Aging Cell最新文献

{"title":"Featured Cover","authors":"Richie P. Goulding,&nbsp;Braeden T. Charlton,&nbsp;Ellen A. Breedveld,&nbsp;Matthijs van der Laan,&nbsp;Anne R. Strating,&nbsp;Wendy Noort,&nbsp;Aryna Kolodyazhna,&nbsp;Brent Appelman,&nbsp;Michèle van Vugt,&nbsp;Anita E. Grootemaat,&nbsp;Nicole N. van der Wel,&nbsp;Jos J. de Koning,&nbsp;Frank W. Bloemers,&nbsp;Rob C. I. Wüst","doi":"10.1111/acel.70017","DOIUrl":"https://doi.org/10.1111/acel.70017","url":null,"abstract":"<p>Cover legend: The cover image is based on the article Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity by Rob Wüst <i>et al</i>., https://doi.org/10.1111/acel.14386.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397013","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}

{"title":"Correction to “Targeting miR-124/ Ferroportin Signaling Ameliorated Neuronal Cell Death Through Inhibiting Apoptosis and Ferroptosis in Aged Intracerebral Hemorrhage Murine Model”","authors":"","doi":"10.1111/acel.70006","DOIUrl":"10.1111/acel.70006","url":null,"abstract":"<p>Bao, W.-D., X.-T. Zhou, L.-T. Zhou, et al. 2020. “Targeting miR-124/Ferroportin Signaling Ameliorated Neuronal Cell Death Through Inhibiting Apoptosis and Ferroptosis in Aged Intracerebral Hemorrhage Murine Model.” <i>Aging Cell</i> 19: e13235. https://doi.org/10.1111/acel.13235.</p><p>During the data organization of this manuscript, there was an error inadvertently incorporated into the manuscript. We mistakenly placed a duplicated image of iron staining for two control groups: the ICH and con virus group in Figure 2E. All other parts of this article remain intact, valid, and unchanged.</p><p>The authors apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404962","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}

{"title":"Proteasome Augmentation Mitigates Age-Related Cognitive Decline in Mice","authors":"Danitra Parker,&nbsp;Kanisa Davidson,&nbsp;Pawel A. Osmulski,&nbsp;Maria Gaczynska,&nbsp;Andrew M. Pickering","doi":"10.1111/acel.14492","DOIUrl":"10.1111/acel.14492","url":null,"abstract":"<p>The aging brain experiences a significant decline in proteasome function. The proteasome is critical for many key neuronal functions including neuronal plasticity, and memory formation/retention. Treatment with proteasome inhibitors impairs these processes. Our study reveals a marked reduction in 20S and 26S proteasome activities in aged mice brains, including in the hippocampus, this is driven by reduced functionality of aged proteasome. The decline in proteasome activity is matched by a decline in 20S proteasome assembly. In contrast, 26S proteasome assembly was found to increase with age, though 26S proteasome activity was still found to decline. Our data suggests that age-related declines in proteasome activity is driven predominantly by reduced functionality of proteasome rather than altered composition. By overexpressing the proteasome subunit PSMB5 in the neurons of mice to increase the proteasome content and thus enhance its functionality, we slowed age-related declines in spatial learning and memory. We then showed acute treatment with a proteasome activator to rescue spatial learning and memory deficits in aged mice. These findings highlight the potential of proteasome augmentation as a therapeutic strategy to mitigate age-related cognitive declines.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404975","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}

{"title":"RETRACTION: Bmi-1 Plays a Critical Role in Protection From Renal Tubulointerstitial Injury by Maintaining Redox Balance","authors":"","doi":"10.1111/acel.70012","DOIUrl":"10.1111/acel.70012","url":null,"abstract":"<p><b>RETRACTION</b>: J. Jin, X. Lv, L. Chen, W. Zhang, J. Li, Q. Wang, R. Wang, X. Lu, and D. Miao, “Bmi-1 Plays a Critical Role in Protection From Renal Tubulointerstitial Injury by Maintaining Redox Balance,” <i>Aging Cell</i> 13, no. 5 (2014): 797–809, https://doi.org/10.1111/acel.12236.</p><p>The above article, published online on 11 June 2014, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Monty Montano; The Anatomical Society; and John Wiley &amp; Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed image section duplications between this (Figure 3C, WT TNF-α panel) and another article that was subsequently published by an overlapping group of authors, where the image depicts different experimental details. The investigation discovered further image duplications, showing overlapping fields of view between Figure S3G Cortex and Medulla KO panels and between Figure S4C and S4D Medulla KO TNF-α and IL-6 panels. The explanation and the partial raw data shared by the authors was deemed insufficient to fully address these concerns. Thus, the editors have lost confidence in the presented data and decided to retract the article. The authors disagree with the retraction.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404976","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}

{"title":"Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria","authors":"Zhanguo Gao,&nbsp;Yongmei Yu,&nbsp;Kristin Eckel-Mahan,&nbsp;Mikhail G. Kolonin","doi":"10.1111/acel.14499","DOIUrl":"10.1111/acel.14499","url":null,"abstract":"<p>Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO in endothelial or myeloid cells. To characterize the telomere-independent effects of <i>TERT</i> in the APC lineage, we analyzed mice with <i>TERT</i> knockout in mature adipocytes (AD-TERT-KO), which do not proliferate and avoid telomere attrition. Analysis of adipocytes from AD-TERT-KO mice indicated reliance on glycolysis and decreased mitochondrial oxidative metabolism. We show that AD-TERT-KO mice have reduced cold tolerance and metabolism abnormality indicating a defect in adaptive thermogenesis, characteristic of aging. Conversely, ectopic TERT expression in brown adipocytes-induced mitochondrial oxidation and thermogenic gene expression. We conclude that TERT plays an important non-canonical function in the mitochondria of adipocytes.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397710","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}

{"title":"Novel TORC1 inhibitor Ecl1 is regulated by phosphorylation in fission yeast","authors":"Hokuto Ohtsuka,&nbsp;Sawa Kawai,&nbsp;Yurika Ito,&nbsp;Yuka Kato,&nbsp;Takafumi Shimasaki,&nbsp;Kazuki Imada,&nbsp;Yoko Otsubo,&nbsp;Akira Yamashita,&nbsp;Emi Mishiro-Sato,&nbsp;Keiko Kuwata,&nbsp;Hirofumi Aiba","doi":"10.1111/acel.14450","DOIUrl":"10.1111/acel.14450","url":null,"abstract":"<p>Extender of chronological lifespan 1 (Ecl1) inhibits target of rapamycin complex 1 (TORC1) and is necessary for appropriate cellular responses to various stressors, such as starvation, in fission yeast. However, little is known about the effect of posttranslational modifications on Ecl1 regulation. Thus, we investigated the phosphorylation levels of Ecl1 extracted from yeast under conditions of sulfur or metal starvation. Mass spectrometry analysis revealed that Ecl1 was phosphorylated at Thr7, and the level was decreased by starvation. The phosphorylation-mimetic mutation of Thr7 significantly reduced the effects of Ecl1-induced cellular responses to starvation, suggesting that Ecl1 function was suppressed by Thr7 phosphorylation. By contrast, regardless of starvation exposure, TORC1 was significantly suppressed, even when Thr7 phosphorylation-mimetic Ecl1 was overexpressed. This indicated that Ecl1 suppressed TORC1 regardless of Thr7 phosphorylation. We newly identified that Ecl1 physically interacted with TORC1 subunit RAPTOR (Mip1). Based on these evidences, we propose that, Ecl1 has dual functional modes: quantity-dependent TORC1 inhibition and Thr7 phosphorylation–dependent control of cellular function.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254161","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}

{"title":"A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study","authors":"Lisa J. Schmunk,&nbsp;Toby P. Call,&nbsp;Daniel L. McCartney,&nbsp;Hira Javaid,&nbsp;Waylon J. Hastings,&nbsp;Vanja Jovicevic,&nbsp;Dragoljub Kojadinović,&nbsp;Natacha Tomkinson,&nbsp;Eliska Zlamalova,&nbsp;Kirsty C. McGee,&nbsp;Jack Sullivan,&nbsp;Archie Campbell,&nbsp;Andrew M. McIntosh,&nbsp;Veronika Óvári,&nbsp;Karl Wishart,&nbsp;Christian E. Behrens,&nbsp;Emma Stone,&nbsp;Miloš Gavrilov,&nbsp;Rob Thompson,&nbsp;Hurdle bio-infrastructure team,&nbsp;Thomas Jackson,&nbsp;Janet M. Lord,&nbsp;Thomas M. Stubbs,&nbsp;Riccardo E. Marioni,&nbsp;Daniel E. Martin-Herranz","doi":"10.1111/acel.14444","DOIUrl":"10.1111/acel.14444","url":null,"abstract":"<p>Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood proteins (EpiScores). We apply these methods to create a new saliva-based epigenetic clock (InflammAge) that quantifies systemic chronic inflammation (SCI) in humans. Using a large blood DNAm human cohort with linked electronic health records and over 18,000 individuals (Generation Scotland), we demonstrate that InflammAge significantly associates with all-cause mortality, disease outcomes, lifestyle factors, and immunosenescence; in many cases outperforming the widely used SCI biomarker C-reactive protein (CRP). We propose that our biomarker discovery framework and InflammAge will be useful to improve understanding of the molecular mechanisms underpinning human ageing and to assess the impact of gero-protective interventions.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062499","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}

{"title":"Epigenetic modulation rescues neurodevelopmental deficits in Syngap1+/− mice","authors":"Akash Kumar Singh,&nbsp;Ila Joshi,&nbsp;Neeharika M. N. Reddy,&nbsp;Sushmitha S. Purushotham,&nbsp;M. Eswaramoorthy,&nbsp;Madavan Vasudevan,&nbsp;Sourav Banerjee,&nbsp;James P. Clement,&nbsp;Tapas K. Kundu","doi":"10.1111/acel.14408","DOIUrl":"10.1111/acel.14408","url":null,"abstract":"<p>SYNGAP1 is a Ras GTPase-activating protein that plays a crucial role during brain development and in synaptic plasticity. Sporadic heterozygous mutations in <i>SYNGAP1</i> affect social and emotional behaviour observed in intellectual disability (ID) and autism spectrum disorder (ASD). Although neurophysiological deficits have been extensively studied, the epigenetic landscape of <i>SYNGAP1</i> mutation-mediated intellectual disability is unexplored. Here, we have found that the p300/CBP specific acetylation marks of histones are significantly repressed in the hippocampus of adolescent <i>Syngap1</i>^<i>+/−</i> mice. Additionally, we observed decreased dendritic branching of newly born DCX⁺ neurons in these mice, suggesting altered adult hippocampal neurogenesis. To establish the causal relationship of <i>Syngap1</i>^<i>+/−</i> phenotype and the altered histone acetylation signature we have treated 2–4 months old <i>Syngap1</i>^<i>+/−</i> mice with glucose-derived carbon nanosphere (CSP) conjugated potent small molecule activator (TTK21) of p300/CBP lysine acetyltransferase (CSP-TTK21). The enhancement of the p300/CBP specific acetylation marks of histones by CSP-TTK21 restored synaptic functions, increased dendritic branching of DCX⁺ neurons, enables the capability to reorganise cortical circuits in response to change in the sensory stimuli, and improves behavioural measures in <i>Syngap1</i>^<i>+/−</i> mice that are very closely comparable to wild type littermates. Further, hippocampal RNA-Seq analysis of these mice revealed that the expression of many critical genes such as Adcy1, Ntrk3, Egr1, and Foxj1 which are key regulators of synaptic plasticity and neurogenesis and are well associated with ID/ASD reversed upon CSP-TTK21 treatment. This study could be the first demonstration of the reversal of autistic behaviour and neural wiring upon the modulation of altered epigenetic modification(s).</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057563","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}

{"title":"Raman Spectroscopy in Cellular and Tissue Aging Research","authors":"Jeong Hee Kim,&nbsp;Daejong Yang,&nbsp;Seungman Park","doi":"10.1111/acel.14494","DOIUrl":"10.1111/acel.14494","url":null,"abstract":"<p>The establishment of various molecular, physiological, and genetic markers for cellular senescence and aging-associated conditions has progressed the aging study. To identify such markers, a combination of optical, proteomic-, and sequencing-based tools is primarily used, often accompanying extrinsic labels. Yet, the tools for clinical detection at the molecular, cellular, and tissue levels are still lacking which profoundly hinders advancements in the specific detection and timely prevention of aging-related diseases and pathologies. Raman spectroscopy, with its capability for rapid, label-free, and non-invasive analysis of molecular compositions and alterations in aging cells and tissues, holds considerable promise for in vivo applications. In this review, we present recent advancements in the application of Raman spectroscopy to the study of aging in cells and tissues. We explore the use of Raman spectroscopy and related techniques for detecting cellular aging and senescence, focusing on the molecular alterations that accompany these processes. Subsequently, we provide a review of the application of Raman spectroscopy in identifying aging-related changes in various molecules within tissues and organs.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057565","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}

{"title":"Lifetime age-related changes in clinical laboratory results, aging clocks and mortality predictors in 2412 Golden Retrievers","authors":"Kevin Perez,&nbsp;Brenna Swafford,&nbsp;Julia Labadie,&nbsp;Alejandro Ocampo","doi":"10.1111/acel.14438","DOIUrl":"10.1111/acel.14438","url":null,"abstract":"<p>In this study, we investigated age-related changes in clinical laboratory data and their association with mortality in dogs from the Golden Retriever Lifetime Study. By analyzing complete blood count (CBC) and biochemistry data from 2′412 Golden Retrievers over 16,678 visits, we observed significant changes during the first 2 years of life and throughout aging. Based on these observations, we developed a biological aging clock using a LASSO model to predict age based on blood markers, achieving an accuracy of <i>R</i> = 0.78. Although the biological age clock and pace of aging did not significantly improve mortality prediction, a model incorporating all blood biomarkers showed better predictive power for lifetime (C-index = 0.763) and 1-year mortality (AUC = 0.817). Our findings underscore the importance of comprehensive blood analysis for aging and mortality prediction in dogs and open the door for the development of novel methods to investigate aging in companion animals.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031587","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}