Aging-Us最新文献

{"title":"Exercise as a geroprotector: focusing on epigenetic aging.","authors":"Takuji Kawamura, Mitsuru Higuchi, Zsolt Radak, Yasuyuki Taki","doi":"10.18632/aging.206278","DOIUrl":"https://doi.org/10.18632/aging.206278","url":null,"abstract":"<p><p>Emerging evidence suggests that physical activity, exercise, and physical fitness may delay or reverse epigenetic aging, with implications for the extension of healthspan. This Perspective review defines essential exercise-related terminology and synthesizes findings from both human and animal studies examining the relationships between these factors and DNA methylation-based epigenetic clocks. While observational studies have demonstrated inverse relationships between cardiorespiratory fitness and epigenetic age acceleration, interventional studies further suggest that structured exercise training can induce epigenomic rejuvenation, particularly in blood and skeletal muscle. However, these effects exhibit considerable interindividual and organ-specific variability, underscoring the need for future research to elucidate causal mechanisms and organ-specific responses in order to optimize the application of exercise as a geroprotective intervention.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602348","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":"Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.","authors":"Su Yon Jung, Matteo Pellegrini, Xianglong Tan, Herbert Yu","doi":"10.18632/aging.206276","DOIUrl":"https://doi.org/10.18632/aging.206276","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic clocks, estimated via DNA methylation (DNAm), reflect individuals' biological aging in multiple tissues and are associated with age-related diseases, but their functional role in colorectal cancer (CRC), an age-associated disease, remains unconclusive. DNAm in tumor tissues exclusively exhibits cancerization with expansion of a stem cell pool, leading to the lowest DNAm age; this raises a question about its cancer predictability. Thus, the DNAm aging marker in pre-diagnostic peripheral blood leukocytes (PBLs) may provide key information on CRC etiology and prevention. We aim to examine pre-diagnostic epigenetic makers for aging in PBLs in association with CRC development and risk modification by lifestyles.</p><p><strong>Methods: </strong>Using data from a large cohort study of white postmenopausal women, we examined biological aging status in PBLs via three well-established epigenetic clocks-Horvath's, Hannum's and Levine's-and prospectively evaluated CRC development in relation to the aging markers and risk modification by lifestyle factors.</p><p><strong>Results: </strong>The epigenetic clocks strongly correlated with chronological age, and older DNAm age and age acceleration were significantly associated with increased risk for CRC. Women with bilateral oophorectomy before natural menopause had substantially higher risk for CRC development when they also had epigenetically accelerated aging phenotypes. Among women who maintained healthy dietary patterns, no apparently higher risk was found in those with accelerated aging compared with those with decelerated aging.</p><p><strong>Conclusions: </strong>Our findings contribute to better understanding of the role of a pre-diagnostic epigenetic aging biomarker and its interplay with lifestyles in CRC carcinogenesis, informing risk stratification strategies for aged individuals.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602347","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":"Frailty associates with respiratory exacerbations and mortality in the COPDGene cohort.","authors":"Eleanor Kate Phillips, Yichen Huang, Elizabeth Regan, Barry Make, Matthew Strand, Abebaw Mengistu Yohannes, Nicola A Hanania, Jessica Bon, Karin F Hoth, James D Crapo, Edwin K Silverman, Dawn L DeMeo","doi":"10.18632/aging.206275","DOIUrl":"https://doi.org/10.18632/aging.206275","url":null,"abstract":"<p><p>Frailty is associated with respiratory exacerbations and mortality in individuals with Chronic Obstructive Pulmonary Disease (COPD). Among those with a smoking history and normal spirometry, frailty's association with respiratory outcomes is less defined. COPDGene is a cohort study of individuals aged 45-80 with a minimum 10 pack-year smoking history. A modified Fried Frailty Phenotype was performed at 10-year follow-up; participants were categorized as frail, prefrail, or robust. Primary outcomes were respiratory exacerbations, epigenetic pace of aging, and all-cause mortality. Among 2665 participants, 401 (15%) were frail and 1352 (51%) were prefrail. Adjusting for smoking and lung function, frailty was associated with prospective respiratory exacerbation rate (IRR 3.4, 95% CI 2.4-4.8), severe exacerbations (OR 2.8(1.8-4.2)), and frequent exacerbations (OR 5.5(3.2-9.3)). Prefrailty was also associated with exacerbation outcomes (rate IRR 1.8(1.4-2.3); severe OR 1.6(1.1-2.2); frequent OR 2.6(1.7-4.1)). Frailty and prefrailty were associated with increased all-cause mortality (AHR: frailty 4.5(2.4-8.5); prefrailty 2.5(1.5-4.2)). All frailty (and most prefrailty) findings persisted in those with normal spirometry. Baseline DunedinPACE of aging was associated with prospective frailty at 10-year follow-up. Frailty associated with respiratory exacerbations and mortality; findings persisted among individuals with normal spirometry, highlighting the relevance of evaluating for frailty in people with a history of smoking.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577001","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":"Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.","authors":"Amparo Santamaria, Ana Ballester, Manuel Muñoz","doi":"10.18632/aging.206274","DOIUrl":"10.18632/aging.206274","url":null,"abstract":"<p><p>The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain. Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP). The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following <i>in vitro</i> fertilization (IVF) treatment. A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 6","pages":"1571-1580"},"PeriodicalIF":3.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531265","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":"Implications of the KHDC4-TRAF2 axis in the context of prostate cancer prognosis.","authors":"Su-Wei Hu, Chia-Chang Wu, Shao-Wei Dong, Kai-Yi Tzou, Chih-Heng Chen, Yuan-Hung Wang, Yen-Nien Liu, Chiao-Chun Liao, Chien-Hsiu Li","doi":"10.18632/aging.206273","DOIUrl":"10.18632/aging.206273","url":null,"abstract":"<p><p>The inability to effectively identify the formation of advanced-stage tumors poses a challenge in precisely determining when to intervene in prostate cancer (PCa). Despite the use of PSA as a screening factor, it still falls short in significantly improving the diagnosis and prognosis of advanced PCa. Identifying novel prognosis biomarkers to assist in confirming the progression of advanced PCa will contribute to more precise and effective therapeutic approaches. Through a comparative analysis between late-stage and early-stage TCGA-PRAD transcriptomes, KHDC4 has been identified as a key and specific member of the KHDC family that shows increased expression in PCa. The elevated levels of KHDC4 in late-stage and lymph node metastasis are positively correlated with poorer overall survival and disease-free survival rates in PCa patients. Simulated molecular regulation networks and <i>in vitro</i> results support the notion that the KHDC4-TRAF2 axis contributes to tumor malignancy features in late-stage and lymph node metastasis tumor samples, consequently correlating with worse progression-free interval and disease-free interval prognosis values in TCGA-PRAD. It is noteworthy that the positive correlation of the distribution of KHDC4 and TRAF2 with the Gleason score is superior to that of KLK3. Promoter analysis reveals that KHDC4 and TRAF2 share a similar upstream regulator, E2F4, for their transactivation. Molecular simulated profiles, mimicking downstream effectors under both KHDC4 and TRAF2 regulation, can be utilized as signatures for overall survival and disease-free survival prognosis purposes. In conclusion, this systematic analysis study indicates that the axis of KHDC4-TRAF2 may serve as a valuable prognostic model for evaluating advanced PCa.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1544-1570"},"PeriodicalIF":3.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499480","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":"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":"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":"1511-1520"},"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":"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":"1521-1543"},"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":"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":"1484-1510"},"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":"1466-1483"},"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":"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":"1429-1451"},"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}