Aging Cell最新文献_第10页

Overexpression of TECPR1 improved cognitive function of P301S-tau mice via activation of autophagy in the early and late process 通过在早期和晚期激活自噬，过表达 TECPR1 可改善 P301S-tau 小鼠的认知功能。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-07 DOI: 10.1111/acel.14404

Ting Li, Ruijuan Liu, Ye He, Bingge Zhang, Xuexiang Rui, Xifei Yang, Jian-Zhi Wang, Juan Zeng, Gang Li, Xiao Li, Gong-Ping Liu

{"title":"Overexpression of TECPR1 improved cognitive function of P301S-tau mice via activation of autophagy in the early and late process","authors":"Ting Li, Ruijuan Liu, Ye He, Bingge Zhang, Xuexiang Rui, Xifei Yang, Jian-Zhi Wang, Juan Zeng, Gang Li, Xiao Li, Gong-Ping Liu","doi":"10.1111/acel.14404","DOIUrl":"10.1111/acel.14404","url":null,"abstract":"Autophagy disorders in AD patients and animal models were well known, however, the effect of P301S-tau on autophagy is not clear. Here, we found that autophagy related protein Tectonin Beta-Propeller Repeat-Containing Protein 1 (TECPR1) decreased in the hippocampus of P301S-tau transgenic mice by proteomics, which was proved in vivo and in vitro, and P301S-tau induced autophagic deficits in early and late process. TECPR1 overexpression attenuated P301S-tau induced autophagy defects via promoting autophagosome generation and autophagosome and lysosomes fusion. We also found that TECPR1 overexpression ameliorated the behavior disorders of P301S-tau mice with promoting tau degradation, improving synaptic plasticity and neuron loss. Lastly, CQ or 3-MA treatment reversed TECPR1 induced improvement effects on autophagic and cognitive disorders, further proved that, TECPR1 activated the early and late process of autophagy to ameliorate the cognition of P301S-tau mice. Our data suggest that TECPR1 is a potential therapy target for AD.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiomic profiling reveals timing of menopause predicts prefrontal cortex aging and cognitive function 多组学特征分析揭示了绝经时间可预测前额叶皮层的衰老和认知功能。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-05 DOI: 10.1111/acel.14395

Fatima Gunter-Rahman, Charleen D. Adams, Ravikiran M. Raju, Yu Zhang, Eunjung Alice Lee, Carmen Messerlian

{"title":"Multiomic profiling reveals timing of menopause predicts prefrontal cortex aging and cognitive function","authors":"Fatima Gunter-Rahman, Charleen D. Adams, Ravikiran M. Raju, Yu Zhang, Eunjung Alice Lee, Carmen Messerlian","doi":"10.1111/acel.14395","DOIUrl":"10.1111/acel.14395","url":null,"abstract":"A new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline. We hypothesized that timing of menopause, a marker of ovarian aging, predicts brain age decades later. We used 2086 subjects with multiple “omics” measurements from post-mortem brain samples. Age at menopause (AAM) is positively correlated with cognitive function and negatively correlated with pre-frontal cortex aging acceleration (calculated as estimated biological age from DNA methylation minus chronological age). Genetic correlations showed that at least part of these associations is derived from shared heritability. To dissect the mechanism linking AAM to cognitive decline, we turned to transcriptomic data which confirmed that later AAM was associated with gene expression in pre-frontal cortex consistent with better cognition, and among those who reached menopause naturally, decreased gene expression of pathways implicated in aging. Those with surgical menopause displayed different molecular changes, including perturbed nicotinamide adenine dinucleotide (NAD+) activity, validated by metabolomics. Bile acid metabolism was perturbed in both groups, although different bile acid ratios were associated with AAM in each. Together, our data suggest that AAM is predictive of brain aging and cognition, with potential mediation by the gut, although through different mechanisms depending on the type of menopause.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated N-glycosylated cathepsin L impairs oocyte function and contributes to oocyte senescence during reproductive aging 在生殖衰老过程中，N-糖基化的凝血酶 L 升高会损害卵母细胞功能并导致卵母细胞衰老。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-04 DOI: 10.1111/acel.14397

Kemei Zhang, Rui Xu, Lu Zheng, Hong Zhang, Zhang Qian, Chuwei Li, Mengqi Xue, Zhaowanyue He, Jinzhao Ma, Zhou Li, Li Chen, Rujun Ma, Bing Yao

{"title":"Elevated N-glycosylated cathepsin L impairs oocyte function and contributes to oocyte senescence during reproductive aging","authors":"Kemei Zhang, Rui Xu, Lu Zheng, Hong Zhang, Zhang Qian, Chuwei Li, Mengqi Xue, Zhaowanyue He, Jinzhao Ma, Zhou Li, Li Chen, Rujun Ma, Bing Yao","doi":"10.1111/acel.14397","DOIUrl":"10.1111/acel.14397","url":null,"abstract":"Age-related declines in oocyte quality and ovarian function are pivotal contributors to female subfertility in clinical settings. Yet, the mechanisms driving ovarian aging and oocyte senescence remain inadequately understood. The present study evaluated the alterations in N-glycoproteins associated with ovarian aging and noted a pronounced elevation in N221 glycopeptides of cathepsin L (Ctsl) in the ovaries of reproductive-aged mice (8–9 months and 11–12 months) compared to younger counterparts (6–8 weeks). Subsequent analysis examined the involvement of Ctsl in oocyte aging and demonstrated a significant elevation in Ctsl levels in aged oocytes. Further, it was revealed that the overexpression of Ctsl in young oocytes substantially diminished their quality, while oocytes expressing an N221-glycosylation mutant of Ctsl did not suffer similar quality degradation. This finding implies that the N221 glycosylation of Ctsl is pivotal in modulating its effect on oocyte health. The introduction of a Ctsl inhibitor into the culture medium restored oocyte quality in aged oocytes by enhancing mitochondrial function, reducing accumulated reactive oxygen species (ROS), lowering apoptosis, and recovering lysosome capacity. Furthermore, the targeted downregulation of Ctsl using siRNA microinjection in aged oocytes enhanced fertilization capability and blastocyst formation, affirming the role of Ctsl knockdown in fostering oocyte quality and embryonic developmental potential. In conclusion, these findings underscore the detrimental effects of high expression of N-glycosylated Ctsl on oocyte quality and its contribution to oocyte senescence, highlighting it as a potential therapeutic target to delay ovarian aging and enhance oocyte viability.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease TMEM16F调节帕金森病细胞模型和小鼠模型中病理性α-突触核蛋白的分泌和扩散。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-02 DOI: 10.1111/acel.14387

Stav Cohen-Adiv, Fatima Amer-Sarsour, Yevgeny Berdichevsky, Emily Boxer, Orly Goldstein, Mali Gana-Weisz, Utkarsh Tripathi, Wote Amelo Rike, Gali Prag, Tanya Gurevich, Nir Giladi, Shani Stern, Avi Orr-Urtreger, Dinorah Friedmann-Morvinski, Avraham Ashkenazi

{"title":"TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease","authors":"Stav Cohen-Adiv, Fatima Amer-Sarsour, Yevgeny Berdichevsky, Emily Boxer, Orly Goldstein, Mali Gana-Weisz, Utkarsh Tripathi, Wote Amelo Rike, Gali Prag, Tanya Gurevich, Nir Giladi, Shani Stern, Avi Orr-Urtreger, Dinorah Friedmann-Morvinski, Avraham Ashkenazi","doi":"10.1111/acel.14387","DOIUrl":"10.1111/acel.14387","url":null,"abstract":"One of the main hallmarks of Parkinson's disease (PD) pathology is the spread of the aggregate-prone protein α-synuclein (α-syn), which can be detected in the plasma and cerebrospinal fluid of patients as well as in the extracellular environment of neuronal cells. The secreted α-syn can exhibit “prion-like” behavior and transmission to naïve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the pathologic process of α-syn is yet to be fully resolved. The TMEM16 family of lipid scramblases and ion channels has been recently associated with cancer and infectious diseases but is less known for its role in aging-related diseases. To elucidate the role of TMEM16F in α-syn spread, we transduced neurons derived from TMEM16F knockout mice with a reporter system that enables the distinction between donor and recipient neurons of pathologic α-synA53T. We found that the spread of α-synA53T was reduced in neurons derived from TMEM16F-knockout mice. These findings were recapitulated in vivo in a mouse model of PD, where attenuated α-synA53T spread was observed when TMEM16F was ablated. Moreover, we identified a single nucleotide polymorphism in TMEM16F of Ashkenazi Jewish PD patients resulting in a missense Ala703Ser mutation with enhanced lipid scramblase activity. This mutation is associated with altered regulation of α-synA53T extracellular secretion in cellular models of PD. Our study highlights TMEM16F as a novel regulator of α-syn spread and as a potential therapeutic target in synucleinopathies.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglia-derived Galectin-9 drives amyloid-β pathology in Alzheimer's disease 小胶质细胞衍生的Galectin-9驱动阿尔茨海默病中的淀粉样蛋白-β病理学。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-11-01 DOI: 10.1111/acel.14396

Guoxin Zhang, Qinyu Peng, Xiaodi Guo, Lina Pan, Min Xiong, Xingyu Zhang, Lijun Dai, Zhaohui Zhang, Tingting Xiao, Juanfeng He, Miao Liu, Wei Ke, Zhentao Zhang

{"title":"Microglia-derived Galectin-9 drives amyloid-β pathology in Alzheimer's disease","authors":"Guoxin Zhang, Qinyu Peng, Xiaodi Guo, Lina Pan, Min Xiong, Xingyu Zhang, Lijun Dai, Zhaohui Zhang, Tingting Xiao, Juanfeng He, Miao Liu, Wei Ke, Zhentao Zhang","doi":"10.1111/acel.14396","DOIUrl":"10.1111/acel.14396","url":null,"abstract":"The accumulation of amyloid-β (Aβ) and overactivation of microglia contribute to the pathogenesis of Alzheimer's disease (AD), but the interaction between microglial activation and Aβ deposition in AD remains elusive. Here we revealed that Aβ activates microglia and promotes the release of Galectin-9 (Gal-9), a member of the β-galactoside–binding family of lectins. The levels of Gal-9 in the cerebrospinal fluid and brain tissues of AD patients are higher than those in control subjects. Gal-9 interacts with Aβ and promotes its aggregation, generating Gal-9-Aβ fibrils with enhanced seeding activity and neurotoxicity. The expression of Gal-9 increases with age in the brains of APP/PS1 transgenic mice. Knockout of Gal-9 in APP/PS1 mice substantially reduced Aβ sedimentation, neuroinflammation, and cognitive impairment. Moreover, depletion of Gal-9 inhibited the seeding activity of brain homogenates from APP/PS1 mice. These findings reveal a mechanism by which microglia-derived Gal-9 accelerates Aβ aggregation and seeding in AD. Thus, strategies aimed at inhibiting Gal-9 may hold promise as a disease-modifying therapy to alleviate AD pathology.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death 内皮细胞特异性早老素表达不会导致心血管改变和过早死亡。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-10-31 DOI: 10.1111/acel.14389

Ignacio Benedicto, Magda R. Hamczyk, Rosa M. Nevado, Ana Barettino, Rosa M. Carmona, Carla Espinós-Estévez, Pilar Gonzalo, Miguel de la Fuente-Pérez, María J. Andrés-Manzano, Cristina González-Gómez, Beatriz Dorado, Vicente Andrés

{"title":"Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death","authors":"Ignacio Benedicto, Magda R. Hamczyk, Rosa M. Nevado, Ana Barettino, Rosa M. Carmona, Carla Espinós-Estévez, Pilar Gonzalo, Miguel de la Fuente-Pérez, María J. Andrés-Manzano, Cristina González-Gómez, Beatriz Dorado, Vicente Andrés","doi":"10.1111/acel.14389","DOIUrl":"10.1111/acel.14389","url":null,"abstract":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis-free mice (LmnaLCS/LCSCdh5-CreERT2) and atheroprone mice (Apoe−/−LmnaLCS/LCSCdh5-CreERT2) with EC-specific progerin expression. Like progerin-free controls, LmnaLCS/LCSCdh5-CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe−/−LmnaLCS/LCSCdh5-CreERT2 mice showed no alteration in body weight or lifespan versus Apoe−/−LmnaLCS/LCS controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Morphological phenotyping of the aging cochlea in inbred C57BL/6N and outbred CD1 mouse strains 近交系 C57BL/6N 和外交系 CD1 小鼠耳蜗老化的形态学表型。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-10-31 DOI: 10.1111/acel.14362

Chiara Attanasio, Antonio Palladino, Daniela Giaquinto, Ferdinando Scavizzi, Marcello Raspa, Chiara Peres, Camilla Anastasio, Paola Scocco, Carla Lucini, Paolo de Girolamo, Livia D'Angelo, Elena De Felice

{"title":"Morphological phenotyping of the aging cochlea in inbred C57BL/6N and outbred CD1 mouse strains","authors":"Chiara Attanasio, Antonio Palladino, Daniela Giaquinto, Ferdinando Scavizzi, Marcello Raspa, Chiara Peres, Camilla Anastasio, Paola Scocco, Carla Lucini, Paolo de Girolamo, Livia D'Angelo, Elena De Felice","doi":"10.1111/acel.14362","DOIUrl":"10.1111/acel.14362","url":null,"abstract":"Morphological mouse phenotyping plays a pivotal role in the translational setting and even more in the area of auditory research, where mouse is a central model organism due to the evolutionary genetic relationship and morpho-functional analogies with the human auditory system. However, some results obtained in murine models cannot be translated to humans due to the inadequate description of experimental conditions underlying poor reproducibility. We approach the characterization of the aging process of the mouse cochlea in animals up to 18 months of age belonging to two of the most used outbred (CD1) and inbred (C57BL/6N) strains. Striving to reduce any environmental variable we performed our study compliantly to the ARRIVE guidelines. We integrated instrumental data (auditory brainstem response test), with morphological analyses to correlate functional discrepancies to morphological changes and track the differences in the evolution of sensorineural hearing loss in the two strains. We featured the localization of Gipc3, Myosin VIIa, and TMC1 in hair cells of the Corti organ as well as NF 200 and the density of type I neuron in the spiral ganglion. We outlined age-related hearing loss (ARHL) in both strains, and a clear drop in the selected marker localization. However, in CD1 we detected a different trend allowing the identification of potential strain-specific mechanisms, namely an increase in myosin VIIa in 6 months aging mice in comparison to 2 months old animals. Our findings represent an asset to investigate the strain-dependent physiological trigger of ARHL providing new insights in the translational area.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arginine metabolism is a biomarker of red blood cell and human aging 精氨酸代谢是红细胞和人体衰老的生物标志物。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-10-30 DOI: 10.1111/acel.14388

Julie A. Reisz, Eric J. Earley, Travis Nemkov, Alicia Key, Daniel Stephenson, Gregory R. Keele, Monika Dzieciatkowska, Steven L. Spitalnik, Eldad A. Hod, Steven Kleinman, Nareg H. Roubinian, Mark T. Gladwin, Kirk C. Hansen, Philip J. Norris, Michael P. Busch, James C. Zimring, Gary A. Churchill, Grier P. Page, Angelo D'Alessandro

{"title":"Arginine metabolism is a biomarker of red blood cell and human aging","authors":"Julie A. Reisz, Eric J. Earley, Travis Nemkov, Alicia Key, Daniel Stephenson, Gregory R. Keele, Monika Dzieciatkowska, Steven L. Spitalnik, Eldad A. Hod, Steven Kleinman, Nareg H. Roubinian, Mark T. Gladwin, Kirk C. Hansen, Philip J. Norris, Michael P. Busch, James C. Zimring, Gary A. Churchill, Grier P. Page, Angelo D'Alessandro","doi":"10.1111/acel.14388","DOIUrl":"10.1111/acel.14388","url":null,"abstract":"Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and were influenced by genetic variation, sex, and body mass index. Integrating multi-omics data and metabolite quantitative trait loci (mQTL) in humans and 525 diversity outbred mice functionally linked metabolism of arginine during RBC storage to increased vesiculation—a hallmark of RBC aging—and lower post-transfusion hemoglobin increments. Thus, arginine metabolism is a biomarker of RBC and organismal aging, suggesting potential new targets for addressing sequelae of aging.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis 半胱氨酸对三种模式生物寿命的影响：系统综述和荟萃分析。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-10-30 DOI: 10.1111/acel.14392

Yue Ma, Mengqi Chen, Kaiyao Huang, Wakam Chang

{"title":"The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis","authors":"Yue Ma, Mengqi Chen, Kaiyao Huang, Wakam Chang","doi":"10.1111/acel.14392","DOIUrl":"10.1111/acel.14392","url":null,"abstract":"Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N-acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti-aging effects of cysteine, we systematically reviewed and performed a meta-analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heat exposure promotes sarcopenia via gut microbiota-derived metabolites 热暴露通过肠道微生物群衍生的代谢物促进肌少症。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-10-29 DOI: 10.1111/acel.14370

Yi-Fan Guo, Zhe-Yu Liu, Min Zhou, Wei-Hong Kuang, Ya Liu, Yan Huang, Ping Yin, Zhu-Ying Xia

{"title":"Heat exposure promotes sarcopenia via gut microbiota-derived metabolites","authors":"Yi-Fan Guo, Zhe-Yu Liu, Min Zhou, Wei-Hong Kuang, Ya Liu, Yan Huang, Ping Yin, Zhu-Ying Xia","doi":"10.1111/acel.14370","DOIUrl":"10.1111/acel.14370","url":null,"abstract":"The unprecedented rise in global ambient temperatures in the last decade has significantly impacted human health, yet how heat exposure affects the development of sarcopenia remains enigmatic. Here, we demonstrate that chronic heat exposure induces skeletal muscle volume loss, leading to muscle strength and functional decline in mice. The microbiota composition of heat-exposed mice was analyzed using 16S ribosomal DNA analysis. Liquid chromatography-mass spectrometry (LC–MS) was used to explore the effects of heat exposure on the blood metabolome and to further analyze the correlation between blood metabolism and gut microbiota. Transplantation of microbiota from heat-exposed mice to germ-free mice was sufficient to increase adverse effects on skeletal muscle function in the host. Mechanistically, using an untargeted metabolomics strategy, we reveal that altered gut microbiota due to high temperatures is associated with elevated serum levels of homocitrulline. Homocitrulline causes mitochondrial dysfunction in myocytes by exacerbating ferroptosis levels. And Nrf2 activator (Oltipraz) supplementation alleviates muscle atrophy and dysfunction induced by heat exposure. Our findings reveal the detrimental effects of heat exposure on muscle function and provide new strategies for treating sarcopenia.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0