Aging-Us最新文献

{"title":"rDNA copy number variation and methylation from birth to sexual maturity.","authors":"Alina Michler, Sarah Kießling, Jana Durackova, Ramya Potabattula, Asuman Koparir, Thomas Haaf","doi":"10.18632/aging.206271","DOIUrl":"https://doi.org/10.18632/aging.206271","url":null,"abstract":"<p><p>Ribosomal DNA transcription is essential for ribosome biogenesis and the production of proteins. Using a combination of droplet digital PCR and deep bisulfite sequencing, we have quantified both the absolute number as well as the methylation level of individual rDNA transcription units (TU) in blood samples of 139 young healthy individuals and 141 sex- and age-matched individuals with unsolved syndromal developmental delay (DD), ranging from 0.02 to 18.4 years in age. There were no between-group differences in average promoter methylation, absolute copy number (CN), extreme CN, and hypomethylated (0-10%) presumably active CN. This largely excludes rDNA CN as a modulating factor in DD. The absolute CN in all 280 samples was 423.7 ± 108.4 (median 410, range 153 to 1,000) and the active CN was 175.0 ± 36.4 (median 174, range 70 to 376). Similar to adults, the absolute CN did not change from birth to sexual maturity but was strongly (Pearson <i>ρ</i> = 0.64, <i>P</i> < 0.001) correlated with promoter methylation. In contrast to adults, there was no significant correlation between age and promoter methylation and no age-related loss of active copies from birth to < 20 years. The number of completely unmethylated copies even significantly (Pearson <i>ρ</i> = 0.15; <i>P</i> = 0.01) increased during childhood and adolescence. Our results suggest that rDNA promoter methylation and the age-related loss of active rDNA TU, which are a hallmark of the aging process, start only after reaching sexual maturity.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA).","authors":"Eric T Klopack, Gokul Seshadri, Thalida Em Arpawong, Steve Cole, Bharat Thyagarajan, Eileen M Crimmins","doi":"10.18632/aging.206272","DOIUrl":"https://doi.org/10.18632/aging.206272","url":null,"abstract":"<p><p>Increasingly, research suggests that aging is a coordinated multi-system decline in functioning that occurs at multiple biological levels. We developed and validated a transcriptomic (RNA-based) aging measure we call Transcriptomic Mortality-risk Age (TraMA) using RNA-seq data from the 2016 Health and Retirement Study using elastic net Cox regression analyses to predict 4-year mortality hazard. In a holdout test sample, TraMA was associated with earlier mortality, more chronic conditions, poorer cognitive functioning, and more limitations in activities of daily living. TraMA was also externally validated in the Long Life Family Study and several publicly available datasets. Results suggest that TraMA is a robust, portable RNAseq-based aging measure that is comparable, but independent from past biological aging measures (e.g., GrimAge). TraMA is likely to be of particular value to researchers interested in understanding the biological processes underlying health and aging, and for social, psychological, epidemiological, and demographic studies of health and aging.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic and reversible transcriptomic age shifts induced by COVID-19 in Korean whole blood.","authors":"Kyungwhan An, Yoonsung Kwon, Jihun Bhak, Hyojung Ryu, Sungwon Jeon, Dougu Nam, Jong Bhak","doi":"10.18632/aging.206270","DOIUrl":"https://doi.org/10.18632/aging.206270","url":null,"abstract":"<p><p>We developed the first genome-wide transcriptomic clock specific to Korean ethnicity to predict chronological age using whole blood samples from 440 healthy individuals. Our analysis revealed profound age acceleration - up to 21.31 years - during homeostatic disruption in COVID-19 patients, which reverted to baseline upon recovery. These findings highlight the ability of the blood transcriptome to dynamically track reversible changes in age-associated inflammatory responses during infections. Our study underscores the potential of anti-aging interventions in managing infectious diseases.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a quantitative estimate of muscle age acceleration by a novel phenotypic clock: cross-sectional study in healthy, middle-aged and older adults.","authors":"Lucia Ventura, Antonella Cano, Marco Morrone, Gianluca Martinez, Anna Boi, Maria Grazia Catte, Beniamina Mercante, Nicola Loi, Oksana Yurchyshyn, Giovanni Fiorito, Giuliana Solinas, Sara Cruciani, Donatella Coradduzza, Margherita Maioli, Angelo Zinellu, Ciriaco Carru, Franca Deriu, Andrea Manca","doi":"10.18632/aging.206269","DOIUrl":"10.18632/aging.206269","url":null,"abstract":"<p><p>Sarcopenia is a progressive disease characterized by reductions in muscle mass strength and physical performance. Among the initiatives launched to increase awareness, the European Working Group on Sarcopenia in Older People (EWGSOP) is considered the most influential. This cross-sectional study was planned to develop, in healthy middle-aged and older adults, a novel predictor of sarcopenia based on the motor-functional and anthropometric tests derived from EWGSOP2, which were the primary outcome measures. Participants were tested for body composition, physical performance, blood biomarkers, and risk scores for major healthy issues. Muscle Age Acceleration (MAA) was modelled with Elastic Net regression to extract EWGSOP test mostly contributing to the musculoskeletal ageing trajectory. Two-hundred-fifteen participants were tested (118 women, 97 men; mean age; 66.0±7.3 years). Muscle Age was correlated with chronological age (r = 0.645; <i>p</i> < 0.001). Parsimonious modelling extracted TUG (β = 2.93; 2.48 - to -3.51), ASMM (β = -2.23; -2.99 to -1.67) and Handgrip (β = -1.12; -1.70 to -0.42) for men, and TUG (β = 2.69; 1.96 to 4.19), Handgrip (β = -1.27; -1.56 to -0.98), and Six-MWT (β = -1.15; -1.71 to -0.53) for women. According to MAA, three trajectories were identified: accelerated agers displayed higher risk for sarcopenia (19%), as compared to normal (9%; <i>p</i> < 0.0001) and decelerated (2%; <i>p</i> < 0.0001), paralleled by significant subclinical alterations of haemato-chemical markers in accelerated agers. MAA could validly identify accelerated agers with higher risk of sarcopenia, whereas PhenoAge detected subclinical haematochemical alterations. Longitudinal studies are needed to appraise the validity of this newly introduced predictor of sarcopenia and verify if accelerated agers are at higher risk for developing sarcopenia.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine supplementation and protein restriction protect from organismal and brain aging independently.","authors":"YongTian Liang, Anja Krivograd, Sebastian J Hofer, Laxmikanth Kollipara, Thomas Züllig, Albert Sickmann, Tobias Eisenberg, Stephan J Sigrist","doi":"10.18632/aging.206267","DOIUrl":"https://doi.org/10.18632/aging.206267","url":null,"abstract":"<p><p>Brain aging and cognitive decline are significant biomedical and societal concerns. Both dietary restriction, such as limiting protein intake, and fasting, which restricts the timing of food consumption, have been proposed as strategies to delay aspects of aging. Recent studies suggest that intermittent fasting effects are mediated by the endogenous polyamine spermidine. Spermidine supplementation promotes mitochondrial integrity and functionality in aging brains by supporting hypusination of the translational initiation factor eIF5A. However, how molecular mechanisms underlying fasting mimicking interventions and protein restriction converge remain unclear, yet biomedically relevant. In this study, we combined low- and high-protein diets (2% versus 12% yeast in food) with spermidine supplementation in aging <i>Drosophila</i> fruit flies. Effective hypusination was essential for normal life expectancy on both 2% and 12% yeast diets. Spermidine supplementation increased longevity, protected against age-related locomotion decline on both diets and improved memory scores in older flies regardless of protein intake. Notably, spermidine did not reduce the positive effects of the 12% protein diet on fecundity. Our findings suggest that while both protein restriction and spermidine supplementation improve brain mitochondrial function, they largely operate through distinct mechanisms in modulating <i>Drosophila</i> brain aging. These results offer a basis for potential synergistic lifestyle interventions targeting age-related brain decline.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression.","authors":"Joseph Rupert, Zhanguo Gao, Yongmei Yu, Mikhail G Kolonin","doi":"10.18632/aging.206268","DOIUrl":"https://doi.org/10.18632/aging.206268","url":null,"abstract":"<p><p>The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We generated genetic <i>Tert</i> knockout (KO) mice driven by the <i>LysM</i> promoter in myeloid cells, by the <i>Pdgfra or Pdgfrb</i> promoter in mesenchymal cells, and by the <i>Tie2e</i> promoter in endothelial cells. We compared the effect of the <i>Tert</i> KOs in syngeneic models of orthotopically grafted E0771 breast adenocarcinoma, RM1 prostate adenocarcinoma, and KPC pancreatic adenocarcinoma. Tumors in <i>LysM-Tert</i>-KO, <i>Pdgfra-Tert</i>-KO, and <i>Pdgfrb-Tert</i>-KO mice displayed increased myofibrogenesis and desmoplasia. Tumors in <i>Tie2e-Tert</i>-KO mice displayed endothelial abnormality and the strongest reduction in tumor vascularization. This was linked with increased HIF1a protein nuclear localization, indicative of hypoxia, and the highest protein expression of the glycolytic marker GLUT1 in cancer cells. KPC tumors displayed reduced epithelial cytokeratin-19 protein expression and reduced tumor growth in all <i>Tert</i> KO models. However, liver metastases of KPC cells were only observed for <i>Tie2e-Tert</i>-KO mice. We conclude that senescence of distinct cells in the TME has different effects on cancer progression and that endothelial cell function preservation is important in metastasis suppression.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DoliClock: a lipid-based aging clock reveals accelerated aging in neurological disorders.","authors":"Djakim Latumalea, Maximilian Unfried, Diogo Barardo, Jan Gruber, Brian K Kennedy","doi":"10.18632/aging.206266","DOIUrl":"https://doi.org/10.18632/aging.206266","url":null,"abstract":"<p><p>Aging is a multifaceted process influenced by intrinsic and extrinsic factors, with lipid alterations playing a critical role in brain aging and neurological disorders. This study introduces DoliClock, a lipid-based biological aging clock designed to predict the age of the prefrontal cortex using post-mortem lipidomic data. Significant age acceleration was observed in autism, schizophrenia, and Down syndrome. Additionally, an increase in entropy around age 40 suggests dysregulation of the mevalonate pathway and dolichol accumulation. Dolichol, a lipid integral to N-glycosylation and intracellular transport, emerged as a potential aging biomarker, with specific variants such as dolichol-19 and dolichol-20 showing unique age-related associations. These findings suggest that lipidomics can provide valuable insights into the molecular mechanisms of brain aging and neurological disorders. By linking dolichol levels and entropy changes to accelerated aging, this study highlights the potential of lipid-based biomarkers for understanding and predicting biological age, especially in conditions associated with premature aging.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis reveals metabolic disruptions in cardiac tissues of aging nonhuman primates with spontaneous type 2 diabetes.","authors":"Yaowen Liu, Jingning Yu, Hao Hu, Shaoxia Pu, Haiyan Wu, Yunyu Ma, Wenhui Yang, Chongye Fang, Fei Sun, Haizhen Wang","doi":"10.18632/aging.206261","DOIUrl":"https://doi.org/10.18632/aging.206261","url":null,"abstract":"<p><strong>Background: </strong>The complex interplay between type 2 diabetes (TM) and obesity, particularly in aging populations, is increasingly recognized for its significant contribution to cardiac dysfunction. However, the metabolic changes within cardiac tissues that underlie this relationship remain poorly understood.</p><p><strong>Methods: </strong>We employed a multi-omics approach to investigate the metabolic alterations in cardiac tissues of aging nonhuman primates with spontaneous TM and obesity. Comprehensive analysis was conducted on left ventricular heart tissues from control (CON), obesity (OB), and TM groups, each comprising three aging monkeys. Proteomic data were analyzed using label-free mass spectrometry, and lipidomic profiles were determined using targeted metabolomic assays.</p><p><strong>Results: </strong>Our analysis uncovered significant metabolic perturbations in both the OB and TM groups relative to controls. Notably, the TM group showed alterations in cardiac metal ion metabolic proteins and a disruption in the liver-heart crosstalk, suggesting a derailment in the heart's metabolic support system. This was further exacerbated by reduced levels of short-chain acylcarnitines and lysophosphatidylcholines (lysoPCs), coupled with an increase in C18:2 acylcarnitines. A progressive decline in amino acid levels was observed from the control to OB to TM groups, indicating a stepwise deterioration in cardiac metabolic remodeling.</p><p><strong>Conclusions: </strong>This multi-omics study in aging nonhuman primates provides novel insights into the metabolic dysregulations associated with TM and obesity in cardiac tissues. The observed metabolic changes highlight potential therapeutic targets for prevention or mitigating the cardiac complications of TM.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for: EpiAge: a next-generation sequencing-based <i>ELOVL2</i> epigenetic clock for biological age assessment in saliva and blood across health and disease.","authors":"David Cheishvili, Sonia Do Carmo, Filippo Caraci, Margherita Grasso, A Claudio Cuello, Moshe Szyf","doi":"10.18632/aging.206263","DOIUrl":"10.18632/aging.206263","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 5","pages":"1368"},"PeriodicalIF":3.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for: D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway.","authors":"Xingxing Xu, Xiya Shen, Wenjin Feng, Danlu Yang, Lingting Jin, Jiaojiao Wang, Mianxian Wang, Zhang Ting, Feng Xue, Jingjing Zhang, Chaobo Meng, Roumeng Chen, Xinru Zheng, Leilei Du, Lina Xuan, Ying Wang, Tian Xie, Zhihui Huang","doi":"10.18632/aging.206264","DOIUrl":"10.18632/aging.206264","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 5","pages":"1369-1370"},"PeriodicalIF":3.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}