Aging Cell最新文献

{"title":"Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort","authors":"Jiachen Chen,&nbsp;Margaret F. Doyle,&nbsp;Yuan Fang,&nbsp;Jesse Mez,&nbsp;Paul K. Crane,&nbsp;Phoebe Scollard,&nbsp;ADSP Data Harmonization Consortium Cognitive Harmonization Core,&nbsp;Claudia L. Satizabal,&nbsp;Michael L. Alosco,&nbsp;Wei Qiao Qiu,&nbsp;Joanne M. Murabito,&nbsp;Kathryn L. Lunetta","doi":"10.1111/acel.13955","DOIUrl":"10.1111/acel.13955","url":null,"abstract":"<p>Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (<i>N</i> = 708, 53% female, 22% apolipoprotein E (<i>APOE</i>) ε4 carriers, 15% <i>APOE</i> ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. <i>APOE</i> genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between <i>APOE</i> ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136439","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":"Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis","authors":"Hasan Ishtayeh,&nbsp;Margarita Galves,&nbsp;Tania T. Barnatan,&nbsp;Yevgeny Berdichevsky,&nbsp;Fatima Amer-Sarsour,&nbsp;Metsada Pasmanik-Chor,&nbsp;Itzhak Braverman,&nbsp;Sergiu C. Blumen,&nbsp;Avraham Ashkenazi","doi":"10.1111/acel.13949","DOIUrl":"10.1111/acel.13949","url":null,"abstract":"<p>Autophagy is an intracellular degradative process with an important role in cellular homeostasis. Here, we show that the RNA binding protein (RBP), heterogeneous nuclear ribonucleoprotein Q (HNRNPQ)/SYNCRIP is required to stimulate early events in autophagosome biogenesis, in particular the induction of VPS34 kinase by ULK1-mediated beclin 1 phosphorylation. The RBPs HNRNPQ and poly(A) binding protein nuclear 1 (PABPN1) form a regulatory network that controls the turnover of distinct autophagy-related (ATG) proteins. We also show that oculopharyngeal muscular dystrophy (OPMD) mutations engender a switch from autophagosome stimulation to autophagosome inhibition by impairing PABPN1 and HNRNPQ control of the level of ULK1. The overexpression of HNRNPQ in OPMD patient-derived cells rescues the defective autophagy in these cells. Our data reveal a regulatory mechanism of autophagy induction that is compromised by PABPN1 disease mutations, and may thus further contribute to their deleterious effects.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13949","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9967194","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":"Anatomical Society Research Studentships 2023/24","authors":"","doi":"10.1111/acel.13956","DOIUrl":"https://doi.org/10.1111/acel.13956","url":null,"abstract":"","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 8","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6147379","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":"Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging","authors":"Yuli Hou,&nbsp;Qiao Song,&nbsp;Yaqi Wang,&nbsp;Jing Liu,&nbsp;Yuting Cui,&nbsp;Xiaomin Zhang,&nbsp;Jingjing Zhang,&nbsp;Jingxuan Fu,&nbsp;Min Cao,&nbsp;Chi Zhang,&nbsp;Congcong Liu,&nbsp;Xiaoling Wang,&nbsp;Huanli Duan,&nbsp;Peichang Wang","doi":"10.1111/acel.13950","DOIUrl":"10.1111/acel.13950","url":null,"abstract":"<p>Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether Krüppel-like factor 14 (KLF14) is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging-related pathologies in C57BL/6J mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1 expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging-related pathologies in senescence-accelerated P8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14's transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging-associated diseases.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13950","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9945367","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":"Decoding of translation-regulating entities reveals heterogeneous translation deficiency patterns in cellular senescence","authors":"Angelos Papaspyropoulos,&nbsp;Orsalia Hazapis,&nbsp;Abdullah Altulea,&nbsp;Aikaterini Polyzou,&nbsp;Panayotis Verginis,&nbsp;Konstantinos Evangelou,&nbsp;Maria Fousteri,&nbsp;Argyris Papantonis,&nbsp;Marco Demaria,&nbsp;Vassilis Gorgoulis","doi":"10.1111/acel.13893","DOIUrl":"https://doi.org/10.1111/acel.13893","url":null,"abstract":"<p>Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). These senescence subtypes are heterogeneous and often develop subset-specific phenotypes. Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery between senescence subsets.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6817972","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":"Alterations of SIRT1/SIRT3 subcellular distribution in aging undermine cardiometabolic homeostasis during ischemia and reperfusion","authors":"Jingwen Zhang,&nbsp;Hao Wang,&nbsp;Lily Slotabec,&nbsp;Feng Cheng,&nbsp;Yi Tan,&nbsp;Ji Li","doi":"10.1111/acel.13930","DOIUrl":"https://doi.org/10.1111/acel.13930","url":null,"abstract":"<p>Age-related sensors Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) play an essential role in the protective response upon myocardial ischemia and/or reperfusion (I/R). However, the subcellular localization and co-regulatory network between cardiac SIRT1 and SIRT3 remain unknown, especially their effects on age-related metabolic regulation during acute ischemia and I/R. Here, we found that defects of cardiac SIRT1 or SIRT3 with aging result in an exacerbated cardiac physiological structural and functional deterioration after acute ischemic stress and failed recovery through reperfusion operation. In aged hearts, SIRT1 translocated into mitochondria and recruited more mitochondria SIRT3 to enhance their interaction during acute ischemia, acting as adaptive protection for the aging hearts from further mitochondria dysfunction. Subsequently, SIRT3-targeted proteomics revealed that SIRT1 plays a crucial role in maintaining mitochondrial integrity through SIRT3-mediated substrate metabolism during acute ischemic and I/R stress. Although the loss of SIRT1/SIRT3 led to a compromised PGC-1α/PPARα-mediated transcriptional control of fatty acid oxidation in response to acute ischemia and I/R, their crosstalk in mitochondria plays a more important role in the aging heart during acute ischemia. However, the increased mitochondria SIRT1-SIRT3 interaction promoted adaptive protection to aging-related fatty acid metabolic disorder via deacetylation of long-chain acyl CoA dehydrogenase (LCAD) during ischemic insults. Therefore, the dynamic network of SIRT1/SIRT3 acts as a mediator that regulates adaptive metabolic response to improve the tolerance of aged hearts to ischemic insults, which will facilitate investigation into the role of SIRT1/SIRT3 in age-related ischemic heart disease.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13930","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6777600","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":"Erratum to: Increased miR-34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS-JNK-p53 pathway in Alzheimer's disease","authors":"","doi":"10.1111/acel.13933","DOIUrl":"https://doi.org/10.1111/acel.13933","url":null,"abstract":"<p>Shi, Z, Zhang, K, Zhou, H, et al. Increased miR-34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS-JNK-p53 pathway in Alzheimer's Disease. <i>Aging Cell</i>. 2020; 19:e13125. https://doi.org/10.1111/acel.13125</p><p>In the published version of Shi, et al. (2020), the titles of the vertical coordinates of Figure 5(b) and (c) were interchanged, the revised version of Figure 5 and its caption is shown below:</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6753009","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":"Glycogen phosphorylase inhibition improves cognitive function of aged mice","authors":"Dominika Drulis-Fajdasz,&nbsp;Adam Krzystyniak,&nbsp;Alicja Pu?cian,&nbsp;Agata Pyty?,&nbsp;Kinga Gostomska-Pampuch,&nbsp;Natalia Pude?ko-Malik,&nbsp;Jerzy ?. Wi?niewski,&nbsp;Piotr M?ynarz,&nbsp;Arkadiusz Miazek,&nbsp;Tomasz Wójtowicz,&nbsp;Jakub W?odarczyk,&nbsp;Kamila Du?-Szachniewicz,&nbsp;Agnieszka Gizak,&nbsp;Jacek R. Wi?niewski,&nbsp;Dariusz Rakus","doi":"10.1111/acel.13928","DOIUrl":"https://doi.org/10.1111/acel.13928","url":null,"abstract":"<p>Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of memory formation, in hippocampal slices of old animals. Here, we report that a 2-week treatment with glycogen phosphorylase inhibitor BAY U6751 alleviated memory deficits and stimulated neuroplasticity in old mice. Using the 2-Novel Object Recognition and Novel Object Location tests, we discovered that the prolonged intraperitoneal administration of BAY U6751 improved memory formation in old mice. This was accompanied by changes in morphology of dendritic spines in hippocampal neurons, and by “rejuvenation” of hippocampal proteome. In contrast, in young animals, inhibition of glycogen degradation impaired memory formation; however, as in old mice, it did not alter significantly the morphology and density of cortical dendritic spines. Our findings provide evidence that prolonged inhibition of glycogen phosphorolysis improves memory formation of old animals. This could lead to the development of new strategies for treatment of age-related memory deficits.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7069053","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":"Corrigendum to: Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: Involvement of RhoA/ROCK2 pathway","authors":"","doi":"10.1111/acel.13945","DOIUrl":"10.1111/acel.13945","url":null,"abstract":"<p>Zhu, Z., Lu, J., Wang, S., Peng, W., Yang, Y., Chen, C., Zhou, X., Yang, X., Xin, W., Chen, X., Pi, J., Yin, W., Yao, L., &amp; Pi, R. (2022). Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: Involvement of RhoA/ROCK2 pathway. <i>Aging Cell</i>, 21, e13587. https://doi.org/10.1111/acel.13587</p><p><b>FIGURE 2</b>. Acrolein induced synaptic rupture in vivo by using Golgi-Cox staining. The mice were treated with acrolein (3.0 mg/kg/day) or with distilled water for 1–8 weeks. After all behavior tests, the mice were scarified and their brain tissues were harvested for GolgiCox staining and Western blot assay. (A) (a–c) The photographs of synapses in hippocampus and cortex were taken by phase contrast microscopy, cortex: 10× (a), 20× (b) and hippocampus: 40× (c). (d) Quantitative analysis of the dendrites. (B) Representative images of proteins reflecting synaptic functional expression (PSD95, SV2a, Synapsin1) in the hippocampus and cortex using western blot analysis. The data were expressed as mean ± SEM, <i>n</i> = 3 *<i>p</i> &lt; 0.05, **<i>p</i> &lt; 0.01 versus control group.</p><p>We apologize for these errors.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13945","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895065","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":"Fibroblast growth factor 10 ameliorates neurodegeneration in mouse and cellular models of Alzheimer's disease via reducing tau hyperphosphorylation and neuronal apoptosis","authors":"Kaiming Guo,&nbsp;Wenting Huang,&nbsp;Kun Chen,&nbsp;Pengkai Huang,&nbsp;Wenshuo Peng,&nbsp;Ruiqing Shi,&nbsp;Tao He,&nbsp;Mulan Zhang,&nbsp;Hao Wang,&nbsp;Jian Hu,&nbsp;Xinshi Wang,&nbsp;Yangping Shentu,&nbsp;Huiqin Xu,&nbsp;Li Lin","doi":"10.1111/acel.13937","DOIUrl":"https://doi.org/10.1111/acel.13937","url":null,"abstract":"<p>Alzheimer's disease (AD) is characterized with senile plaques formed by Aβ deposition, and neurofibrillary tangles composed of hyperphosphorylated tau protein, which ultimately lead to cognitive impairment. Despite the heavy economic and life burdens faced by the patients with AD, effective treatments are still lacking. Previous studies have reported the neuroprotective effects of FGF10 in CNS diseases, but its role in AD remains unclear. In this study, we demonstrated that FGF10 levels were reduced in the serum of AD patients, as well as in the brains of 3xTg-AD mice and APPswe-transfected HT22 cells, suggesting a close relationship between FGF10 and AD. Further investigations revealed that intranasal delivery of FGF10 improved cognitive functions in 3xTg-AD mice. Additionally, FGF10 treatment reduced tau hyperphosphorylation and neuronal apoptosis, thereby mitigating neuronal cell damage and synaptic deficits in the cortex and hippocampus of 3xTg-AD mice, as well as APPswe-transfected HT22 cells. Furthermore, we evaluated the therapeutic potential of FGF10 gene delivery for treating AD symptoms and pathologies. Tail vein delivery of the FGF10 gene using AAV9 improved cognitive and neuronal functions in 3xTg-AD mice. Similarly, endogenous FGF10 overexpression ameliorated tau hyperphosphorylation and neuronal apoptosis in the cortex and hippocampus of 3xTg-AD mice. Importantly, we confirmed that the FGFR2/PI3K/AKT signaling pathway was activated following intranasal FGF10 delivery and AAV9-mediated FGF10 gene delivery in 3xTg-AD mice and APPswe-transfected HT22 cells. Knockdown of FGFR2 attenuated the protective effect of FGF10. Collectively, these findings suggest that intranasal delivery of FGF10 and AAV9-mediated FGF10 gene delivery could be a promising disease-modifying therapy for AD.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 9","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13937","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"7043494","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}