Aging Cell最新文献

{"title":"Organellar quality control crosstalk in aging-related disease: Innovation to pave the way","authors":"Yu Li,&nbsp;Jinxin Qi,&nbsp;Linhong Guo,&nbsp;Xian Jiang,&nbsp;Gu He","doi":"10.1111/acel.14447","DOIUrl":"10.1111/acel.14447","url":null,"abstract":"<p>Organellar homeostasis and crosstalks within a cell have emerged as essential regulatory and determining factors for the survival and functions of cells. In response to various stimuli, cells can activate the organellar quality control systems (QCS) to maintain homeostasis. Numerous studies have demonstrated that dysfunction of QCS can lead to various aging-related diseases such as neurodegenerative, pulmonary, cardiometabolic diseases and cancers. However, the interplay between QCS and their potential role in these diseases are poorly understood. In this review, we present an overview of the current findings of QCS and their crosstalk, encompassing mitochondria, endoplasmic reticulum, Golgi apparatus, ribosomes, peroxisomes, lipid droplets, and lysosomes as well as the aberrant interplays among these organelles that contributes to the onset and progression of aging-related disorders. Furthermore, potential therapeutic approaches based on these quality control interactions are discussed. Our perspectives can enhance insights into the regulatory networks underlying QCS and the pathology of aging and aging-related diseases, which may pave the way for the development of novel therapeutic targets.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816701","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":"Ken-ichi Takayama,&nbsp;Takashi Suzuki,&nbsp;Kaoru Sato,&nbsp;Yuko Saito,&nbsp;Satoshi Inoue","doi":"10.1111/acel.14456","DOIUrl":"https://doi.org/10.1111/acel.14456","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>Cooperative nuclear action of RNA-binding proteins PSF and G3BP2 to sustain neuronal cell viability is decreased in aging and\u0000dementia</i> by Satoshi Inoue et al., https://doi.org/10.1111/acel.14316.\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":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868351","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":"Wenwen Ren,&nbsp;Weihao Li,&nbsp;Xudong Cha,&nbsp;Shenglei Wang,&nbsp;Boyu Cai,&nbsp;Tianyu Wang,&nbsp;Fengzhen Li,&nbsp;Tengfei Li,&nbsp;Yingqi Xie,&nbsp;Zengyi Xu,&nbsp;Zhe Wang,&nbsp;Huanhai Liu,&nbsp;Yiqun Yu","doi":"10.1111/acel.14455","DOIUrl":"https://doi.org/10.1111/acel.14455","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>Single-cell transcriptomic atlas of taste papilla aging</i> by Yiqun Yu et al., https://doi.org/10.1111/acel.14308.\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":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868350","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":"Kavita Singh,&nbsp;Shraddha I. Khairnar,&nbsp;Akshay Sanghavi,&nbsp;Tanuja T. Yadav,&nbsp;Neha Gupta,&nbsp;Jay Arora,&nbsp;Harold L. Katcher","doi":"10.1111/acel.14454","DOIUrl":"https://doi.org/10.1111/acel.14454","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>E5 treatment showing improved health-span and lifespan in old Sprague Dawley rats</i> by Kavita Singh et al.,\u0000https://doi.org/10.1111/acel.14335.\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":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868349","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":"Aging research from bench to bedside and beyond: What we learned from Sammy Basso","authors":"Giovanna Lattanzi,&nbsp;Chiara Lanzuolo,&nbsp;Eleonora Cugudda,&nbsp;Lorenzo Maggi,&nbsp;Luisa Politano,&nbsp;Olaya Santiago-Fernández,&nbsp;Giulia Ricci,&nbsp;Stefano Squarzoni,&nbsp;Carlos Lopez-Otin,&nbsp;the Italian Network for Laminopathies","doi":"10.1111/acel.14414","DOIUrl":"10.1111/acel.14414","url":null,"abstract":"&lt;p&gt;Since his teenage years, Sammy demonstrated an extraordinary awareness of his condition, far surpassing the self-awareness of many adults. With his innate positivity, he led a fulfilling life, achieving numerous goals, inspiring both patients and researchers alike. We witnessed him discuss progeria with the same rigor as any other researcher, we saw him working to understand molecular mechanisms in experimental models and clinical presentations in patients, with the final aim to find a cure. Even when discussing the prospect of a cure that hardly could have been found in a few years, he remained focused on younger patients, often stating: “I'm working for them”.&lt;/p&gt;&lt;p&gt;In 2017, he wrote a message intended to be read at his funeral, expressing his thoughts on living with progeria and his positive outlook on life: “&lt;i&gt;I don't know when or how I will leave this world, and many may say that I have lost my battle against the disease. Don't listen to them! There was never a battle to fight; there was only a life to embrace as it is, challenging yet beautiful and extraordinary. There is no reward, no punishment, just a gift by God&lt;/i&gt;” and “&lt;i&gt;If you'd like to remember me, don't waste too much time on various rituals, pray, of course, but also take some glasses, toast to my health and yours, and embrace joy. I've always enjoyed being around others, and that's how I'd like to be remembered&lt;/i&gt;”.&lt;/p&gt;&lt;p&gt;In the last decade, Sammy emerged as one of the most effective science communicators among young people and non-expert audiences worldwide. Together with the American Progeria Research Foundation (https://www.progeriaresearch.org/) he brought tremendous mediatic attention to this rare disease, facilitating the diagnosis of several children worldwide. His speeches raised interest in progeroid rare diseases and fostered a positive attitude towards the challenges living with progeria presents in life and life itself.&lt;/p&gt;&lt;p&gt;One of Sammy's dreams materialized with the establishment of the Italian Network for Laminopathies (NIL) in 2009 (https://www.igm.cnr.it/laminopatie/en/). At the age of 14 years, he was among the founders of NIL, and since then, Sammy and his association, the AIProSaB (https://www.aiprosab.org/), have encouraged all NIL partners to become increasingly engaged, providing motivation and support in various aspects, from data sharing to project drafting, from meeting organization to website development, his last impressive contribution.&lt;/p&gt;&lt;p&gt;As a researcher, Sammy was deeply committed to understanding the complexities of progeria. He was curious, consistently seeking new perspectives, both within and outside of mainstream science. His engagement in gene therapy for HGPS spanned from the preparation of his graduation thesis at Oviedo University in Spain until his passing. As a member of the Progeria Research Foundation, he collaborated closely with researchers trying to obtain FDA approval for the first gene therapy for progeria. A few years a","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811515","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":"Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics","authors":"Iman M. Al-Naggar,&nbsp;Maria Antony,&nbsp;Dylan Baker,&nbsp;Lichao Wang,&nbsp;Lucas Da Cunha Godoy,&nbsp;Chia-Ling Kuo,&nbsp;Matthew O. Fraser,&nbsp;Phillip P. Smith,&nbsp;Ming Xu,&nbsp;George A. Kuchel","doi":"10.1111/acel.14399","DOIUrl":"10.1111/acel.14399","url":null,"abstract":"<p>Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging-related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy-induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high-fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD-induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine-blood barrier.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790522","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":"Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity","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.14386","DOIUrl":"10.1111/acel.14386","url":null,"abstract":"<p>Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals. Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle-aged: 99 ± 27 pmol O₂.s⁻¹.mg⁻¹, <i>p</i> = 0.95) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle-aged: 5.68 ± 1.48%, <i>p</i> = 0.25), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle-aged: 1.55 ± 0.15 A.U., <i>p</i> &lt; 0.0001), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle-aged: 13.55 ± 4.10%, <i>p</i> = 0.002) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle-aged: 13.92 ± 4.95%, <i>p</i> = 0.005). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density. Collectively, our work highlights the critical role of skeletal muscle mitochondria in age-associated declines in physical function.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765053","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":"Restoration of hair follicle inductive properties by depletion of senescent cells","authors":"Alberto Pappalardo,&nbsp;Jin Yong Kim,&nbsp;Hasan Erbil Abaci,&nbsp;Angela M. Christiano","doi":"10.1111/acel.14353","DOIUrl":"10.1111/acel.14353","url":null,"abstract":"<p>Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded <i>in vitro</i>, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP-mediated repressive interactions in human DP culture, resulting in an increased Wnt-active cell population. In hair reconstitution assays, senolytic-depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic-depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell-based therapies.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754367","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":"Overlooked histories in ageing research: Pioneering women at the foundation of our field","authors":"Marina Ezcurra,&nbsp;Colin Selman,&nbsp;Jennifer Tullet,&nbsp;Nathan Woodling","doi":"10.1111/acel.14432","DOIUrl":"10.1111/acel.14432","url":null,"abstract":"<p>A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer ‘history of the field’ that many of us present in our classrooms, conference halls and writings often tends to be dominated by men. Although numerous men have made fundamental observations that have shaped our understanding of ageing from both a mechanistic and evolutionary perspective, the unfortunate reality is that women making similar contributions have not received equal recognition throughout much of our field's history. As a starting point for wider representation and further conversations in this area, we present here a short list of women—Marjory Warren, Lillian Jane Martin, Margaret Alexander Ohlson, Rebeca Gerschman and Marion J. Lamb—whose contributions were foundational to ageing research in the 20th century. Their work spanned theoretical, experimental and clinical insight into the biology of ageing—and yet their names are too seldom mentioned when introducing our field. We hope this list can be a starting point for a more inclusive recognition of the diverse scientists who helped pave the way for our field today.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737961","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":"Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats","authors":"Zixuan Wang,&nbsp;Chenyi Yang,&nbsp;Xinyi Wang,&nbsp;Huihui Liao,&nbsp;Xing Liu,&nbsp;Huan Liu,&nbsp;Miao Zhang,&nbsp;Lin Zhang,&nbsp;Haiyun Wang","doi":"10.1111/acel.14418","DOIUrl":"10.1111/acel.14418","url":null,"abstract":"<p>Perioperative neurocognitive disorders (PND) is common in aged mild cognitive impairment (MCI) patients and can accelerate the progression to dementia. This process involves heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1)-mediated aggregates of stress granules (SGs), while RUVBL2 influences the dynamics of these SGs. Our research explored a new target for modulating hnRNAPA2/B1-SGs dynamics to accelerate their disassembly and potentially delay MCI progression due to PND. We assessed the effect of hippocampal RUVBL2 knockdown on hnRNPA2/B1-SGs in aged MCI rats through behavioral studies, biochemical experiments and MRI. We also examined hnRNPA2/B1-SGs dynamics using immunofluorescence staining and fluorescence recovery after photobleaching (FRAP) in rat primary hippocampal neurons. Our results revealed that hnRNPA2/B1 in the hippocampus of aged MCI rats translocates to the cytoplasm to form SGs following anesthesia. RUVBL2 knockdown promotes the disappearance of hnRNPA2/B1-SGs, allowing hnRNPA2/B1 to return to the nucleus and enhancing functional activity in the brain regions of aged MCI rats. In primary hippocampal neurons, RUVBL2 deletion facilitated hnRNPA2/B1-SGs transition from hydrogel to liquid, promoting disassembly. We compared three commonly used general anesthetics—3% sevoflurane, 40 mg·kg⁻¹·h⁻¹ propofol, and 9% desflurane. Sevoflurane upregulated RUVBL2, which decreased the intraneuronal pH and disrupted energy metabolism. These changes resulted in greater stabilization of hnRNPA2/B1- SGs. In conclusion, our findings indicated that the knockdown of RUVBL2 expression contributes to the transition of hnRNPA2/B1-SGs from the hydrogel phase to the liquid phase. Targeted interference with RUVBL2 may represent a novel approach to delay the progression to dementia due to PND in aged MCI patients.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749388","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}