characterization confirmed that the unloaded ANVs have an average size of 106.17 ± 3.26 nm and a polydispersity index (PDI) of 0.261 ± 0.027, with excellent stability and clear ROS-triggered structural responsiveness. After EGT loading, the nanovesicles exhibited a size of 140.10 ± 3.33 nm and a PDI of 0.217 ± 0.008. In vitro studies using HaCaT cells demonstrated a significant enhancement in cellular uptake, with an increase of up to 2.2-fold compared to free FSS ( p < 0.0001), as well as effective ROS scavenging and minimal cytotoxicity. The endocytosis mechanism study revealed that ANVs are primarily taken up via energy-dependent active transport, with caveolae-mediated endocytosis being the main pathway. Moreover, transdermal delivery studies confirmed that EGT-loaded nanovesicles significantly improved drug penetration through the stratum corneum. This work represents the first application of the AG86-conjugated nanovesicles for keratinocyte-targeted delivery, combined with ROS responsiveness. The “Loading-Targeting-Responding “ strategy holds significant potential for enhancing hydrophilic drug delivery and offers a promising approach for treating age-related skin lipofuscin accumulation. Graphical Targeted delivery of EGT via the “Loading-Targeting-Responding” strategy.
研究领域:
药剂学
·
皮肤病学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 106
·期 6
·e70214
·
IF 3.3
Guihua Jia,Jiayi Li,Abbas Khan,Aman Chandra Kaushik,Diyi Wu,Hongyu Chen,Rongpei Li,Jian Wang,Chen Zhang,Adil Farooq,Xueying Mao,Aamir Mehmood,Weidong Zhang,Heng Wang,Dong-Qing Wei
WGX-50, a previously reported drug candidate for Alzheimer's disease, is derived from Zanthoxylum bungeanum Maxim commonly called Sichuan pepper. Its pharmacological actions for the long run benefit of human health have been extensively investigated. However, in terms of its anti-aging effect, it totally remains unexplored. In this work, WGX-50 was first reported to promote healthy aging in Caenorhabditis elegans with insights from drug target prediction and molecular dynamics simulations. Further investigations have experimentally demonstrated that: Firstly, both daf-16 and skn-1 genes are causative to WGX-50 mediated longevity. WGX-50 failed to extend lifespan upon depletion of these genes in transgenic worms. Their orthologs Foxo1 and Nrf2 were also activated even in D-galactose (D-gal) induced aging and Zmpste24 −/− progeria mice intestines. Secondly, WGX-50 inhibits IIS signaling via downregulating daf-2 , and activating daf-16 and skn-1 genes, which thus enable downstream pro-longevity effectors increasing stress resistance and promoting healthier aging. WGX-50 increased expression levels of sod-3 , ctl-1 , gst-7/8/12/33 , gsto-1 , and heat shock protein genes such as hsp-12.2 , hsp-90 , F44E5.4/0.5 , T05E11.9 and their inducer hsf-1 . In addition, the accumulation of lipofuscin, fat, and reactive oxygen species levels with age was decreased significantly upon WGX-50 supplementation without physiological impairments. Thirdly, in progeria, D-gal and naturally aged mice, WGX-50 is incapable of inducing aging. Senescent genes and SASP factors were not produced at higher levels in livers and small intensities. No impact was observed on key organ indices, blood biochemistry parameters, and bone histomorphometry. WGX-50 perhaps prolongs lifespan through other mechanisms such as reducing fertility, inducing dietary restriction, and improving proteostasis with lowered levels of polyQ35 aggregates. Our findings thus provide primary insights for the potential medical use of WGX-50 in anti-aging and long-term healthcare.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOGERONTOLOGY
·
2025
·Vol. 26
·期 5
·1-24
·
IF 4.1
Chen Wendi,Liu Shuang,Xu Guoqiang,Liu Xin,Shi Yuxuan,Wang Guolong,Ning Yunna,Lu Zhiming,Cao Yongzhi,Zhao Yueran
Zuogui pill (ZGP) and Yougui pill (YGP) are classical kidney-tonifying formulas in Traditional Chinese Medicine, widely used clinically but with their potential to delay ageing and improve ageing biomarkers remaining unclear. This study combined network pharmacology and Caenorhabditis elegans models to investigate the anti-ageing effects and mechanisms of ZGP and YGP. Both formulas significantly extended lifespan (ZGP dose-dependently at 5–20 mg/mL; YGP at 20 mg/mL) and improved ageing biomarkers, as evidenced by enhanced motility, reduced lipofuscin accumulation and endogenous ROS levels, and increased resistance to heat and oxidative stress. Network analysis identified quercetin and kaempferol as the top-ranked shared active components. Subsequent experimental validation demonstrated that kaempferol (0.05–0.2 mM) replicated these pro-longevity effects and was shown to act by inducing mitophagy: it triggered an initial decrease followed by a long-term increase in mitochondrial content, concomitant with upregulated expression of mitophagy genes. Crucially, the lifespan-extending effects of kaempferol, ZGP, and YGP were completely abolished in bec-1 and pink-1 null mutants. This study establishes that ZGP and YGP delay ageing and improve ageing biomarkers in C. elegans by activating BEC-1/PINK-1-dependent mitophagy. Kaempferol was identified as a major active component mediating this effect, highlighting a key mechanism for the pro-longevity properties of these traditional formulas.
研究领域:
中医
·
药理学
·
衰老研究
·
分子生物学
·
线粒体生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Junpeng Zeng,Yu Song,Xiaowei Fan,Yanjun Liu,Peixu Cong,Xiaoming Jiang,Jie Xu,Changhu Xue
The present study evaluated lipid-involved browning mechanism during the drying process of squid. Initially, different lipid-Maillard reaction (MR) models were conducted based on the composition of squid (lipids, reducing sugars and amino acids). The degree of MR as well as α-dicarbonyl compounds (α-DCs) and lipid oxidation-mediated browning products (pyrroles and lipofuscin-like pigments) were detected. The results indicated that arginine and ribose were blamed for the browning of dried squid. Moreover, lipid oxidation provided glyoxal and methylglyoxal to participate in MR, and long-time heating and salting produced more α-DCs and accelerated browning. Meanwhile, dried squid contained hydrophobic pyrrole (17.45 μg/g lipid) and hydrophilic pyrrole (113.00 μg/g lipid), and the content of lipofuscin-like pigments increased by 1.5-fold after drying. Finally, defatting treatment demonstrated that the browning of dried squid was moderately alleviated by fat removal ( L* ↑, a* ↓ and b* ↓). These findings offer a novel perspective on moderately preventing the browning of dried aquatic products.
研究领域:
食品科学
·
化学
·
农业工程
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 6
·3313-3320
·
IF 3.289
Yue Zhou,Qinggang Xu,Xinghua Zhou,Shuang Song,Beiwei Zhu
Bioactive peptides derived from mussels have multiple healthcare functions. Herein, we aimed to examine the effects of mussel peptide preparation on lifespan, stress resistance, apoptosis and aging in Caenorhabditis elegans. Lifespan was determined by counting the number of surviving nematodes daily. ROS level and lipofuscin were measured using a fluorescent microscope. The mussel protein was prepared and hydrolyzed, and then fractionated by ultrafiltration. The fraction (<3 kDa) was purified by gel filtration to obtain the bioactive peptides, and the peptide sequences included in the fractions were identified, which were mostly composed of peptides with <20 amino acid residues. Mussel peptides treatment was found to significantly increase oxidative stress resistance and extend the lifespan of C. elegans. Moreover, this treatment also reduced endogenous ROS level and aging pigments accumulation in C. elegans as well as apoptosis. Collectively, these findings demonstrated that mussel peptides could contribute to healthspan extension of C. elegans through regulating mRNA expression of daf-2 and daf-16. These results highlighted the important role of mussel peptides for food and pharmaceutical industries to develop new nutraceuticals and functional foods.
研究领域:
分子生物学
·
老年学
·
营养保健品
·
功能性食品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2024
·
IF 8.1
Yunjiang Yu,Shihui Tan,Hongzhi Guo,Xin Hua,Haibo Chen,Yue Yang,Dongli Xie,Chuan Yi,Haibo Ling,Mingdeng Xiang
Tetrachlorobisphenol A (TCBPA) has been used as an alternative flame retardant in various fields. However, the long-term effects of TCBPA on the nervous system remain unclear. Thus, Caenorhabditis elegans (L4 larvae) were selected as a model animal to investigate the neurotoxic effects and underlying mechanisms after 10 d of TCBPA exposure. Exposure to TCBPA (0.01–100 μg/L) decreased locomotive behavior in a concentration-dependent manner. In addition, reactive oxygen species (ROS) formation and lipofuscin accumulation were significantly increased, and the expression of sod-3 was upregulated in the exposed nematodes, indicating that TCBPA exposure induced oxidative damage. Furthermore, 100 μg/L TCBPA exposure caused a reduction in dopamine and serotonin levels, and damage in dopaminergic and serotoninergic neurons, which was further confirmed by the downregulated expression of related genes (e.g., dop-1 , dop-3 , cat-1 , and mod-1 ). Molecular docking analysis demonstrated the potential of TCBPA to bind to the neurotransmitter receptor proteins DOP-1, DOP-3, and MOD-1. These results indicate that chronic exposure to TCBPA induces neurotoxic effects on locomotive behavior, which is associated with oxidative stress and damage to dopaminergic and serotoninergic neurons.
研究领域:
毒理学
·
神经科学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Na Li,Xin Fan,Tingjia Chen,Yefan Wang,Zhifeng Tan,Chang Liu,Dayong Zhou,Deyang Li
Color deepening occurs during storage of ready-to-eat (RTE) shrimps, which seriously affects their marketing cycle. This study investigated the molecular mechanisms of color deterioration in RTE shrimps during accelerated storage, shedding light on the pattern of change in colored products and content. The findings revealed significant occurrences of phenolic oxidation, lipid oxidation, and Maillard browning reactions during accelerated storage. Qualitative and quantitative analyses were conducted on the colored products resulting from these chemical reactions. Multivariate mathematical models were employed to analyze the phenolic oxidation products (2-methylanthraquinone and p-benzoquinone), lipid oxidation products (lipofuscin-like pigments and hydrophobic pyrroles), and Maillard browning products (pyrazines and melanoidins). These products were identified as the main contributors to the deepening of the color of RTE shrimps during storage. The outcomes of this research could enhance our understanding of the color change mechanism in thermally processed marine foods, providing valuable insights for quality maintenance and industrial advancement.
研究领域:
食品科学
·
化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Ligang Yu,Jing Wang,Yukun Yang,Caixia Guo,Meiping Li
The objective of this study was to assess the inhibitory impacts of chlorogenic acid (CGA), ferulic acid (FA), and vanillic acid (VA) on advanced lipid oxidation end products (ALEs) generation in bovine serum albumin-linoleic acid models. The addition of 160 μg/mL CGA and VA significantly blocked the formation of lipofuscin-like pigments (LFLP), reducing them by 22.141% ± 1.823% and 12.156% ± 1.296% respectively. It is worth noting that the best inhibition of LFLP by FA was observed at 40 μg/mL (13.105% ± 0.731%). Compared to the control (25.280 ± 1.580 mg/kg protein), thiobarbituric acid reactive substances values were the lowest in the samples containing 160 μg/mL CGA (2.107 ± 0.912 mg/kg protein), 40 μg/mL FA (6.847 ± 1.824 mg/kg protein), and 160 μg/mL VA (10.007 ± 0.912 mg/kg protein) ( P < 0.05). These results suggest that CGA has a more potent inhibitory effect on ALEs formation compared to FA and VA. Therefore, CGA, FA, and VA can be considered as safe dietary phenolic acids for reducing ALEs formation.
研究领域:
食品科学
·
营养学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY
·
2021
·Vol. 124
·期 1
·2100066
·
IF 2.679
Wenjuan Li,Yan Wu,Conghu Li,Liangliang Zhu
Protein modification by active aldehydes is associated with ageing and some chronic diseases, and it is closely related to food quality and safety. In this study, the modification of bovine serum albumin (BSA) using trans,trans-2,4-decadienal at various concentrations (0–10 m m ) is investigated. The results show that the changes in the number of free amino groups and arginine residues, carbonyl formation, aggregation characteristics, and fluorescent lipofuscin-like pigments (LFLP) fluorescence are more severe at (E,E)-2,4-decadienal concentrations of 4–10 m m , whereas the conformational changes are more significant at low concentrations (0.1–2 m m ). In the BSA modified by 1–10 m m (E,E)-2,4-decadienal, the microenvironment of tryptophan residues to become more hydrophobic, the structure became compact, hydrophobic binding sites decreases, molecular weight and particle size increases, and covalently cross-linked heterogeneous aggregates increases. At the same time, the relationship between the oxidation parameters and samples is explained using principal component analysis and hierarchical cluster analysis. Practical Applications : (E,E)-2,4-decadienal is highly electrophilically active with biomacromolecules. However, compared to the widely studied malonaldehyde (MDA), acrolein (ACR), 4-hydroxynonenal (HNE), and 4-oxo-trans-2-nonenal (ONE)-protein adducts, research on the modification of a protein by (E,E)-2,4-decadienal is insufficient, and the chemical nature of (E,E)-2,4-decadienal-protein adducts is not clear. This study may be useful for extending our understanding of the specific role of (E,E)-2,4-decadienal in the formation of modified proteins during the occurrence of chronic diseases and provides a theoretical reference for food quality and safety problems caused by protein carbonylation during processing and storage.
研究领域:
食品科学
·
生物化学
·
蛋白质化学
·
慢性疾病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）