Aging Cell最新文献_第9页

The Effect of Advancing Age and Intraocular Pressure Injury on Retinal Ganglion Cell Function and Synaptic Connectivity. 年龄增长和眼压损伤对视网膜神经节细胞功能和突触连接的影响

IF 8 1区医学

Aging Cell Pub Date : 2025-02-27 DOI: 10.1111/acel.70005

Vicki Chrysostomou, Sevannah Ellis, Lewis E Fry, Robert J Hatch, Eamonn T Fahy, Katharina C Bell, Ian A Trounce, Peter van Wijngaarden, Steve Petrou, Jonathan G Crowston

{"title":"The Effect of Advancing Age and Intraocular Pressure Injury on Retinal Ganglion Cell Function and Synaptic Connectivity.","authors":"Vicki Chrysostomou, Sevannah Ellis, Lewis E Fry, Robert J Hatch, Eamonn T Fahy, Katharina C Bell, Ian A Trounce, Peter van Wijngaarden, Steve Petrou, Jonathan G Crowston","doi":"10.1111/acel.70005","DOIUrl":"https://doi.org/10.1111/acel.70005","url":null,"abstract":"Age and elevated intraocular pressure (IOP) are the two major risk factors for developing glaucoma, a leading cause of blindness worldwide that is characterized by the loss of retinal ganglion cells (RGCs). Although vision loss is irreversible over the long term, accumulating evidence points to short-term improvement of vision in glaucoma patients in response to certain interventions, suggesting that RGCs have the capacity to recover function. In the present study, we sought to investigate the mechanisms underlying loss and recovery of RGC function in response to aging and IOP injury, with a focus on synaptic connectivity. Using electroretinography, we found that advancing age was associated with a substantial reduction in function across all retinal layers in the absence of significant cell loss. A superimposed injury induced by IOP elevation led to the selective loss of RGC function in young and middle-aged mice that was associated with a decrease in paired excitatory synapses. RGC functional recovery after injury was significantly delayed in middle-aged mice and was mediated through different cellular mechanisms than in young mice. Whereas young mice regained excitatory synaptic inputs from bipolar cells, functional recovery in older mice was instead mediated through an increase in intrinsic RGC excitability, associated with modulation of the action potential threshold and axon initial segment length. Our findings provide new insights into the impact of advancing age on RGC resilience to IOP injury. Boosting the capacity for RGC recovery by reversing the effect of advancing age offers a new therapeutic approach for glaucoma management.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70005"},"PeriodicalIF":8.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522171","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

Circular RNA Telomerase Reverses Endothelial Senescence in Progeria. 环状 RNA 端粒酶可逆转早衰症的内皮衰老

IF 8 1区医学

Aging Cell Pub Date : 2025-02-23 DOI: 10.1111/acel.70021

Weifeng Qin, Kathrina D Castillo, Hongye Li, Thi Kim Cuc Nguyen, Daniel L Kiss, John P Cooke, Anahita Mojiri

{"title":"Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.","authors":"Weifeng Qin, Kathrina D Castillo, Hongye Li, Thi Kim Cuc Nguyen, Daniel L Kiss, John P Cooke, Anahita Mojiri","doi":"10.1111/acel.70021","DOIUrl":"https://doi.org/10.1111/acel.70021","url":null,"abstract":"Telomeres shorten with each cell division, acting as a chronometer of cell age. The enzyme telomerase, primarily active in stem cells, reverses telomere erosion. We have previously observed that transient transfection with human TERT mRNA extends telomeres and mitigates hallmarks of senescence in replicatively aged human cells or those affected by Hutchinson-Gilford progeroid syndrome (HGPS). However, due to its short half-life, mRNA requires frequent administration. In this study, we hypothesized that TERT circular (circ) RNA would extend the duration of telomerase expression and be more effective at reversing hallmarks of senescence in endothelial cells derived from HGPS patients. We observe that a single transfection of TERT circRNA is more effective than mRNA in the extension of telomere length, as determined by quantitative fluorescence in situ hybridization. Furthermore, TERT circRNA reduced the number of β-gal positive cells by three-fold and normalized nuclear morphology in HGPS endothelial cells (HGPS-ECs). Moreover, TERT circRNA substantially reduced senescent markers, inflammatory markers, and DNA damage markers, including Progerin, p16, p21, IL-1B, IL-6, IL-8, MCP1, and γH2AX. Additionally, it restored NO production, enhanced cell proliferation, promoted angiogenesis, improved LDL uptake, reduced mitochondrial ROS, and normalized mitochondrial membrane potential more effectively. Our data suggest that TERT circRNA is superior to linear TERT mRNA in reversing processes involved in senescence.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70021"},"PeriodicalIF":8.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481794","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

Age-Dependent Clonal Expansion of Non-Sperm-Forming Spermatogonial Stem Cells in Mouse Testes. 非精子形成精原干细胞在小鼠睾丸中的年龄依赖性克隆扩增。

IF 8 1区医学

Aging Cell Pub Date : 2025-02-22 DOI: 10.1111/acel.70019

Terumichi Kawahara, Shinnosuke Suzuki, Toshinori Nakagawa, Yuki Kamo, Miki Kanouchi, Miyako Fujita, Maki Hattori, Atsuko Suzuki, Kentaro Tanemura, Shosei Yoshida, Kenshiro Hara

{"title":"Age-Dependent Clonal Expansion of Non-Sperm-Forming Spermatogonial Stem Cells in Mouse Testes.","authors":"Terumichi Kawahara, Shinnosuke Suzuki, Toshinori Nakagawa, Yuki Kamo, Miki Kanouchi, Miyako Fujita, Maki Hattori, Atsuko Suzuki, Kentaro Tanemura, Shosei Yoshida, Kenshiro Hara","doi":"10.1111/acel.70019","DOIUrl":"https://doi.org/10.1111/acel.70019","url":null,"abstract":"In male mammals, spermatogonial stem cells (SSCs) are essential for sustaining lifelong spermatogenesis within the testicular open niche, a unique environment that allows SSC migration over an extended niche area. As SSCs undergo continuous mitotic division, mutations accumulate and are transmitted to the descendant SSC clones. Therefore, SSC clonal fate behaviors, in terms of their efficiencies in completing spermatogenesis and undergoing expansion within the niche, influence sperm genomic diversity. We aimed to elucidate the effects of physiological aging on SSC clonal fate behavior within the testicular open niche. We used single-cell RNA sequencing, lineage tracing, and intravital live imaging to investigate SSC behavior in aged mouse testes, where spermatogenesis, although reduced, persists. We found that undifferentiated spermatogonia maintained gene expression heterogeneity during aging. Among these, GFRα1+ cells, which exhibited state heterogeneity, showed accelerated proliferation and persistent motility, continuing to function as SSCs in older mice. In contrast, a subset of SSCs characterized by low Egr4 and Cops5 expression did not contribute to spermatid formation. These non-sperm-forming SSC clones increased in proportion among the total SSC clones and expanded spatially within the testicular open niche in old mice, a phenomenon not observed in young mice. The expansion of non-sperm-forming SSC clones in aged testes suggests that they occupy a niche space, limiting the availability of functional SSCs and potentially reducing sperm production and genetic diversity. These findings highlight age-specific clonal characteristics as hallmarks of stem cell aging within the testicular open niche and provide novel insights into the mechanisms governing reproductive aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70019"},"PeriodicalIF":8.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476160","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

The Impact of Toll-Like Receptor 5 on Liver Function in Age-Related Metabolic Disorders. toll样受体5对年龄相关代谢紊乱患者肝功能的影响

IF 8 1区医学

Aging Cell Pub Date : 2025-02-17 DOI: 10.1111/acel.70009

Dong-Hyun Kim, Hye Sun Go, Eun Jae Jeon, Thi Quynh Trang Nguyen, Da Yeon Kim, Hansung Park, Hyo-Ji Eom, Sung Young Kim, Sang Chul Park, Kyung A Cho

{"title":"The Impact of Toll-Like Receptor 5 on Liver Function in Age-Related Metabolic Disorders.","authors":"Dong-Hyun Kim, Hye Sun Go, Eun Jae Jeon, Thi Quynh Trang Nguyen, Da Yeon Kim, Hansung Park, Hyo-Ji Eom, Sung Young Kim, Sang Chul Park, Kyung A Cho","doi":"10.1111/acel.70009","DOIUrl":"https://doi.org/10.1111/acel.70009","url":null,"abstract":"Toll-like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends the healthspan and lifespan of aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5 deficiency induces gene expression changes in liver tissue similar to those caused by the methionine-choline deficient (MCD) diet, particularly affecting lipid metabolism and circadian rhythm-related genes. TLR5 knockout (TLR5 KO) mice displayed an increased propensity for liver fibrosis and lipid accumulation under the MCD diet, exacerbating liver pathology. Both hepatocytes and hepatic stellate cells in TLR5 KO mice were functionally impacted, leading to metabolic dysfunction and fibrosis. These findings suggest that TLR5 could be a significant target for addressing metabolic diseases that arise and worsen with aging. Furthermore, understanding the mechanisms by which TLR5 activation extends healthspan could provide valuable insights into therapeutic strategies for enhancing longevity and managing age-related metabolic disorders.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70009"},"PeriodicalIF":8.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432089","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

Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice. RPE中激活的mTOR信号驱动EMT、自噬和代谢破坏，导致小鼠amd样病理。

IF 8 1区医学

Aging Cell Pub Date : 2025-02-17 DOI: 10.1111/acel.70018

Olivia Chowdhury, Sridhar Bammidi, Pooja Gautam, Vishnu Suresh Babu, Haitao Liu, Peng Shang, Ying Xin, Emma Mahally, Mihir Nemani, Victoria Koontz, Kira Lathrop, Katarzyna M Kedziora, Jonathan Franks, Ming Sun, Joshua W Smith, Lauren R DeVine, Robert N Cole, Nadezda Stepicheva, Anastasia Strizhakova, Sreya Chattopadhyay, Stacey Hose, Jacob Samuel Zigler, José-Alain Sahel, Jiang Qian, Prasun Guha, James T Handa, Sayan Ghosh, Debasish Sinha

{"title":"Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.","authors":"Olivia Chowdhury, Sridhar Bammidi, Pooja Gautam, Vishnu Suresh Babu, Haitao Liu, Peng Shang, Ying Xin, Emma Mahally, Mihir Nemani, Victoria Koontz, Kira Lathrop, Katarzyna M Kedziora, Jonathan Franks, Ming Sun, Joshua W Smith, Lauren R DeVine, Robert N Cole, Nadezda Stepicheva, Anastasia Strizhakova, Sreya Chattopadhyay, Stacey Hose, Jacob Samuel Zigler, José-Alain Sahel, Jiang Qian, Prasun Guha, James T Handa, Sayan Ghosh, Debasish Sinha","doi":"10.1111/acel.70018","DOIUrl":"https://doi.org/10.1111/acel.70018","url":null,"abstract":"The mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are crucial for various physiological functions. Although the role of mTORC1 in retinal pigmented epithelium (RPE) homeostasis and age-related macular degeneration (AMD) pathogenesis is established, the function of mTORC2 remains unclear. We investigated both complexes in RPE health and disease. Therefore, in this study, we have attempted to demonstrate that the specific overexpression of mammalian lethal with Sec13 protein 8 (mLST8) in the mouse RPE activates both mTORC1 and mTORC2, inducing epithelial-mesenchymal transition (EMT)-like changes and subretinal/RPE deposits resembling early AMD-like pathogenesis. Aging in these mice leads to RPE degeneration, causing retinal damage, impaired debris clearance, and metabolic and mitochondrial dysfunction. Inhibition of mTOR with TORIN1 in vitro or βA3/A1-crystallin in vivo normalized mTORC1/2 activity and restored function, revealing a novel role for the mTOR complexes in regulating RPE function, impacting retinal health and disease.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70018"},"PeriodicalIF":8.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432087","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

Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments. 健康衰老的代谢组学和蛋白质组学特征跨越多个生理区室。

IF 8 1区医学

Aging Cell Pub Date : 2025-02-14 DOI: 10.1111/acel.70014

R Moaddel, J Candia, C Ubaida-Mohien, T Tanaka, A Z Moore, M Zhu, G Fantoni, S Church, J D'Agostino, J Fan, N Shehadeh, S De, E Lehrmann, M Kaileh, E Simonsick, R Sen, J M Egan, L Ferrucci

{"title":"Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments.","authors":"R Moaddel, J Candia, C Ubaida-Mohien, T Tanaka, A Z Moore, M Zhu, G Fantoni, S Church, J D'Agostino, J Fan, N Shehadeh, S De, E Lehrmann, M Kaileh, E Simonsick, R Sen, J M Egan, L Ferrucci","doi":"10.1111/acel.70014","DOIUrl":"https://doi.org/10.1111/acel.70014","url":null,"abstract":"The study of biomarkers in biofluids and tissues expanded our understanding of the biological processes that drive physiological and functional manifestations of aging. However, most of these studies were limited to examining one biological compartment, an approach that fails to recognize that aging pervasively affects the whole body. The simultaneous modeling of hundreds of metabolites and proteins across multiple compartments may provide a more detailed picture of healthy aging and point to differences between chronological and biological aging. Herein, we report proteomic analyses of plasma and urine collected in healthy men and women, age 22-92 years. Using these data, we developed a series of metabolomic and proteomic predictors of chronological age for plasma, urine, and skeletal muscle. We then defined a biological aging score, which measures the departure between an individual's predicted age and the expected predicted age for that individual based on the full cohort. We show that these predictors are significantly and independently related to clinical phenotypes important for aging, such as inflammation, iron deficiency anemia, muscle mass, and renal and hepatic functions. Despite a different set of selected biomarkers in each compartment, the different scores reflect a similar degree of deviation from healthy aging in single individuals, thus allowing identification of subjects with significant accelerated or decelerated biological aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70014"},"PeriodicalIF":8.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424478","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

Negative Effect of Gst-35 on the Health Span of Caenorhabditis elegans Through Lysosomal Dysfunction via the Pmk-1 and Skr Genes. Gst-35通过Pmk-1和Skr基因的溶酶体功能障碍对秀丽隐杆线虫健康寿命的负面影响

IF 8 1区医学

Aging Cell Pub Date : 2025-02-13 DOI: 10.1111/acel.70016

Yehui Gao, Xinyun Zhang, Congmin Wei, Hongru Lin, Mengchen Wu, Botian Ma, Jinyun Jiang, Shan Li, Hongbing Wang

{"title":"Negative Effect of Gst-35 on the Health Span of Caenorhabditis elegans Through Lysosomal Dysfunction via the Pmk-1 and Skr Genes.","authors":"Yehui Gao, Xinyun Zhang, Congmin Wei, Hongru Lin, Mengchen Wu, Botian Ma, Jinyun Jiang, Shan Li, Hongbing Wang","doi":"10.1111/acel.70016","DOIUrl":"https://doi.org/10.1111/acel.70016","url":null,"abstract":"As global life expectancy increases, the focus has shifted from merely extending lifespan to promoting healthy aging. GSTA1, GSTA2, and GSTA3 (GSTA1-3), members of the alpha class of glutathione S-transferases, are involved in diverse biological processes, including metabolism and immune regulation, highlighting their potential influence on human health span and lifespan. In this study, we employed Caenorhabditis elegans as a model organism to investigate the role of gst-35, an ortholog of mammalian GSTA1-3, in healthy aging. Our results demonstrated that gst-35 overexpression has detrimental effects on multiple physiological functions in nematodes. Specifically, gst-35 overexpression significantly reduced lifespan, impaired development and growth, and substantially diminished reproductive capacity, physical fitness, and stress resistance. In contrast, gst-35 knockout partially enhanced physical fitness and stress resistance. Comprehensive RNA-sequencing transcriptome analysis revealed that gst-35 overexpression disrupted metabolic homeostasis and induced lysosomal dysfunction. These effects were mediated through the activation of the pmk-1 signaling pathway and suppression of skr genes, which collectively impaired healthy aging processes. These findings illuminate the complex role of gst-35 in aging and provide valuable insights into the molecular mechanisms underlying healthy aging, offering potential targets for interventions aimed at promoting health span.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70016"},"PeriodicalIF":8.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404974","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

Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species. DNA拓扑异构酶Top2的减少重编程表观遗传景观并延长物种的健康和寿命。

IF 8 1区医学

Aging Cell Pub Date : 2025-02-12 DOI: 10.1111/acel.70010

Man Zhu, Meng Ma, Lunan Luo, Feiyang Li, Jiashun Zheng, Yan Pan, Lu Yang, Ying Xiao, Ziyan Wang, Bo Xian, Yi Zheng, Hao Li, Jing Yang

引用次数: 0

Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening. 用于加速衰老研究和抗衰老药物筛选的短端粒斑马鱼模型的建立

IF 8 1区医学

Aging Cell Pub Date : 2025-02-08 DOI: 10.1111/acel.70007

David Hernández-Silva, María D López-Abellán, Francisco J Martínez-Navarro, Jesús García-Castillo, María L Cayuela, Francisca Alcaraz-Pérez

{"title":"Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening.","authors":"David Hernández-Silva, María D López-Abellán, Francisco J Martínez-Navarro, Jesús García-Castillo, María L Cayuela, Francisca Alcaraz-Pérez","doi":"10.1111/acel.70007","DOIUrl":"https://doi.org/10.1111/acel.70007","url":null,"abstract":"Increased life expectancy is associated with a higher risk of age-related diseases, which represent a major public health challenge. Animal models play a crucial role in aging research, enabling the study of diseases at the organism level and facilitating drug development and repurposing. Among these models, zebrafish stands out as an excellent in vivo system due to its unique characteristics. However, the longevity of zebrafish is a limitation for research, as it often takes too long to obtain results within a reasonable timeframe. To address this, we have developed a short telomere zebrafish line (ST2) with a premature aging phenotype during the larval stage. Although less extreme than the tert-deficient G2 larvae, ST2 larvae exhibit reduced telomerase expression and activity, along with shortened telomeres. they also exhibit increased cellular senescence, apoptosis, and premature death. As a proof of concept, we evaluated the antiaging effects of two compounds: resveratrol (a polyphenol) and navitoclax (a senolytic). Our results confirm the antiaging properties of resveratrol, which improves telomere maintenance. However, navitoclax does not attenuate the ST2 phenotype. Taking advantage of the zebrafish larval model, this premature aging system provides a valuable platform for in vivo testing of rejuvenating molecules through drug screening, using telomere length or survival as a readout.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70007"},"PeriodicalIF":8.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373657","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

Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females. 生殖引发的固醇竞争加剧了雌性果蝇与年龄相关的肠道屏障损伤。

IF 8 1区医学

Aging Cell Pub Date : 2025-02-07 DOI: 10.1111/acel.70011

Guixiang Yu, Kejin Chen, Mingyao Yang, Qi Wu

{"title":"Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females.","authors":"Guixiang Yu, Kejin Chen, Mingyao Yang, Qi Wu","doi":"10.1111/acel.70011","DOIUrl":"https://doi.org/10.1111/acel.70011","url":null,"abstract":"The trade-off between reproduction and lifespan has been documented across a wide array of organisms, ranging from invertebrates to mammals. In malnourishing dietary conditions, inhibition of the reproductive processes generally extends the lifespan of females. However, the underlying mechanisms through which nutritional competition driven by reproduction accelerates aging remain poorly understood. Here, using female Drosophila melanogaster as a model, we show that among various dietary conditions lacking specific nutrients, only sterol deficiency significantly exacerbated both the incidence and severity of intestinal barrier deterioration during aging. Sterile mutation specifically ameliorated such damage in sterol-deprived diets, but failed to alleviate age-related intestinal barrier deterioration under other nutritional conditions. Additionally, we demonstrate that the lifespan extension and intestinal barrier amelioration, accompanied by a reproductive suppression effect, through the pharmacological inhibition of mTOR or Ras-Erk signaling using rapamycin or trametinib, were significantly modulated by cholesterol levels. Our study also identifies the morphological changes in excreta as a sensitive biomarker for early intestinal dysfunction. Collectively, these results suggest that the impairment of the intestinal barrier caused by reproductive-induced sterol competition constitutes a significant factor limiting female lifespan in nutritionally unbalanced diets. This work elucidates a salient aspect of the complex interplay between reproductive resource allocation and somatic maintenance, thereby enhancing our understanding of how diet impacts the aging process.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70011"},"PeriodicalIF":8.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373658","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