Aging Cell最新文献_第2页

Piwi mutant germ cells transmit a form of heritable stress that promotes longevity. Piwi 突变生殖细胞会传递一种可遗传的压力，从而促进长寿。

IF 8 1区医学

Aging Cell Pub Date : 2024-11-09 DOI: 10.1111/acel.14350

Bree Heestand, Ben McCarthy, Matt Simon, Evan H Lister-Shimauchi, Stephen Frenk, Shawn Ahmed

{"title":"Piwi mutant germ cells transmit a form of heritable stress that promotes longevity.","authors":"Bree Heestand, Ben McCarthy, Matt Simon, Evan H Lister-Shimauchi, Stephen Frenk, Shawn Ahmed","doi":"10.1111/acel.14350","DOIUrl":"https://doi.org/10.1111/acel.14350","url":null,"abstract":"The C. elegans Argonaute protein PRG-1/Piwi and associated piRNAs protect metazoan genomes by silencing transposons and other types of foreign DNA. As prg-1 mutants are propagated, their fertility deteriorates prior to the onset of a reproductive arrest phenotype that resembles a starvation-induced stress response. We found that late-generation prg-1 mutants with substantially reduced fertility were long-lived, whereas early- or mid-generation prg-1 mutants had normal lifespans. Loss of the stress response transcription factor DAF-16 caused mid- or late-generation prg-1 mutants to live very short lives, whereas overexpression of DAF-16 enabled both mid- and late-generation prg-1 mutants to live long. Cytoplasmic P-bodies that respond to stress increased in long-lived late-generation prg-1 mutants and were transmitted to F1 but not F2 cross-progeny. Moreover, moderate levels of heritable stress shorten late-generation prg-1 mutant longevity when DAF-16 or P bodies are deficient. Together, these results suggest that the longevity of late-generation prg-1 mutants is a hormetic stress response. However, dauer larvae that occur in response to stress were not observed in late-generation prg-1 mutants. Small germ cell nucleoli that depended on germline DAF-16 were present in late-generation prg-1 mutants but were not necessary for their longevity. We propose that prg-1 mutant germ cells transmit a form of heritable stress, high levels of which promote longevity and strongly reduce fertility. The heritable stress transmitted by prg-1/Piwi mutant germ cells may be generally relevant to epigenetic inheritance of longevity.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14350"},"PeriodicalIF":8.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612885","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

Locus coeruleus vulnerability to tau hyperphosphorylation in a rat model. 在大鼠模型中，神经节对 tau 过度磷酸化的脆弱性

IF 8 1区医学

Aging Cell Pub Date : 2024-11-09 DOI: 10.1111/acel.14405

Tamunotonye Omoluabi, Zia Hasan, Jessie E Piche, Abeni R S Flynn, Jules J E Doré, Susan G Walling, Andrew C W Weeks, Touati Benoukraf, Qi Yuan

{"title":"Locus coeruleus vulnerability to tau hyperphosphorylation in a rat model.","authors":"Tamunotonye Omoluabi, Zia Hasan, Jessie E Piche, Abeni R S Flynn, Jules J E Doré, Susan G Walling, Andrew C W Weeks, Touati Benoukraf, Qi Yuan","doi":"10.1111/acel.14405","DOIUrl":"https://doi.org/10.1111/acel.14405","url":null,"abstract":"Post-mortem investigations indicate that the locus coeruleus (LC) is the initial site of hyperphosphorylated pretangle tau, a precursor to neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD). The presence of pretangle tau and NFTs correlates with AD progression and symptomatology. LC neuron integrity and quantity are linked to cognitive performance, with degeneration strongly associated with AD. Despite their importance, the mechanisms of pretangle tau-induced LC degeneration are unclear. This study examined the transcriptomic and mitochondrial profiles of LC noradrenergic neurons after transduction with pseudophosphorylated human tau. Tau hyperphosphorylation increased the somatic expression of the L-type calcium channel (LTCC), impaired mitochondrial health, and led to deficits in spatial and olfactory learning. Sex-dependent alterations in gene expression were observed in rats transduced with pretangle tau. Chronic LTCC blockade prevented behavioral deficits and altered mitochondrial mRNA expression, suggesting a potential link between LTCC hyperactivity and mitochondrial dysfunction. Our research provides insights into the consequences of tau pathology in the originating structure of AD.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14405"},"PeriodicalIF":8.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612875","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

Proteo-metabolomic insights for early dual physical and cognitive impairments: A search for biomarkers of healthy aging based on muscle-brain crosstalk. 蛋白质代谢组学对早期身体和认知双重损伤的启示：基于肌肉-大脑串联寻找健康老化的生物标志物。

IF 8 1区医学

Aging Cell Pub Date : 2024-11-08 DOI: 10.1111/acel.14407

Yi-Long Huang, Wei-Ju Chang, Chen-Hua Huang, Chao-Hsiung Lin, Li-Ning Peng, Chih-Ping Chung, Liang-Kung Chen, Wei-Ju Lee

{"title":"Proteo-metabolomic insights for early dual physical and cognitive impairments: A search for biomarkers of healthy aging based on muscle-brain crosstalk.","authors":"Yi-Long Huang, Wei-Ju Chang, Chen-Hua Huang, Chao-Hsiung Lin, Li-Ning Peng, Chih-Ping Chung, Liang-Kung Chen, Wei-Ju Lee","doi":"10.1111/acel.14407","DOIUrl":"https://doi.org/10.1111/acel.14407","url":null,"abstract":"We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle-brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle-brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14407"},"PeriodicalIF":8.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612892","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

Featured Cover 特色封面

IF 7.8 1区医学

Aging Cell Pub Date : 2023-10-16 DOI: 10.1111/acel.14016

Hasan Ishtayeh, Margarita Galves, Tania T. Barnatan, Yevgeny Berdichevsky, Fatima Amer-Sarsour, Metsada Pasmanik-Chor, Itzhak Braverman, Sergiu C. Blumen, Avraham Ashkenazi

引用次数: 0

Intersection clock reveals a rejuvenation event during human embryogenesis 交叉点时钟揭示了人类胚胎发生过程中的再生事件。

IF 7.8 1区医学

Aging Cell Pub Date : 2023-10-02 DOI: 10.1111/acel.13922

Csaba Kerepesi, Vadim N. Gladyshev

{"title":"Intersection clock reveals a rejuvenation event during human embryogenesis","authors":"Csaba Kerepesi, Vadim N. Gladyshev","doi":"10.1111/acel.13922","DOIUrl":"10.1111/acel.13922","url":null,"abstract":"Recent research revealed a rejuvenation event during early development of mice. Here, by examining epigenetic age dynamics of human embryogenesis, we tested whether a similar event exists in humans. For this purpose, we developed an epigenetic clock method, the intersection clock, that utilizes bisulfite sequencing in a way that maximizes the use of informative CpG sites with no missing clock CpG sites in test samples and applied it to human embryo development data. We observed no changes in the predicted epigenetic age between cleavage stage and blastocyst stage embryos; however, a significant decrease was observed between blastocysts and cells representing the epiblast. Additionally, by applying the intersection clock to datasets spanning pre and postimplantation, we found no significant change in the epigenetic age during preimplantation stages; however, the epigenetic age of postimplantation samples was lower compared to the preimplantation stages. We further investigated the epigenetic age of primed (representing early postimplantation) and naïve (representing preimplantation) pluripotent stem cells and observed that in all cases the epigenetic age of primed cells was significantly lower than that of naïve cells. Together, our data suggest that human embryos are rejuvenated during early embryogenesis. Hence, the rejuvenation event is conserved between the mouse and human, and it occurs around the gastrulation stage in both species. Beyond this advance, the intersection clock opens the way for other epigenetic age studies based on human bisulfite sequencing datasets as opposed to methylation arrays.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093534","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: 1

Transcriptional changes of the aging lung 衰老肺的转录变化。

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-14 DOI: 10.1111/acel.13969

Minxue Jia, Paula A. Agudelo Garcia, Jose A. Ovando-Ricardez, Tracy Tabib, Humberto T. Bittar, Robert A. Lafyatis, Ana L. Mora, Panayiotis V. Benos, Mauricio Rojas

{"title":"Transcriptional changes of the aging lung","authors":"Minxue Jia, Paula A. Agudelo Garcia, Jose A. Ovando-Ricardez, Tracy Tabib, Humberto T. Bittar, Robert A. Lafyatis, Ana L. Mora, Panayiotis V. Benos, Mauricio Rojas","doi":"10.1111/acel.13969","DOIUrl":"10.1111/acel.13969","url":null,"abstract":"Aging is a natural process associated with declined organ function and higher susceptibility to developing chronic diseases. A systemic single-cell type-based study provides a unique opportunity to understand the mechanisms behind age-related pathologies. Here, we use single-cell gene expression analysis comparing healthy young and aged human lungs from nonsmoker donors to investigate age-related transcriptional changes. Our data suggest that aging has a heterogenous effect on lung cells, as some populations are more transcriptionally dynamic while others remain stable in aged individuals. We found that monocytes and alveolar macrophages were the most transcriptionally affected populations. These changes were related to inflammation and regulation of the immune response. Additionally, we calculated the LungAge score, which reveals the diversity of lung cell types during aging. Changes in DNA damage repair, fatty acid metabolism, and inflammation are essential for age prediction. Finally, we quantified the senescence score in aged lungs and found that the more biased cells toward senescence are immune and progenitor cells. Our study provides a comprehensive and systemic analysis of the molecular signatures of lung aging. Our LungAge signature can be used to predict molecular signatures of physiological aging and to detect common signatures of age-related lung diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598259","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: 1

Erratum to: The variant senescence-associated secretory phenotype induced by centrosome amplification constitutes a pathway that activates hypoxia-inducible factor-1α 勘误表：中心体扩增诱导的变异衰老相关分泌表型构成了激活缺氧诱导因子-1α的途径

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-11 DOI: 10.1111/acel.13991

引用次数: 0

Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome progeroid-Cokayne综合征加速衰老的表观基因组特征

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-08 DOI: 10.1111/acel.13959

Clément Crochemore, Claudia Chica, Paolo Garagnani, Giovanna Lattanzi, Steve Horvath, Alain Sarasin, Claudio Franceschi, Maria Giulia Bacalini, Miria Ricchetti

{"title":"Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome","authors":"Clément Crochemore, Claudia Chica, Paolo Garagnani, Giovanna Lattanzi, Steve Horvath, Alain Sarasin, Claudio Franceschi, Maria Giulia Bacalini, Miria Ricchetti","doi":"10.1111/acel.13959","DOIUrl":"10.1111/acel.13959","url":null,"abstract":"Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome-wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS-specific epigenomic signature (progeroid-related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. A large fraction of CS-specific DNAm changes were associated with expression changes in CS samples, including in previously reported post-mortem cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of Alu sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid/degenerative phenotype.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13959","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178842","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

Intact mitochondrial function in the setting of telomere-induced senescence 端粒诱导衰老过程中线粒体的完整功能。

IF 7.8 1区医学

Aging Cell Pub Date : 2023-09-08 DOI: 10.1111/acel.13941

Daniel I. Sullivan, Fiona M. Bello, Agustin Gil Silva, Kevin M. Redding, Luca Giordano, Angela M. Hinchie, Kelly E. Loughridge, Ana L. Mora, Melanie Königshoff, Brett A. Kaufman, Michael J. Jurczak, Jonathan K. Alder

{"title":"Intact mitochondrial function in the setting of telomere-induced senescence","authors":"Daniel I. Sullivan, Fiona M. Bello, Agustin Gil Silva, Kevin M. Redding, Luca Giordano, Angela M. Hinchie, Kelly E. Loughridge, Ana L. Mora, Melanie Königshoff, Brett A. Kaufman, Michael J. Jurczak, Jonathan K. Alder","doi":"10.1111/acel.13941","DOIUrl":"10.1111/acel.13941","url":null,"abstract":"Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere-binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence, which may facilitate continued cellular functions.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187590","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

Deciphering RNA m6A regulation in aging: Perspectives on current advances and future directions 解读衰老中的RNA m6A调控：当前进展和未来方向展望

IF 7.8 1区医学

Aging Cell Pub Date : 2023-08-28 DOI: 10.1111/acel.13972

Zeming Wu, Jie Ren, Guang-Hui Liu

{"title":"Deciphering RNA m6A regulation in aging: Perspectives on current advances and future directions","authors":"Zeming Wu, Jie Ren, Guang-Hui Liu","doi":"10.1111/acel.13972","DOIUrl":"https://doi.org/10.1111/acel.13972","url":null,"abstract":"N6-methyladenosine (m6A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m6A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m6A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m6A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"22 10","pages":""},"PeriodicalIF":7.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.13972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230096","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