Aging Cell最新文献_第10页

A defective splicing machinery promotes senescence through MDM4 alternative splicing. 剪接机制缺陷通过 MDM4 替代剪接促进衰老。

IF 8 1区医学

Aging Cell Pub Date : 2024-08-08 DOI: 10.1111/acel.14301

Mathieu Deschênes, Mathieu Durand, Marc-Alexandre Olivier, Alicia Pellerin-Viger, Francis Rodier, Benoit Chabot

引用次数: 0

The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice. cGAS-STING 通路的激活会导致老年小鼠子宫接受能力异常。

IF 8 1区医学

Aging Cell Pub Date : 2024-08-07 DOI: 10.1111/acel.14303

Si-Ting Chen, Wen-Wen Shi, Feng Ran, Cheng-Kan Liu, Hui-Na Luo, Li-Juan Wu, Ying Wu, Tong-Tong Zhang, Zeng-Ming Yang

{"title":"The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.","authors":"Si-Ting Chen, Wen-Wen Shi, Feng Ran, Cheng-Kan Liu, Hui-Na Luo, Li-Juan Wu, Ying Wu, Tong-Tong Zhang, Zeng-Ming Yang","doi":"10.1111/acel.14303","DOIUrl":"https://doi.org/10.1111/acel.14303","url":null,"abstract":"Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence. 短期饥饿可激活 AMPK 并恢复线粒体无机多磷酸，但无法逆转相关的神经元衰老。

IF 8 1区医学

Aging Cell Pub Date : 2024-08-05 DOI: 10.1111/acel.14289

Luca Tagliafico, Renata T Da Costa, Lavinia Boccia, Sheida Kavehmoghaddam, Bryan Ramirez, Malgorzata Tokarska-Schlattner, Ernest R Scoma, Vedangi Hambardikar, Tommaso Bonfiglio, Irene Caffa, Fiammetta Monacelli, Uwe Schlattner, J Nicholas Betley, Alessio Nencioni, Maria E Solesio

{"title":"Short-term starvation activates AMPK and restores mitochondrial inorganic polyphosphate, but fails to reverse associated neuronal senescence.","authors":"Luca Tagliafico, Renata T Da Costa, Lavinia Boccia, Sheida Kavehmoghaddam, Bryan Ramirez, Malgorzata Tokarska-Schlattner, Ernest R Scoma, Vedangi Hambardikar, Tommaso Bonfiglio, Irene Caffa, Fiammetta Monacelli, Uwe Schlattner, J Nicholas Betley, Alessio Nencioni, Maria E Solesio","doi":"10.1111/acel.14289","DOIUrl":"10.1111/acel.14289","url":null,"abstract":"Neuronal senescence is a major risk factor for the development of many neurodegenerative disorders. The mechanisms that drive neurons to senescence remain largely elusive; however, dysregulated mitochondrial physiology seems to play a pivotal role in this process. Consequently, strategies aimed to preserve mitochondrial function may hold promise in mitigating neuronal senescence. For example, dietary restriction has shown to reduce senescence, via a mechanism that still remains far from being totally understood, but that could be at least partially mediated by mitochondria. Here, we address the role of mitochondrial inorganic polyphosphate (polyP) in the intersection between neuronal senescence and dietary restriction. PolyP is highly present in mammalian mitochondria; and its regulatory role in mammalian bioenergetics has already been described by us and others. Our data demonstrate that depletion of mitochondrial polyP exacerbates neuronal senescence, independently of whether dietary restriction is present. However, dietary restriction in polyP-depleted cells activates AMPK, and it restores some components of mitochondrial physiology, even if this is not sufficient to revert increased senescence. The effects of dietary restriction on polyP levels and AMPK activation are conserved in differentiated SH-SY5Y cells and brain tissue of male mice. Our results identify polyP as an important component in mitochondrial physiology at the intersection of dietary restriction and senescence, and they highlight the importance of the organelle in this intersection.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Senescence detection using reflected light. 利用反射光进行衰老检测

IF 8 1区医学

Aging Cell Pub Date : 2024-08-05 DOI: 10.1111/acel.14295

Benjamin Dedic, Leo Westerberg, Andrea Mosqueda Solís, Kyle D Dumont, Jorge L Ruas, Anders Thorell, Erik Näslund, Kirsty L Spalding

{"title":"Senescence detection using reflected light.","authors":"Benjamin Dedic, Leo Westerberg, Andrea Mosqueda Solís, Kyle D Dumont, Jorge L Ruas, Anders Thorell, Erik Näslund, Kirsty L Spalding","doi":"10.1111/acel.14295","DOIUrl":"https://doi.org/10.1111/acel.14295","url":null,"abstract":"Senescence is an important cellular program occurring in development, tissue repair, cancer, and aging. Increased senescence is also associated with disease states, including obesity and Type 2 diabetes (T2D). Characterizing and quantifying senescent cells at a single cell level has been challenging and particularly difficult in large primary cells, such as human adipocytes. In this study, we present a novel approach that utilizes reflected light for accurate senescence-associated beta-galactosidase (SABG) staining measurements, which can be integrated with immunofluorescence and is compatible with primary mature adipocytes from both human and mouse, as well as with differentiated 3T3-L1 cells. This technique provides a more comprehensive classification of a cell's senescent state by incorporating multiple criteria, including robust sample-specific pH controls. By leveraging the precision of confocal microscopy to detect X-gal crystals using reflected light, we achieved superior sensitivity over traditional brightfield techniques. This strategy allows for the capture of all X-gal precipitates in SABG-stained samples, revealing diverse X-gal staining patterns and improved detection sensitivity. Additionally, we demonstrate that reflected light outperforms western blot analysis for the detection and quantification of senescence in mature human adipocytes, as it offers a more accurate representation of SABG activity. This detection strategy enables a more thorough investigation of senescent cell characteristics and specifically a deeper look at the relationship between adipocyte senescence and obesity associated disorders, such as T2D.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-specific growth and lifespan effects of germline removal in the dioecious nematode Caenorhabditis remanei. 雌雄异体线虫Caenorhabditis remanei种系去除对其生长和寿命的性别特异性影响

IF 8 1区医学

Aging Cell Pub Date : 2024-07-31 DOI: 10.1111/acel.14290

Martin I Lind, Brian S Mautz, Hanne Carlsson, Andrea Hinas, Erik Gudmunds, Alexei A Maklakov

{"title":"Sex-specific growth and lifespan effects of germline removal in the dioecious nematode Caenorhabditis remanei.","authors":"Martin I Lind, Brian S Mautz, Hanne Carlsson, Andrea Hinas, Erik Gudmunds, Alexei A Maklakov","doi":"10.1111/acel.14290","DOIUrl":"https://doi.org/10.1111/acel.14290","url":null,"abstract":"Germline regulates the expression of life-history traits and mediates the trade-off between reproduction and somatic maintenance. However, germline maintenance in itself can be costly, and the costs can vary between the sexes depending on the number of gametes produced across the lifetime. We tested this directly by germline ablation using glp-1 RNA interference (RNAi) in a dioecious nematode Caenorhabditis remanei. Germline removal strongly increased heat-shock resistance in both sexes, thus confirming the role of the germline in regulating somatic maintenance. However, germline removal resulted in increased lifespan only in males. High costs of mating strongly reduced lifespan in both sexes and obliterated the survival benefit of germline-less males even though neither sex produced any offspring. Furthermore, germline removal reduced male growth before maturation but not in adulthood, while female growth rate was reduced both before and especially after maturation. Thus, germline removal improves male lifespan without major growth costs, while germline-less females grow slower and do not live longer than reproductively functional counterparts in the absence of environmental stress. Overall, these results suggest that germline maintenance is costlier for males than for females in C. remanei.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The circadian rhythm: A key variable in aging? 昼夜节律：衰老的关键因素？

IF 8 1区医学

Aging Cell Pub Date : 2024-07-30 DOI: 10.1111/acel.14268

Patrick R Winterhalter, Adrian-Iustin Georgevici, Nitin J Gharpure, Gábor Szabó, Andreas Simm

{"title":"The circadian rhythm: A key variable in aging?","authors":"Patrick R Winterhalter, Adrian-Iustin Georgevici, Nitin J Gharpure, Gábor Szabó, Andreas Simm","doi":"10.1111/acel.14268","DOIUrl":"https://doi.org/10.1111/acel.14268","url":null,"abstract":"The determination of age-related transcriptional changes may contribute to the understanding of health and life expectancy. The broad application of results from age cohorts may have limitations. Altering sample sizes per time point or sex, using a single mouse strain or tissue, a limited number of replicates, or omitting the middle of life can bias the surveys. To achieve higher general validity and to identify less distinctive players, bulk RNA sequencing of a mouse cohort, including seven organs of two strains from both sexes of 5 ages, was performed. Machine learning by bootstrapped variable importance and selection methodology (Boruta) was used to identify common aging features where the circadian rhythms (CiR) transcripts appear as promising age markers in an unsupervised analysis. Pathways of 11 numerically analyzed local network clusters were affected and classified into four major gene expression profiles, whereby CiR and proteostasis candidates were particularly conspicuous with partially opposing changes. In a data-based interaction association network, the CiR-proteostasis axis occupies an exposed central position, highlighting its relevance. The computation of 11,830 individual transcript associations provides potential superordinate contributors, such as hormones, to age-related changes, as in CiR. In hormone-sensitive LNCaP cells, short-term supraphysiologic levels of the sex hormones dihydrotestosterone or estradiol increase the expression of the CiR transcript Bhlhe40 and the associated senescence regulator Cdkn2b (p15). According to these findings, the bilateral dysregulation of CiR appears as a fundamental protagonist of aging, whose transcripts could serve as a biological marker and its restoration as a therapeutic opportunity.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histone β-hydroxybutyrylation is critical in reversal of sarcopenia. 组蛋白β-羟基丁酰化在逆转肌肉疏松症中至关重要。

IF 8 1区医学

Aging Cell Pub Date : 2024-07-30 DOI: 10.1111/acel.14284

Qiquan Wang, Xinqiang Lan, Hao Ke, Siman Xu, Chunping Huang, Jiali Wang, Xiang Wang, Tiane Huang, Xia Wu, Mengxin Chen, Yingqi Guo, Lin Zeng, Xiao-Li Tian, Yang Xiang

{"title":"Histone β-hydroxybutyrylation is critical in reversal of sarcopenia.","authors":"Qiquan Wang, Xinqiang Lan, Hao Ke, Siman Xu, Chunping Huang, Jiali Wang, Xiang Wang, Tiane Huang, Xia Wu, Mengxin Chen, Yingqi Guo, Lin Zeng, Xiao-Li Tian, Yang Xiang","doi":"10.1111/acel.14284","DOIUrl":"https://doi.org/10.1111/acel.14284","url":null,"abstract":"Sarcopenia, a leading cause for global disability and mortality, is an age-related muscular disorder, characterized by accelerated muscle mass loss and functional decline. It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating β-hydroxybutyrate (β-HB) levels. Whether the elevated β-HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans and mouse models that an increase of β-HB reverse myofiber atrophy and improves motor functions at advanced ages. β-HB-induced histone lysine β-hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that β-HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects. 认识的不确定性对预测返老还童效果的老化时钟可靠性提出了挑战。

IF 8 1区医学

Aging Cell Pub Date : 2024-07-28 DOI: 10.1111/acel.14283

Dmitrii Kriukov, Ekaterina Kuzmina, Evgeniy Efimov, Dmitry V Dylov, Ekaterina E Khrameeva

{"title":"Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.","authors":"Dmitrii Kriukov, Ekaterina Kuzmina, Evgeniy Efimov, Dmitry V Dylov, Ekaterina E Khrameeva","doi":"10.1111/acel.14283","DOIUrl":"https://doi.org/10.1111/acel.14283","url":null,"abstract":"Epigenetic aging clocks have been widely used to validate rejuvenation effects during cellular reprogramming. However, these predictions are unverifiable because the true biological age of reprogrammed cells remains unknown. We present an analytical framework to consider rejuvenation predictions from the uncertainty perspective. Our analysis reveals that the DNA methylation profiles across reprogramming are poorly represented in the aging data used to train clock models, thus introducing high epistemic uncertainty in age estimations. Moreover, predictions of different published clocks are inconsistent, with some even suggesting zero or negative rejuvenation. While not questioning the possibility of age reversal, we show that the high clock uncertainty challenges the reliability of rejuvenation effects observed during in vitro reprogramming before pluripotency and throughout embryogenesis. Conversely, our method reveals a significant age increase after in vivo reprogramming. We recommend including uncertainty estimation in future aging clock models to avoid the risk of misinterpreting the results of biological age prediction.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cysteine protease cathepsin B promotes lysosome integrity to extend the lifespan of alternative day fasting worms. 半胱氨酸蛋白酶 cathepsin B 可促进溶酶体的完整性，从而延长隔日禁食蠕虫的寿命。

IF 8 1区医学

Aging Cell Pub Date : 2024-07-24 DOI: 10.1111/acel.14286

Xue Yin, Fangzhou Dai, Dongyang Ran, Yutong Zhang, Zhi Qu, Shanqing Zheng

{"title":"Cysteine protease cathepsin B promotes lysosome integrity to extend the lifespan of alternative day fasting worms.","authors":"Xue Yin, Fangzhou Dai, Dongyang Ran, Yutong Zhang, Zhi Qu, Shanqing Zheng","doi":"10.1111/acel.14286","DOIUrl":"https://doi.org/10.1111/acel.14286","url":null,"abstract":"Alternative day fasting (ADF) has been shown to enhance the lifespan of animals. However, human trials evaluating the efficacy of ADF have only recently emerged, presenting challenges due to the extreme nature of this dietary regimen. To better understand the effects of ADF, we investigated its impact using Caenorhabditis elegans as a model organism. Our findings reveal that ADF extends the lifespan of worms nourished on animal-based protein source, while those fed with plant-based protein as the primary protein source do not experience such benefits. Remarkably, initiating ADF during midlife is sufficient to prolong lifespan, whereas implementation during youth results in developmental damage, and in older age, fails to provide additional extension effects. Furthermore, we discovered that midlife ADF up-regulates the expression of two cysteine protease cathepsin B genes, cpr-2 and cpr-5, which preserve lysosomal integrity and enhance its function in digesting aggregated proteins, as well as enhancing lipid metabolism and ameliorating neurodegenerative disease markers and phenomena during aging. This suggests that midlife ADF has long lasting anti-aging effects and may delay the onset of related diseases, specifically in animals consuming animal-based protein source. These findings offer valuable insights into the effects of ADF and provide guidance for future research and potential applications in individuals.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis. DNA 叉重塑蛋白 Zranb3 和 Smarcal1 是衰老造血过程中不可或缺的独特蛋白。

IF 8 1区医学

Aging Cell Pub Date : 2024-07-23 DOI: 10.1111/acel.14281

Saul Kushinsky, Matthew V Puccetti, Clare M Adams, Irina Shkundina, Nikkole James, Brittany M Mahon, Peter Michener, Christine M Eischen

{"title":"DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.","authors":"Saul Kushinsky, Matthew V Puccetti, Clare M Adams, Irina Shkundina, Nikkole James, Brittany M Mahon, Peter Michener, Christine M Eischen","doi":"10.1111/acel.14281","DOIUrl":"10.1111/acel.14281","url":null,"abstract":"Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and Smarcal1, have surprisingly specialized roles in distinct HSPC populations. While both proteins actively mitigate replication stress and prevent DNA damage and breaks during lifelong hematopoiesis, the loss of either resulted in distinct biochemical and biological consequences. Notably, defective long-term HSC function, revealed with bone marrow transplantation, caused hematopoiesis abnormalities in young mice lacking Zranb3. Aging significantly worsened these hematopoiesis defects in Zranb3-deficient mice, including accelerating the onset of myeloid-biased hematopoietic dysregulation to early in life. Such Zranb3-deficient HSPC abnormalities with age were driven by accumulated DNA damage and replication stress. Conversely, Smarcal1 loss primarily negatively affected progenitor cell functions that were exacerbated with aging, resulting in a lymphoid bias. Simultaneous loss of both Zranb3 and Smarcal1 compounded HSPC defects. Additionally, HSPC DNA replication fork dynamics had unanticipated HSPC type and age plasticity that depended on the stress and Zranb3 and/or Smarcal1. Our data reveal both Zranb3 and Smarcal1 have essential HSPC cell intrinsic functions in lifelong hematopoiesis that protect HSPCs from replication stress and DNA damage in unexpected, unique ways.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0