Aging Cell最新文献

{"title":"Additional Cover","authors":"Sachin Kumar,&nbsp;Jeffrey D. Vassallo,&nbsp;Kalpana J. Nattamai,&nbsp;Aishlin Hassan,&nbsp;Angelika Vollmer,&nbsp;Rebekah Karns,&nbsp;Mehmet Sacma,&nbsp;Travis Nemkov,&nbsp;Angelo D'Alessandro,&nbsp;Hartmut Geiger","doi":"10.1111/acel.14380","DOIUrl":"https://doi.org/10.1111/acel.14380","url":null,"abstract":"<p>Cover legend: The cover image is based on the Article <i>Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment</i> by Sachin Kumar et al.,\u0000https://doi.org/10.1111/acel.14324\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 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429797","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":"CaMKIIα-TARPγ8 signaling mediates hippocampal synaptic impairment in aging","authors":"Zhao JianHua,&nbsp;MingCan Li,&nbsp;Qilin Hu,&nbsp;Peter Donoghue,&nbsp;Sanwei Jiang,&nbsp;Junmei Li,&nbsp;Songji Li,&nbsp;Xinyi Ren,&nbsp;Ziyuan Zhang,&nbsp;Jingzhi Du,&nbsp;Yi Yu,&nbsp;Paul Chazot,&nbsp;Chengbiao Lu","doi":"10.1111/acel.14349","DOIUrl":"10.1111/acel.14349","url":null,"abstract":"<p>Aging-related decline in memory and synaptic function are associated with the dysregulation of calcium homeostasis, attributed to the overexpression of voltage-gated calcium channels (VGCC). The membrane insertion of AMPAR governed by the AMPAR auxiliary proteins is essential for synaptic transmission and plasticity (LTP). In this study, we demonstrated the hippocampal expression of the transmembrane AMPAR regulatory proteins γ-8 (TARPγ8) was reduced in aged mice along with the reduced CaMKIIα activity and memory impairment. We further showed that TARPγ8 expression was dependent on CaMKIIα activity. Inhibition of CaMKIIα activity significantly reduced the hippocampal TARPγ8 expression and CA3-CA1 LTP in young mice to a similar level to that of the aged mice. Furthermore, the knockdown of hippocampal TARPγ8 impaired LTP and memory in young mice, which mimicked the aging-related changes. We confirmed the enhanced hippocampal VGCC (Cav-1.3) expression in aged mice and found that inhibition of VGCC activity largely increased both p-CaMKIIα and TARPγ8 expression in aged mice, whereas inhibition of NMDAR or Calpains had no effect. In addition, we found that the exogenous expression of human TARPγ8 in the hippocampus in aged mice restored LTP and memory function. Collectively, these results indicate that the synaptic and cognitive impairment in aging is associated with the downregulation of CaMKIIα-TARPγ8 signaling caused by VGCC activation. Our results suggest that TARPγ8 may be a key molecular biomarker for brain aging and that boosting CaMKIIα-TARPγ8 signaling may be critical for the restoration of synaptic plasticity of aging and aging-related diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386559","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 “An interpretable machine learning-based cerebrospinal fluid proteomics clock for predicting age reveals novel insights into brain aging”","authors":"","doi":"10.1111/acel.14363","DOIUrl":"10.1111/acel.14363","url":null,"abstract":"<p>Melendez, J., Sung, Y.J., Orr, M., Yoo, A., Schindler, S., Cruchaga, C., Bateman, R. <i>Aging Cell</i>, 2024. https://doi.org/10.1111/acel.14230</p><p>In the published version of Melendez et al. (2024), an incorrect version of Table 1 was shown.</p><p>The correct table is shown below.\u0000 </p><p>We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386560","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":"Increased levels of extracellular matrix proteins associated with extracellular vesicles from brains of aged mice","authors":"Azariah K. Kaplelach,&nbsp;Charles F. Murchison,&nbsp;Kyoko Kojima,&nbsp;James A. Mobley,&nbsp;Andrew E. Arrant","doi":"10.1111/acel.14359","DOIUrl":"10.1111/acel.14359","url":null,"abstract":"<p>Extracellular vesicles (EVs) are secreted by all major cell types of the brain, providing a mode of intercellular communication and a pathway for disposal of cellular debris. EVs help maintain healthy brain function, but may also contribute to diseases affecting the brain. EVs might contribute to aging of the brain, as aging-related processes such as inflammation and cellular senescence may alter EV cargo, promoting further inflammation and senescence. However, the effects of aging on brain EVs and the function of EVs in the aging brain remain poorly understood. To address this question, we measured the levels and protein cargo of EVs isolated from the brains of 4-, 12-, and 22-month-old C57BL/6J mice. We detected no changes in EV levels, but observed age-dependent changes in EV proteins. EV fractions from aged (22 month old) brains contained higher levels of extracellular matrix proteins than EV fractions from young (4 month old) brains, with intermediate levels in 12-month-old brains. Specifically, EV fractions from aged mice contained elevated levels of hyaluronan and proteoglycan link proteins 1 and 2 and several chondroitin sulfate proteoglycans (CSPGs). Analysis of extracellular matrix in several brain regions of aged mice revealed increased immunolabeling for the CSPG aggrecan, but reduced labeling with <i>Wisteria floribunda</i> agglutinin, which binds to chondroitin sulfate side chains of CSPGs. These data are consistent with prior studies showing changes to the composition of extracellular matrix in aged brains, and indicate a novel association of EVs with changes in the extracellular matrix of the aging brain.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386562","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":"Hippocampal rejuvenation by a single intracerebral injection of one-carbon metabolites in C57BL6 old wild-type mice","authors":"Alejandro Antón-Fernández,&nbsp;Rocío Peinado Cauchola,&nbsp;Félix Hernández,&nbsp;Jesús Ávila","doi":"10.1111/acel.14365","DOIUrl":"10.1111/acel.14365","url":null,"abstract":"<p>The Izpisua-Belmonte group identified a cocktail of metabolites that promote partial reprogramming in cultured muscle cells. We tested the effect of brain injection of these metabolites in the dentate gyrus of aged wild-type mice. The dentate gyrus is a brain region essential for memory function and is extremely vulnerable to aging. A single injection of the cocktail containing four compounds (putrescine, glycine, methionine and threonine) partially reversed brain aging phenotypes and epigenetic alterations in age-associated genes. Our analysis revealed three levels: chromatin methylation, RNA sequencing, and protein expression. Functional studies complemented the previous ones, showing cognitive improvement. In summary, we report the reversal of various age-associated epigenetic changes, such as the transcription factor Zic4, and several changes related to cellular rejuvenation in the dentate gyrus (DG). These changes include increased expression of the Sox2 protein. Finally, the increases in the survival of newly generated neurons and the levels of the NMDA receptor subunit GluN2B were accompanied by improvements in both short-term and long-term memory performance. Based on these results, we propose the use of these metabolites to explore new strategies for the development of potential treatments for age-related brain diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386561","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":"Senescent cell transplantation into the skin induces age-related peripheral dysfunction and cognitive decline","authors":"Ana Catarina Franco,&nbsp;Helene Martini,&nbsp;Stella Victorelli,&nbsp;Anthony B. Lagnado,&nbsp;Saranya P. Wyles,&nbsp;Jennifer L. Rowsey,&nbsp;Nicholas Pirius,&nbsp;Seung-Hwa Woo,&nbsp;Daniela G. Costa,&nbsp;Selim Chaib,&nbsp;Stefan G. Tullius,&nbsp;Tamar Tchkonia,&nbsp;James L. Kirkland,&nbsp;Sundeep Khosla,&nbsp;Diana Jurk,&nbsp;Claudia Cavadas,&nbsp;João F. Passos","doi":"10.1111/acel.14340","DOIUrl":"10.1111/acel.14340","url":null,"abstract":"<p>Cellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age-associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence-associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386563","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":"Associations of age and sex with characteristics of extracellular vesicles and protein-enriched fractions of blood plasma","authors":"Yiyao Huang,&nbsp;Junjie Feng,&nbsp;Jiannan Xu,&nbsp;Liang Dong,&nbsp;Wanting Su,&nbsp;Bo Li,&nbsp;Kenneth W. Witwer,&nbsp;Lei Zheng","doi":"10.1111/acel.14356","DOIUrl":"10.1111/acel.14356","url":null,"abstract":"<p>Extracellular vesicles (EVs) are nanosized particles that are released by various cell types and play vital roles in intercellular communication. They carry biological molecules reflecting the physiological and pathological states of their source cells and tissues, showing potential as biomarkers. However, the impact of demographic factors like age and sex on the properties of blood plasma EVs remains underexplored. This study aims to fill this gap by evaluating how these factors influence the particle count and proteomic profiles of plasma EV preparations and corresponding protein fractions. Plasma samples from 120 healthy volunteers were collected and pooled into six groups: young males (age: 27.6 ± 4.0), young females (27.4 ± 3.8), middle-aged males (48.8 ± 3.8), middle-aged females (48.9 ± 3.9), old males (69.3 ± 3.9), and old females (69.4 ± 4.3). EV- and protein-enriched fractions were separated by size-exclusion chromatography (SEC). Fractions were characterized for particle number concentration and protein composition to identify characteristics affected by age and biological sex. Plasma EVs and corresponding protein fractions exhibited distinct characteristics, with differential enrichment of markers related to EVs and other blood components, including lipoproteins. Proteomic profiles of both EVs and protein fractions displayed sex- and age-dependent differences. Differentially abundant proteins displayed functions previously identified in the context of aging and sex differences, highlighting their utility as biomarkers. Age and sex significantly affect the characteristics of plasma EVs and proteins, potentially influencing their efficacy and interpretation as biomarkers in clinical applications. This study lays the groundwork for detailed mechanistic research to understand how EVs mediate age- and sex-related effects in health.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379604","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":"Cockayne syndrome B protein is implicated in transcription and associated chromatin dynamics in homeostatic and genotoxic conditions","authors":"Anastasios Liakos,&nbsp;Katerina Z. Ntakou-Zamplara,&nbsp;Nelina Angelova,&nbsp;Dimitris Konstantopoulos,&nbsp;Anna-Chloe Synacheri,&nbsp;Zoi Spyropoulou,&nbsp;Iason A. Tsarmaklis,&nbsp;Despoina Korrou-Karava,&nbsp;Georgios Nikolopoulos,&nbsp;Matthieu D. Lavigne,&nbsp;Maria Fousteri","doi":"10.1111/acel.14341","DOIUrl":"10.1111/acel.14341","url":null,"abstract":"<p>The integrity of the actively transcribed genome against helix-distorting DNA lesions relies on a multilayered cellular response that enhances Transcription-Coupled Nucleotide Excision Repair (TC-NER). When defective, TC-NER is causatively associated with Cockayne-Syndrome (CS), a rare severe human progeroid disorder. Although the presence of unresolved transcription-blocking lesions is considered a driver of the aging process, the molecular features of the transcription-driven response to genotoxic stress in CS-B cells remain largely unknown. Here, an in-depth view of the transcriptional and associated chromatin dynamics that occur in CS-B cells illuminates the role of CSB therein. By employing high-throughput genome-wide approaches, we observed that absence of a functional CSB protein results in a delay in transcription progression, more positioned +1 nucleosomes, and less dynamic chromatin structure, compared to normal cells. We found that early after exposure to UV, CS-B cells released RNA polymerase II (RNAPII) from promoter-proximal pause sites into elongation. However, the magnitude of this response and the progression of RNAPII were reduced compared to normal counterparts. Notably, we detected increased post-UV retainment of unprocessed nascent RNA transcripts and chromatin-associated elongating RNAPII molecules. Contrary to the prevailing models, we found that transcription initiation is operational in CS-B fibroblasts early after UV and that chromatin accessibility showed a marginal increase. Our study provides robust evidence for the role of CSB in shaping the transcription and chromatin landscape both in homeostasis and in response to genotoxic insults, which is independent of its known role in TC-NER, and which may underlie major aspects of the CS phenotype.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379613","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":"Mapping epidermal and dermal cellular senescence in human skin aging","authors":"Grace T. Yu,&nbsp;Clarisse Ganier,&nbsp;David B. Allison,&nbsp;Tamara Tchkonia,&nbsp;Sundeep Khosla,&nbsp;James L. Kirkland,&nbsp;Magnus D. Lynch,&nbsp;Saranya P. Wyles","doi":"10.1111/acel.14358","DOIUrl":"10.1111/acel.14358","url":null,"abstract":"<p>Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging. A skin-specific cellular senescence gene set, termed SenSkin™, was curated and confirmed to be elevated in the context of photoaging, chronological aging, and non-replicating <i>CDKN1A</i>+ (p21) cells. In the epidermis, senescent melanocytes were associated with elevated melanin synthesis, suggesting haphazard pigmentation, while in the dermis, senescent reticular dermal fibroblasts were associated with decreased collagen and elastic fiber synthesis. Spatial analysis revealed the tendency for senescent cells to cluster, particularly in photoaged skin. This work proposes a strategy for characterizing age-related skin dysfunction through the lens of cellular senescence and suggests a role for senescent epidermal cells (i.e., melanocytes) and senescent dermal cells (i.e., reticular dermal fibroblasts) in age-related skin sequelae.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379614","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":"Association between prescription drugs and all-cause mortality risk in the UK population","authors":"Jonas Morin,&nbsp;Yves Rolland,&nbsp;Heike A. Bischoff-Ferrari,&nbsp;Alejandro Ocampo,&nbsp;Kevin Perez","doi":"10.1111/acel.14334","DOIUrl":"10.1111/acel.14334","url":null,"abstract":"<p>Although most drugs currently approved are meant to treat specific diseases or symptoms, it has been hypothesized that some might bear a beneficial effect on lifespan in healthy older individuals, outside of their specific disease indication. Such drugs include, among others, metformin, SGLT2 inhibitors and rapamycin. Since 2006, the UK biobank has recorded prescription medication and mortality data for over 500′000 participants, aged between 40 and 70 years old. In this work, we examined the impact of the top 406 prescribed medications on overall mortality rates within the general population of the UK. As expected, most drugs were linked to a shorter lifespan, likely due to the life-limiting nature of the diseases they are prescribed to treat. Importantly, a few drugs were associated with increased lifespans, including notably Sildenafil, Atorvastatin, Naproxen and Estradiol. These retrospective results warrant further investigation in randomized controlled trials.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370331","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}