Aging Cell最新文献

{"title":"HIF-1α-induced expression of the m6A reader YTHDF1 inhibits the ferroptosis of nucleus pulposus cells by promoting SLC7A11 translation","authors":"Xiao Lu,&nbsp;Dachuan Li,&nbsp;Zhidi Lin,&nbsp;Tian Gao,&nbsp;Zhaoyang Gong,&nbsp;Yuxuan Zhang,&nbsp;Hongli Wang,&nbsp;Xinlei Xia,&nbsp;Feizhou Lu,&nbsp;Jian Song,&nbsp;Guangyu Xu,&nbsp;Jianyuan Jiang,&nbsp;Xiaosheng Ma,&nbsp;Fei Zou","doi":"10.1111/acel.14210","DOIUrl":"10.1111/acel.14210","url":null,"abstract":"<p>The nucleus pulposus is in a hypoxic environment in the human body, and when intervertebral disc degeneration (IVDD) occurs, the hypoxic environment is disrupted. Nucleus pulposus cell (NPC) ferroptosis is one of the causes of IVDD. N6-methyladenosine (m6A) and its reader protein YTHDF1 regulate cellular activities by affecting RNA metabolism. However, the regulation of ferroptosis in NPCs by m6A-modified RNAs under hypoxic conditions has not been as well studied. In this study, through in vitro and in vivo experiments, we explored the underlying mechanism of HIF-1α and YTHDF1 in regulating ferroptosis in NPCs. The results indicated that the overexpression of HIF-1α or YTHDF1 suppressed NPC ferroptosis; conversely, the knockdown of HIF-1α or YTHDF1 increased ferroptosis levels in NPCs. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region. Polysome profiling results showed that YTHDF1 promoted the translation of SLC7A11 and consequently the expression of the anti-ferroptosis protein GPX4 by binding to m6A-modified SLC7A11 mRNA. In conclusion, HIF-1α-induced YTHDF1 expression reduces NPC ferroptosis and delays IVDD by promoting SLC7A11 translation in a m6A-dependent manner.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085954","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 2024/25","authors":"","doi":"10.1111/acel.14213","DOIUrl":"https://doi.org/10.1111/acel.14213","url":null,"abstract":"","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085115","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":"Additional Cover","authors":"Sushil K. Dubey,&nbsp;Rashmi Dubey,&nbsp;Subhash C. Prajapati,&nbsp;Kyungsik Jung,&nbsp;Kabhilan Mohan,&nbsp;Xinan Liu,&nbsp;Jacob Roney,&nbsp;Wenjian Tian,&nbsp;Jennifer Abney,&nbsp;Michelle M. Giarmarco,&nbsp;Alvaro G. Hernandez,&nbsp;Jinze Liu,&nbsp;Mark E. Kleinman","doi":"10.1111/acel.14233","DOIUrl":"https://doi.org/10.1111/acel.14233","url":null,"abstract":"<p>Cover legend: The cover image is based on the Research Article <i>Histone deficiency and hypoacetylation in the aging retinal pigment epithelium</i> by Sushil K. Dubey et al., https://doi.org/10.1111/acel.14108 Image Credit: Created with BioRender.com\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":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141084969","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":"Nrf2 activation by pyrroloquinoline quinone inhibits natural aging-related intervertebral disk degeneration in mice","authors":"Qi Xue,&nbsp;Jie Li,&nbsp;Ran Qin,&nbsp;Mingying Li,&nbsp;Yiping Li,&nbsp;Jing Zhang,&nbsp;Rong Wang,&nbsp;David Goltzman,&nbsp;Dengshun Miao,&nbsp;Renlei Yang","doi":"10.1111/acel.14202","DOIUrl":"10.1111/acel.14202","url":null,"abstract":"<p>Age-related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound with strong anti-oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging-related IVDD, and the underlying mechanism. Here, we found that dietary PQQ supplementation for 12 months alleviated IVDD phenotypes in aged mice, including increased disk height index and reduced histological scores and cell loss, without toxicity. Mechanistically, PQQ inhibited oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the nucleus pulposus and annulus fibrosus of aged mice. Similarly, PQQ protected against interleukin-1β-induced matrix degradation, reactive oxygen species accumulation, and senescence in human nucleus pulposus cells (NPCs) in vitro. Molecular docking predicted and biochemical assays validated that PQQ interacts with specific residues to dissociate the Keap1–Nrf2 complex, thereby increasing nuclear Nrf2 translocation and activation of Nrf2-ARE signaling. RNA sequencing and luciferase assays revealed Nrf2 can transcriptionally upregulate Wnt5a by binding to its promoter, while Wnt5a knockdown prevented PQQ inhibition of matrix metalloproteinase-13 in NPCs. Notably, PQQ supplementation failed to alleviate aging-associated IVDD phenotypes and oxidative stress in aged Nrf2 knockout mice, indicating Nrf2 is indispensable for PQQ bioactivities. Collectively, this study demonstrates Nrf2 activation by PQQ inhibits aging-induced IVDD by attenuating cellular senescence and matrix degradation. This study clarifies Keap1–Nrf2–Wnt5a axis as the novel signaling underlying the protective effects of PQQ against aging-related IVDD, and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging-induced IVDD.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080046","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":"Additional Cover","authors":"Charles E. Norton,&nbsp;Rebecca L. Shaw,&nbsp; Safa,&nbsp;Beyoncé Dockery,&nbsp;Timothy L. Domeier,&nbsp;Steven S. Segal","doi":"10.1111/acel.14234","DOIUrl":"https://doi.org/10.1111/acel.14234","url":null,"abstract":"<p>Cover legend: The cover image is based on the Research Article <i>Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress</i> by Charles E. Norton et al., https://doi.org/10.1111/acel.14110\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":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085113","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":"Featured Cover","authors":"Xianwen Shang,&nbsp;Jiahao Liu,&nbsp;Zhuoting Zhu,&nbsp;Xueli Zhang,&nbsp;Yu Huang,&nbsp;Shunming Liu,&nbsp;Wei Wang,&nbsp;Xiayin Zhang,&nbsp;Shuo Ma,&nbsp;Shulin Tang,&nbsp;Yijun Hu,&nbsp;Zongyuan Ge,&nbsp;Honghua Yu,&nbsp;Mingguang He","doi":"10.1111/acel.14232","DOIUrl":"https://doi.org/10.1111/acel.14232","url":null,"abstract":"<p>Cover legend: The cover image is based on the Research Article <i>Metabolomic age and risk of 50 chronic diseases in community-dwelling adults: A prospective cohort study</i> by Xianwen Shang et al., https://doi.org/10.1111/acel.14125<figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085116","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":"Tho2-mediated escort of Nrd1 regulates the expression of aging-related genes","authors":"Yan Liu,&nbsp;Jeong-Min Park,&nbsp;Suji Lim,&nbsp;Ruxin Duan,&nbsp;Do Yoon Lee,&nbsp;Dahee Choi,&nbsp;Dong Kyu Choi,&nbsp;Byung-Ho Rhie,&nbsp;Soo Young Cho,&nbsp;Hong-Yeoul Ryu,&nbsp;Seong Hoon Ahn","doi":"10.1111/acel.14203","DOIUrl":"10.1111/acel.14203","url":null,"abstract":"<p>The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in <i>hpr1Δ</i> or <i>tho2Δ</i> mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in <i>hpr1Δ</i>. However, RLS impairment in <i>hpr1Δ</i> or <i>tho2Δ</i> was counteracted by the additional expression of Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, <i>Tho2</i> deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Furthermore, our genome-wide ChIP-seq analysis revealed an increase in the recruitment of Nrd1 to translation-associated genes, known to be related to aging, upon Tho2 loss. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in the regulation of lifespan pathway through transcriptional regulation of aging-related genes.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070069","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":"Centenarian hippocampus displays high levels of astrocytic metallothioneins","authors":"Ander Saenz-Antoñanzas,&nbsp;Maider Muñoz-Culla,&nbsp;Piero Rigo,&nbsp;Leire Ruiz-Barreiro,&nbsp;Manuel Moreno-Valladares,&nbsp;Ainhoa Alberro,&nbsp;Sara Cruces-Salguero,&nbsp;Marta Arroyo-Izaga,&nbsp;Amaia M. Arranz,&nbsp;David Otaegui,&nbsp;François Guillemot,&nbsp;Ander Matheu","doi":"10.1111/acel.14201","DOIUrl":"10.1111/acel.14201","url":null,"abstract":"<p>The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases. We performed transcriptomic studies in hippocampus samples from individuals of different ages (centenarians [≥97 years], old, and young) and identified a differential gene expression pattern in centenarians compared to the other two groups. In particular, several isoforms of metallothioneins (MTs) were highly expressed in centenarians. Moreover, we identified that MTs were mainly expressed in astrocytes. Functional studies in human primary astrocytes revealed that MT1 and MT3 are necessary for their homeostasis maintenance. Overall, these results indicate that the expression of MTs specifically in astrocytes is a mechanism for protection during aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070066","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":"Accumulation of senescent cells in the adrenal gland induces hypersecretion of corticosterone via IL1β secretion","authors":"Noriyuki Okudaira,&nbsp;Mi-Ho Akimoto,&nbsp;Takao Susa,&nbsp;Miho Akimoto,&nbsp;Harumi Hisaki,&nbsp;Masayoshi Iizuka,&nbsp;Hiroko Okinaga,&nbsp;Julio A. Almunia,&nbsp;Noboru Ogiso,&nbsp;Tomoki Okazaki,&nbsp;Mimi Tamamori-Adachi","doi":"10.1111/acel.14206","DOIUrl":"10.1111/acel.14206","url":null,"abstract":"<p>Aging progresses through the interaction of metabolic processes, including changes in the immune and endocrine systems. Glucocorticoids (GCs), which are regulated by the hypothalamic–pituitary–adrenal (HPA) axis, play an important role in regulating metabolism and immune responses. However, the age-related changes in the secretion mechanisms of GCs remain elusive. Here, we found that corticosterone (CORT) secretion follows a circadian rhythm in young mice, whereas it oversecreted throughout the day in aged mice &gt;18 months old, resulting in the disappearance of diurnal variation. Furthermore, senescent cells progressively accumulated in the zF of the adrenal gland as mice aged beyond 18 months. This accumulation was accompanied by an increase in the number of Ad4BP/SF1 (SF1), a key transcription factor, strongly expressing cells (SF1-high positive: HP). Removal of senescent cells with senolytics, dasatinib, and quercetin resulted in the reduction of the number of SF1-HP cells and recovery of CORT diurnal oscillation in 24-month-old mice. Similarly, administration of a neutralizing antibody against IL1β, which was found to be strongly expressed in the adrenocortical cells of the zF, resulted in a marked decrease in SF1-HP cells and restoration of the CORT circadian rhythm. Our findings suggest that the disappearance of CORT diurnal oscillation is a characteristic of aging individuals and is caused by the secretion of IL1β, one of the SASPs, from senescent cells that accumulate in the zF of the adrenal cortex. These findings provide a novel insight into aging. Age-related hypersecretory GCs could be a potential therapeutic target for aging-related diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070063","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":"Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart","authors":"D. Maggiorani,&nbsp;Y. Santin,&nbsp;K. Formoso,&nbsp;E. Drapé,&nbsp;H. Martini,&nbsp;S. Brun,&nbsp;G. Cousin,&nbsp;O. Lairez,&nbsp;F. Lezoualc'h,&nbsp;A. Parini,&nbsp;V. Douin-Echinard,&nbsp;J. Mialet-Perez","doi":"10.1111/acel.14204","DOIUrl":"10.1111/acel.14204","url":null,"abstract":"<p>The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers. Cardiomyocytes undergo post-mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53-dependent pathway in stress-induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin-treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell-type specific senescence in age-associated cardiac diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954722","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}