Aging Cell最新文献_第3页

Anatomical Society Research Studentships 2024/25 解剖学会 2024/25 年度研究奖学金

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-19 DOI: 10.1111/acel.14274

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IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-19 DOI: 10.1111/acel.14280

Karolis Koncevičius, Akhil Nair, Aušrinė Šveikauskaitė, Agnė Šeštokaitė, Auksė Kazlauskaitė, Audrius Dulskas, Artūras Petronis

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IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-19 DOI: 10.1111/acel.14279

Solal Chauquet, Emily F. Willis, Laura Grice, Samuel B. R. Harley, Joseph E. Powell, Naomi R. Wray, Quan Nguyen, Marc J. Ruitenberg, Sonia Shah, Jana Vukovic

引用次数: 0

The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway SASP因子IL-6通过cGAS-STING-NFκB内分泌衰老非典型途径维持细胞自主衰老细胞。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-16 DOI: 10.1111/acel.14258

Florencia Herbstein, Melanie Sapochnik, Alejandra Attorresi, Cora Pollak, Sergio Senin, David Gonilski-Pacin, Nicolas Ciancio del Giudice, Manuel Fiz, Belén Elguero, Mariana Fuertes, Lara Müller, Marily Theodoropoulou, Lucas B. Pontel, Eduardo Arzt

{"title":"The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway","authors":"Florencia Herbstein, Melanie Sapochnik, Alejandra Attorresi, Cora Pollak, Sergio Senin, David Gonilski-Pacin, Nicolas Ciancio del Giudice, Manuel Fiz, Belén Elguero, Mariana Fuertes, Lara Müller, Marily Theodoropoulou, Lucas B. Pontel, Eduardo Arzt","doi":"10.1111/acel.14258","DOIUrl":"10.1111/acel.14258","url":null,"abstract":"Senescent cells produce a Senescence-Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin-6 (IL-6), has the potential to amplify cellular senescence in the SASP-producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear. We found that the senescence action does not involve IL-6 secretion nor the interaction with the receptor expressed in the membrane but is amplified through an intracrine mechanism. IL-6 sustains intracrine senescence interacting with the intracellular IL-6 receptor located in anterograde traffic specialized structures, with cytosolic DNA, cGAS-STING, and NFκB activation. This pathway triggered by intracellular IL-6 significantly contributes to cell-autonomous induction of senescence and impacts in tumor growth control. Inactivation of IL-6 in somatotrophic senescent cells transforms them into strongly tumorigenic in NOD/SCID mice, while re-expression of IL-6 restores senescence control of tumor growth. The intracrine senescent IL-6 pathway is further evidenced in three human cellular models of therapy-induced senescence. The compartmentalization of the intracellular signaling, in contrast to the paracrine tumorigenic action, provides a pathway for IL-6 to sustain cell-autonomous senescent cells, driving the SASP, and opens new avenues for clinical consideration to senescence-based therapies.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease 髓系异位病毒整合位点 2 加速了阿尔茨海默病的进展。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-12 DOI: 10.1111/acel.14260

Yuting Cui, Xiaomin Zhang, Jing Liu, Yuli Hou, Qiao Song, Min Cao, Jingjing Zhang, Xiaoling Wang, Congcong Liu, Peichang Wang, Yaqi Wang

{"title":"Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease","authors":"Yuting Cui, Xiaomin Zhang, Jing Liu, Yuli Hou, Qiao Song, Min Cao, Jingjing Zhang, Xiaoling Wang, Congcong Liu, Peichang Wang, Yaqi Wang","doi":"10.1111/acel.14260","DOIUrl":"10.1111/acel.14260","url":null,"abstract":"Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-β production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice 转录组和代谢组的变化可预测 SAMP8 小鼠的虚弱程度。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-03 DOI: 10.1111/acel.14263

Letizia Dacomo, Pietro La Vitola, Laura Brunelli, Letizia Messa, Edoardo Micotti, Luisa Artioli, Elena Sinopoli, Greta Cecutti, Susanna Leva, Stella Gagliardi, Orietta Pansarasa, Stephana Carelli, Antonio Guaita, Roberta Pastorelli, Gianluigi Forloni, Cristina Cereda, Claudia Balducci

{"title":"Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice","authors":"Letizia Dacomo, Pietro La Vitola, Laura Brunelli, Letizia Messa, Edoardo Micotti, Luisa Artioli, Elena Sinopoli, Greta Cecutti, Susanna Leva, Stella Gagliardi, Orietta Pansarasa, Stephana Carelli, Antonio Guaita, Roberta Pastorelli, Gianluigi Forloni, Cristina Cereda, Claudia Balducci","doi":"10.1111/acel.14263","DOIUrl":"10.1111/acel.14263","url":null,"abstract":"Frailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation SCARF2 是慢性阻塞性肺病的靶点：多组学研究和队列验证的证据

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-03 DOI: 10.1111/acel.14266

Sai Wang, Yuanyi Yue, Xueqing Wang, Yue Tan, Qiang Zhang

{"title":"SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation","authors":"Sai Wang, Yuanyi Yue, Xueqing Wang, Yue Tan, Qiang Zhang","doi":"10.1111/acel.14266","DOIUrl":"10.1111/acel.14266","url":null,"abstract":"Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome-wide meta-analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome-wide and proteome-wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single-cell transcriptome analysis was performed to link targets with cell types. Individual-level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically-elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome-wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single-cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac and skeletal muscle manifestations in the G608G mouse model of Hutchinson-Gilford progeria syndrome 哈钦森-吉尔福特早衰综合征 G608G 小鼠模型的心脏和骨骼肌表现。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-03 DOI: 10.1111/acel.14259

Yeojin Hong, Alice Rannou, Nancy Manriquez, Jack Antich, Weixin Liu, Mario Fournier, Ariel Omidfar, Russell G. Rogers

{"title":"Cardiac and skeletal muscle manifestations in the G608G mouse model of Hutchinson-Gilford progeria syndrome","authors":"Yeojin Hong, Alice Rannou, Nancy Manriquez, Jack Antich, Weixin Liu, Mario Fournier, Ariel Omidfar, Russell G. Rogers","doi":"10.1111/acel.14259","DOIUrl":"10.1111/acel.14259","url":null,"abstract":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder resulting from de novo mutations in the lamin A gene. Children with HGPS typically pass away in their teenage years due to cardiovascular diseases such as atherosclerosis, myocardial infarction, heart failure, and stroke. In this study, we characterized the G608G HGPS mouse model and explored cardiac and skeletal muscle function, along with senescence-associated phenotypes in fibroblasts. Homozygous G608G HGPS mice exhibited cardiac dysfunction, including decreased cardiac output and stroke volume, and impaired left ventricle relaxation. Additionally, skeletal muscle exhibited decreased isometric tetanic torque, muscle atrophy, and increased fibrosis. HGPS fibroblasts showed nuclear abnormalities, decreased proliferation, and increased expression of senescence markers. These findings provide insights into the pathophysiology of the G608G HGPS mouse model and inform potential therapeutic strategies for HGPS.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accumulation of DNA G-quadruplex in mitochondrial genome hallmarks mesenchymal senescence 线粒体基因组中DNA G-四联体的积累是间质衰老的标志。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-02 DOI: 10.1111/acel.14265

Kangkang Yu, Feifei Li, Ling Ye, Fanyuan Yu

{"title":"Accumulation of DNA G-quadruplex in mitochondrial genome hallmarks mesenchymal senescence","authors":"Kangkang Yu, Feifei Li, Ling Ye, Fanyuan Yu","doi":"10.1111/acel.14265","DOIUrl":"10.1111/acel.14265","url":null,"abstract":"Searching for biomarkers of senescence remains necessary and challenging. Reliable and detectable biomarkers can indicate the senescence condition of individuals, the need for intervention in a population, and the effectiveness of that intervention in controlling or delaying senescence progression and senescence-associated diseases. Therefore, it is of great importance to fulfill the unmet requisites of senescence biomarkers especially when faced with the growing global senescence nowadays. Here, we established that DNA G-quadruplex (G4) in mitochondrial genome was a reliable hallmark for mesenchymal senescence. Via developing a versatile and efficient mitochondrial G4 (mtG4) probe we revealed that in multiple types of senescence, including chronologically healthy senescence, progeria, and replicative senescence, mtG4 hallmarked aged mesenchymal stem cells. Furthermore, we revealed the underlying mechanisms by which accumulated mtG4, specifically within respiratory chain complex (RCC) I and IV loci, repressed mitochondrial genome transcription, finally impairing mitochondrial respiration and causing mitochondrial dysfunction. Our findings endowed researchers with the visible senescence biomarker based on mitochondrial genome and furthermore revealed the role of mtG4 in inhibiting RCC genes transcription to induce senescence-associated mitochondrial dysfunction. These findings depicted the crucial roles of mtG4 in predicting and controlling mesenchymal senescence.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity 线粒体裂变或线粒体融合基因的过度表达可增强复原能力并延长寿命。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-07-02 DOI: 10.1111/acel.14262

Annika Traa, Allison Keil, Abdelrahman AlOkda, Suleima Jacob-Tomas, Aura A. Tamez González, Shusen Zhu, Zenith Rudich, Jeremy M. Van Raamsdonk

{"title":"Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity","authors":"Annika Traa, Allison Keil, Abdelrahman AlOkda, Suleima Jacob-Tomas, Aura A. Tamez González, Shusen Zhu, Zenith Rudich, Jeremy M. Van Raamsdonk","doi":"10.1111/acel.14262","DOIUrl":"10.1111/acel.14262","url":null,"abstract":"The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected, and well-organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age-associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp-1 or the mitochondrial fusion genes fzo-1 and eat-3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance, and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which in the case of the mitochondrial fusion overexpression strains appears to be at least partially due to the upregulation of multiple pathways of cellular resilience in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0