Aging Cell最新文献_第9页

Temperature-dependent lifespan extension is achieved in miR-80-deleted Caenorhabditis elegans by NLP-45 to modulate endoplasmic reticulum unfolded protein responses. 通过NLP-45调节内质网折叠蛋白反应，在miR-80缺失的秀丽隐杆线虫中实现了温度依赖性寿命延长。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-25 DOI: 10.1111/acel.14345

Chunlin Zhao, Jintao Luo, Yuqiang Zhang, Yong Yu

{"title":"Temperature-dependent lifespan extension is achieved in miR-80-deleted Caenorhabditis elegans by NLP-45 to modulate endoplasmic reticulum unfolded protein responses.","authors":"Chunlin Zhao, Jintao Luo, Yuqiang Zhang, Yong Yu","doi":"10.1111/acel.14345","DOIUrl":"https://doi.org/10.1111/acel.14345","url":null,"abstract":"MicroRNA plays a crucial role in post-transcriptional gene regulation and has recently emerged as a factor linked to aging, but the underlying regulatory mechanisms remain incompletely understood. In this study, we observed lifespan-extending effects in miR-80-deficient Caenorhabditis elegans at 20°C but not 25°C. At 20°C, miR-80 deletion leads to NLP-45 upregulation, which positively correlates to increased abu transcripts and extended lifespan. Supportively, we identified miR-80 binding regions in the 5' and 3' UTR of nlp-45. As the temperature rises to 25°C, wildtype increases miR-80 levels, but removal of miR-80 is accompanied by decreased nlp-45 expression, suggesting intervention from other temperature-sensitive mechanisms. These findings support the concept that microRNAs and neuropeptide-like proteins can form molecular regulatory networks involving downstream molecules to regulate lifespan, and such regulatory effects vary on environmental conditions. This study unveils the role of an axis of miR-80/NLP-45/UPRER components in regulating longevity, offering new insights on strategies of aging attenuation and health span prolongation.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14345"},"PeriodicalIF":8.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging disrupts locus coeruleus-driven norepinephrine transmission in the prefrontal cortex: Implications for cognitive and motor decline. 衰老会破坏前额叶皮层中由脑室小叶驱动的去甲肾上腺素传递：对认知能力和运动能力衰退的影响。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-23 DOI: 10.1111/acel.14342

Evgeny Budygin, Valentina Grinevich, Zhong-Min Wang, María Laura Messi, William Ryan Meeker, Jie Zhang, William Matthew Stewart, Carol Milligan, Osvaldo Delbono

{"title":"Aging disrupts locus coeruleus-driven norepinephrine transmission in the prefrontal cortex: Implications for cognitive and motor decline.","authors":"Evgeny Budygin, Valentina Grinevich, Zhong-Min Wang, María Laura Messi, William Ryan Meeker, Jie Zhang, William Matthew Stewart, Carol Milligan, Osvaldo Delbono","doi":"10.1111/acel.14342","DOIUrl":"10.1111/acel.14342","url":null,"abstract":"The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating the neurobiological basis of age-related cognitive and motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, and notable changes in locomotor behavior. The neurochemical foundations of these deficits were investigated through fast-scan cyclic voltammetry to measure NE release in the PFC and LC, both in vivo and in brain slices. Additionally, oxygen levels were monitored as a proxy for PFC neuronal function, and NE levels were analyzed in the extracellular space via microdialysis and total content in the PFC. Aged mice exhibited a frequency-dependent increase in NE release in the PFC upon LC stimulation, suggesting alterations in neural responsiveness due to aging. We also recorded slower NE reuptake rates and increased NE content and neuronal activity, indicated by higher oxygen levels and facilitated neuron activation due to membrane depolarization recorded via whole-cell patch-clamp. To understand the basis for LC-driven NE surges in the PFC with aging, we examined the expression levels of two proteins critical for presynaptic NE release and NE reuptake: the α2a-adrenergic receptor and the NE transporter. Both showed a significant decrease in the PFC with aging. These findings support the concept that aging significantly alters the structural and functional dynamics within the LC-PFC neural circuit, impacting NE modulation and neuronal activity, which may underlie the observed declines in cognitive and motor functions in aging populations.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14342"},"PeriodicalIF":8.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

2'-Fucosyllactose attenuates aging-related metabolic disorders through modulating gut microbiome-T cell axis. 2'-Fucosyllactose 通过调节肠道微生物-T 细胞轴减轻与衰老相关的代谢紊乱。

IF 8 1区医学

Aging Cell Pub Date : 2024-09-20 DOI: 10.1111/acel.14343

Ang Li, Ruixin Kou, Ruishan Wang, Jin Wang, Bowei Zhang, Jingmin Liu, Yaozhong Hu, Shuo Wang

{"title":"2'-Fucosyllactose attenuates aging-related metabolic disorders through modulating gut microbiome-T cell axis.","authors":"Ang Li, Ruixin Kou, Ruishan Wang, Jin Wang, Bowei Zhang, Jingmin Liu, Yaozhong Hu, Shuo Wang","doi":"10.1111/acel.14343","DOIUrl":"https://doi.org/10.1111/acel.14343","url":null,"abstract":"Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including Ligilactobacillus, Colidextribacter, Mucispirillum, and Lachnoclostridium, and increased abundance of harmful bacteria including Turicibacter and Desulfovibrio, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14343"},"PeriodicalIF":8.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oocytes maintain low ROS levels to support the dormancy of primordial follicles 卵母细胞维持较低的 ROS 水平，以支持原始卵泡休眠

IF 7.8 1区医学

Aging Cell Pub Date : 2024-09-19 DOI: 10.1111/acel.14338

Shaogang Qin, Xinyue Chi, Zijian Zhu, Chuanhe Chen, Tuo Zhang, Meina He, Meng Gao, Ting Zhao, Jingwen Zhang, Lifan Zhang, Wenying Zheng, Ziqi Chen, Wenji Wang, Bo Zhou, Guoliang Xia, Chao Wang

{"title":"Oocytes maintain low ROS levels to support the dormancy of primordial follicles","authors":"Shaogang Qin, Xinyue Chi, Zijian Zhu, Chuanhe Chen, Tuo Zhang, Meina He, Meng Gao, Ting Zhao, Jingwen Zhang, Lifan Zhang, Wenying Zheng, Ziqi Chen, Wenji Wang, Bo Zhou, Guoliang Xia, Chao Wang","doi":"10.1111/acel.14338","DOIUrl":"https://doi.org/10.1111/acel.14338","url":null,"abstract":"Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"2 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles 左右心室衰老的分子和生理机制各不相同

IF 7.8 1区医学

Aging Cell Pub Date : 2024-09-19 DOI: 10.1111/acel.14339

Benjamin D. McNair, Aykhan Yusifov, Joshua P. Thornburg, Caleb R. Hoopes, Sushumna B. Satyanarayana, Tathagato Roy, Jason P. Gigley, Danielle R. Bruns

{"title":"Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles","authors":"Benjamin D. McNair, Aykhan Yusifov, Joshua P. Thornburg, Caleb R. Hoopes, Sushumna B. Satyanarayana, Tathagato Roy, Jason P. Gigley, Danielle R. Bruns","doi":"10.1111/acel.14339","DOIUrl":"https://doi.org/10.1111/acel.14339","url":null,"abstract":"Aging is the primary risk factor for heart disease, the leading global cause of death. Right ventricular (RV) function predicts survival in several age-related clinical contexts, yet no therapies directly improve RV function, in large part due to a poor mechanistic understanding of RV aging and how it is distinct from the widely studied left ventricle (LV). To address this gap, we comprehensively quantified RV functional and morphological remodeling with age. We further aimed to identify molecular mechanisms of RV aging thus we performed RNAseq on RV and LV from male and female young (4 months) and aged (19–21 months) C57BL6 mice. Contrary to the concentric hypertrophic remodeling and diastolic dysfunction that occurs in the LV, the aging RV underwent eccentric remodeling with significant dilation and impaired systolic function. Transcriptomic data were also consistent with ventricle-specific aging, with few genes (13%) similarly shared between ventricles with aging. KEGG analysis identified shared aging genes in inflammatory and immune cell pathways that were confirmed by flow cytometry that demonstrated higher percent of GR1+ myeloid cells in both ventricles. Unique RV aging genes enriched in the biosynthesis of saturated fatty acids, PPAR signaling, and butanoate metabolism, and we identified putative novel RV-specific aging genes. Together, we suggest that the RV and LV are unique cardiac chambers that undergo distinct remodeling with age. These robust differences may explain why therapies designed from LV-based studies fail to improve RV function and suggest that future efforts emphasizing ventricular differences may elucidate new therapies for healthy cardiac aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"1 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of AS1842856 as a novel small‐molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis 通过加速 GSK3α/β 外渗，鉴定 AS1842856 为一种新型小分子 GSK3α/β 抑制剂，可防治 Tauopathy

IF 7.8 1区医学

Aging Cell Pub Date : 2024-09-17 DOI: 10.1111/acel.14336

Da‐Long He, Xiao‐Yu Zhang, Jing‐Yang Su, Qi Zhang, Ling‐Xiao Zhao, Ting‐Yao Wu, Hang Ren, Rong‐Jun Jia, Xian‐Fang Lei, Wen‐Jia Hou, Wen‐Ge Sun, Yong‐Gang Fan, Zhan‐You Wang

{"title":"Identification of AS1842856 as a novel small‐molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis","authors":"Da‐Long He, Xiao‐Yu Zhang, Jing‐Yang Su, Qi Zhang, Ling‐Xiao Zhao, Ting‐Yao Wu, Hang Ren, Rong‐Jun Jia, Xian‐Fang Lei, Wen‐Jia Hou, Wen‐Ge Sun, Yong‐Gang Fan, Zhan‐You Wang","doi":"10.1111/acel.14336","DOIUrl":"https://doi.org/10.1111/acel.14336","url":null,"abstract":"Glycogen synthase kinase‐3α/β (GSK3α/β) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/β inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/β. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/β content in a FOXO1‐independent manner. Specifically, AS directly bound to GSK3α/β, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/β content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood–brain barrier (BBB) using an imaging mass microscope. Long‐term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/β expression in the brain. Altogether, AS represents a novel small‐molecule GSK3α/β inhibitor that facilitates GSK3α/β exocytosis, holding promise as a therapeutic agent for GSK3α/β hyperactivation‐associated disorders.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"49 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Featured Cover 特色封面

IF 7.8 1区医学

Aging Cell Pub Date : 2023-10-16 DOI: 10.1111/acel.14016

Hasan Ishtayeh, Margarita Galves, Tania T. Barnatan, Yevgeny Berdichevsky, Fatima Amer-Sarsour, Metsada Pasmanik-Chor, Itzhak Braverman, Sergiu C. Blumen, Avraham Ashkenazi

引用次数: 0

Intersection clock reveals a rejuvenation event during human embryogenesis 交叉点时钟揭示了人类胚胎发生过程中的再生事件。

IF 7.8 1区医学

Aging Cell Pub Date : 2023-10-02 DOI: 10.1111/acel.13922

Csaba Kerepesi, Vadim N. Gladyshev

{"title":"Intersection clock reveals a rejuvenation event during human embryogenesis","authors":"Csaba Kerepesi, Vadim N. Gladyshev","doi":"10.1111/acel.13922","DOIUrl":"10.1111/acel.13922","url":null,"abstract":"Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naïve (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naïve cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093534","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: 1

Transcriptional changes of the aging lung 衰老肺的转录变化。

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-14 DOI: 10.1111/acel.13969

Minxue Jia, Paula A. Agudelo Garcia, Jose A. Ovando-Ricardez, Tracy Tabib, Humberto T. Bittar, Robert A. Lafyatis, Ana L. Mora, Panayiotis V. Benos, Mauricio Rojas

{"title":"Transcriptional changes of the aging lung","authors":"Minxue Jia, Paula A. Agudelo Garcia, Jose A. Ovando-Ricardez, Tracy Tabib, Humberto T. Bittar, Robert A. Lafyatis, Ana L. Mora, Panayiotis V. Benos, Mauricio Rojas","doi":"10.1111/acel.13969","DOIUrl":"10.1111/acel.13969","url":null,"abstract":"Aging is a natural process associated with declined organ function and higher susceptibility to developing chronic diseases. A systemic single-cell type-based study provides a unique opportunity to understand the mechanisms behind age-related pathologies. Here, we use single-cell gene expression analysis comparing healthy young and aged human lungs from nonsmoker donors to investigate age-related transcriptional changes. Our data suggest that aging has a heterogenous effect on lung cells, as some populations are more transcriptionally dynamic while others remain stable in aged individuals. We found that monocytes and alveolar macrophages were the most transcriptionally affected populations. These changes were related to inflammation and regulation of the immune response. Additionally, we calculated the LungAge score, which reveals the diversity of lung cell types during aging. Changes in DNA damage repair, fatty acid metabolism, and inflammation are essential for age prediction. Finally, we quantified the senescence score in aged lungs and found that the more biased cells toward senescence are immune and progenitor cells. Our study provides a comprehensive and systemic analysis of the molecular signatures of lung aging. Our LungAge signature can be used to predict molecular signatures of physiological aging and to detect common signatures of age-related lung diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598259","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: 1

Erratum to: The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α 勘误表：中心体扩增诱导的变异衰老相关分泌表型构成了激活缺氧诱导因子-1α的途径

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-11 DOI: 10.1111/acel.13991

引用次数: 0