Aging-Us最新文献

{"title":"Dietary polyphenol assessment for aging research.","authors":"Ryan Bradley, Kara Fitzgerald, Romilly Hodges, Jamie L Villanueva","doi":"10.18632/aging.206252","DOIUrl":"10.18632/aging.206252","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1080-1081"},"PeriodicalIF":3.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082188","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":"Age-associated changes in the heart: implications for COVID-19 therapies.","authors":"Colby Wood, Wm Zachary Salter, Isaiah Garcia, Michelle Nguyen, Andres Rios, Jacqui Oropeza, Destiny Ugwa, Upasana Mukherjee, Ujala Sehar, P Hemachandra Reddy","doi":"10.18632/aging.206251","DOIUrl":"10.18632/aging.206251","url":null,"abstract":"<p><p>Cardiac aging involves progressive structural, functional, cellular, and molecular changes that impair heart function. This review explores key mechanisms, including oxidative stress, mitochondrial dysfunction, impaired autophagy, and chronic low-grade inflammation. Excess reactive oxygen species (ROS) damage heart muscle cells, contributing to fibrosis and cellular aging. Mitochondrial dysfunction reduces energy production and increases oxidative stress, accelerating cardiac decline. Impaired autophagy limits the removal of damaged proteins and organelles, while inflammation activates signaling molecules that drive tissue remodeling. Gender differences reveal estrogen's protective role in premenopausal women, with men showing greater susceptibility to heart muscle dysfunction and injury. After menopause, women lose this hormonal protection, increasing their risk of cardiovascular conditions. Ethnic disparities, particularly among underserved minority populations, emphasize how social factors such as access to care, environment, and chronic stress contribute to worsening cardiovascular outcomes. The coronavirus disease pandemic has introduced further challenges by increasing the incidence of heart damage through inflammation, blood clots, and long-term heart failure, especially in older adults with existing metabolic conditions like diabetes and high blood pressure. The virus's interaction with receptors on heart and blood vessel cells, along with a weakened immune response in older adults, intensifies cardiac aging. Emerging therapies include delivery of therapeutic extracellular vesicles, immune cell modulation, and treatments targeting mitochondria. In addition, lifestyle strategies such as regular physical activity, nutritional improvements, and stress reduction remain vital to maintaining cardiac health. Understanding how these biological and social factors intersect is critical to developing targeted strategies that promote healthy aging of the heart.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1340-1367"},"PeriodicalIF":3.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082184","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":"Frailty transitions in electronic health records: who first? what first?","authors":"Fabienne Hershkowitz Sikron, Rony Schenker, Orit Shahar, Achinoam Ben Akiva-Maliniak, Galit Segal, Yishay Koom, Idit Wolf, Bawkat Mazengya, Maor Lewis, Tzippy Shochat, Dov Albukrek","doi":"10.18632/aging.206247","DOIUrl":"10.18632/aging.206247","url":null,"abstract":"<p><strong>Background: </strong>Frailty is associated with an increased risk of adverse health outcomes and may worsen over time.</p><p><strong>Objectives: </strong>This study aims to describe the dynamic trajectory of frailty, identify the characteristics of those who deteriorate first, and determine what deteriorates first.</p><p><strong>Study design and setting: </strong>A primary care longitudinal population-based cohort with repeated measures at baseline and one year later.</p><p><strong>Participants: </strong>The cohort included all 119,952 Meuhedet members aged 65 years and over as of January 2023.</p><p><strong>Predictors: </strong>Demographic factors, health indicators, and the Meuhedet Electronic Frailty Index containing 36 deficits.</p><p><strong>Outcomes: </strong>Worsening frailty is defined as a higher frailty level one year later in 2024 compared to 2023. A new frailty deficit is defined as a deficit appearing in 2024 that was not present in 2023.</p><p><strong>Statistical analysis: </strong>The comparison of worsening percentages by demographic and clinical characteristics was tested using the chi-square test at the univariable level and logistic regression at the multivariable level.</p><p><strong>Results: </strong>Overall, 13.3% of participants worsened after one year of follow-up, with 2.3% dying. Higher risk groups for worsening included females, older individuals, those belonging to the Arab sector, and those with multimorbidity. New deficits mainly included modifiable risk factors related to general health and functionality, despite chronic diseases being more frequent at baseline.</p><p><strong>Conclusions: </strong>Emphasizing intervention programs based on these health promotion issues may significantly impact disease control and slow frailty worsening.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1148-1163"},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082192","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":"Role of apolipoprotein E (ApoE) ε4 in cognitive impairment after a stroke: a prospective cohort study.","authors":"Jia-Hung Chen, Lung Chan, Chien-Tai Hong, Chaur-Jong Hu, Yi-Chen Hsieh","doi":"10.18632/aging.206248","DOIUrl":"10.18632/aging.206248","url":null,"abstract":"<p><p>Although apolipoprotein E (ApoE) ε4 is a well-established risk factor for Alzheimer disease, its role in the development of post-stroke cognitive impairment (PSCI) remains uncertain. In this prospective cohort study, we recruited patients aged ≥20 years who had ischemic stroke within the past 7 days and measured their ApoE genotype. Baseline characteristics, including age, sex, education level, medical history, stroke severity, stroke etiology, and neuroimaging findings were recorded. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating (CDR) at 3 and 12 months post-stroke, with PSCI defined as a MoCA score < 26. After adjusting for confounding factors, the ApoE ε4 allele was not associated with the risk of PSCI at 3 or 12 months post-stroke. Other factors, including age, body mass index, education level, and initial stroke severity, were found to be associated with the risk of PSCI at 3 months. In patients who developed PSCI at 12 months, only education level and the MoCA score at 3 months were significantly associated with the risk of PSCI. Our findings suggest that, aside from traditional risk factors, the ApoE ε4 allele does not contribute to the risk of PSCI at 3 or 12 months post-stroke. Further studies with a larger sample size and longer follow-up are warranted.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1261-1274"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013826","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":"Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis.","authors":"Yi-Fan Chen, Yuan-Chi Teng, Jian-Hsin Yang, Cheng-Heng Kao, Ting-Fen Tsai","doi":"10.18632/aging.206249","DOIUrl":"10.18632/aging.206249","url":null,"abstract":"<p><p>Connection and crosstalk among the organelles critically contribute to cellular functions. Destruction of any kind of organelle is likely to induce a series of intracellular disorders and finally lead to cell death. Because of its subcellular locations, CDGSH iron-sulfur domain-containing protein 1 (Cisd1) and Cisd2 have functions that are related to maintaining mitochondria and ER homeostasis. As previous reports have shown, Cisd2 knockout mice have a decreased body weight and poor survival rate, and the primary defects were conducted in skeletal muscle. Our previous findings indicated that Cisd1 deletion causes a range of skeletal muscle defects in mice with Cisd2 deficiency, including mitochondrial degeneration, endoplasmic reticulum (ER) stress, and alteration of protein process, as well as programmed cell death. In Cisd1 and Cisd2 deficient condition, the whole of the protein biosynthesis was damaged, including translation, modification, transport, and degradation. Changes in the immune response, redox regulation, and metabolism were also present in Cisd1 and Cisd2 double knockout mice. Overall, we have demonstrated that Cisd1 and Cisd2 knockout have a synergistic effect on skeletal muscles, and that Cisd2 plays a more critical role than Cisd1. These synergistic effects impact signaling regulation and interrupt the crosstalk and homeostasis of organelles. This creates severe disorders in various tissues and organs.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1275-1297"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042624","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":"Methylation clocks for evaluation of anti-aging interventions.","authors":"Josh Mitteldorf","doi":"10.18632/aging.206245","DOIUrl":"10.18632/aging.206245","url":null,"abstract":"<p><p>Methylation clocks have found their way into the community of aging research as a way to test anti-aging interventions without having to wait for mortality statistics. But methylation is a primary means of epigenetic control, and presumably has evolved under strong selection. Hence, if methylation patterns change consistently at late ages it must mean one of two things. Either (1) the body is evolved to destroy itself (with inflammation, autoimmunity, etc.), and the observed methylation changes are a means to this end; or (2) the body detects accumulated damage, and is ramping up repair mechanisms in a campaign to rescue itself. My thesis herein is that both Type 1 and Type 2 changes are occurring, but that only Type 1 changes are useful in constructing methylation clocks to evaluate anti-aging interventions. This is because a therapy that sets back Type 1 changes to an earlier age state has stopped the body from destroying itself; but a therapy that sets back Type 2 changes has stopped the body from repairing itself. Thus, a major challenge before the community of epigenetic clock developers is to distinguish Type 2 from Type 1. The existence of Type 1 epigenetic changes is in conflict with conventional Darwinian thinking, and this has prompted some researchers to explore the possibility that Type 1 changes might be a form of stochastic epigenetic drift. I argue herein that what seems like directed epigenetic change really is directed epigenetic change. Of five recent articles on \"stochastic methylation clocks,\" only one (from the Conboy lab) is based on truly stochastic changes. Using the Conboy methodology and a methylation database, I construct a measure of true methylation drift, and show that its correlation with age is too low to be useful.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1082-1090"},"PeriodicalIF":3.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045805","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":"<i>APOE</i> genotype and biological age impact inter-omic associations related to bioenergetics.","authors":"Dylan Ellis, Kengo Watanabe, Tomasz Wilmanski, Michael S Lustgarten, Andres V Ardisson Korat, Gwênlyn Glusman, Jennifer Hadlock, Oliver Fiehn, Paola Sebastiani, Nathan D Price, Leroy Hood, Andrew T Magis, Simon J Evans, Lance Pflieger, Jennifer C Lovejoy, Sean M Gibbons, Cory C Funk, Priyanka Baloni, Noa Rappaport","doi":"10.18632/aging.206243","DOIUrl":"10.18632/aging.206243","url":null,"abstract":"<p><p>Apolipoprotein E (<i>APOE</i>) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In the present study, we analyzed multi-omic association patterns across <i>APOE</i> genotypes, sex, and biological age (BA) axes in 2,229 community dwelling individuals. Our analysis, supported by validation in an independent cohort, identified diacylglycerols as the top <i>APOE</i>-associated plasma metabolites. However, despite the known opposing aging effects of the allele variants, both ε2- and ε4-carriers showed higher diacylglycerols compared to ε3-homozygotes. 'Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites. These results demonstrate the context-dependence of the influence of <i>APOE</i>, with ε2 potentially strengthening insulin resistance-like pathways in the decades prior to imparting its longevity benefits. Additionally, they provide an atlas of <i>APOE</i>-related 'omic associations and support the involvement of bioenergetic pathways in mediating the impact of <i>APOE</i> on aging.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1105-1138"},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050770","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":"Oxytocin modulates insulin and GLP-1 secretion in pancreatic islets.","authors":"Kasumi Hattori, Masaru Shimizu, Megumi Yamachi, Kiichi Tezuka, Toru Fukushima, Syoko Yokota, Tatsuya Okano, Shingen Misaka, Shizu Hidema, Kazuaki Kanai, Kenju Shimomura, Yuko Maejima","doi":"10.18632/aging.206244","DOIUrl":"10.18632/aging.206244","url":null,"abstract":"<p><strong>Objective: </strong>Oxytocin (Oxt) is secreted to the peripheral body through the pituitary gland and can induce insulin secretion under high glucose conditions. Insulin secretion is regulated by various factors including glucagon-like peptide (GLP)-1, secreted from intestinal L-cells. GLP-1 is also expressed and secreted within islets and termed as \"intra-islet GLP-1\". The study aims to elucidate the impact of Oxt on insulin secretion in relation to intra-islet GLP-1.</p><p><strong>Methods: </strong>We measured changes in blood glucose and insulin levels following Oxt administration in wild-type (WT) and Oxt receptor knockout (OxtR KO) mice. Additionally, we assessed insulin secretion from islets isolated from WT and OxtR KO mice under conditions with and without Oxt. Histological analysis of OxtR expression in islets was performed. The effects of Oxt on factors influencing insulin secretion, such as glucagon, GLP-1 secretion from WT islets and K_ATP channel activity were also investigated.</p><p><strong>Results: </strong>Oxt injection induced a temporal rise in blood glucose levels in both WT and OxtR-KO mice at 15-min post-injection. In WT mice, blood glucose level returned to control levels by 30min and were significantly lower at 60-min. OxtR KO mice maintained elevated glucose levels at 30-min. WT mice showed a significant increase in insulin levels at 15-min, while OxtR KO mice did not. OxtR was expressed in both insulin and glucagon-positive cells with higher expression in glucagon-positive cells. WT islets showed an increase in intra-islet GLP-1 secretion upon Oxt application.</p><p><strong>Conclusions: </strong>The study indicates that Oxt may enhance insulin secretion by promoting the secretion of intra-islet GLP-1.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"1139-1147"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000484","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":"Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.","authors":"Arjun Sapkota, Sebok K Halder, Richard Milner","doi":"10.18632/aging.206241","DOIUrl":"10.18632/aging.206241","url":null,"abstract":"<p><p>Chronic mild hypoxia (CMH; 8% O₂) triggers transient blood-brain barrier (BBB) disruption, an effect greatly increased with age. As BBB disruption predisposes to neuronal death and cognitive decline, here we defined the hypoxic thresholds that trigger BBB breakdown in young and aged mice, and then defined the age at which hypoxia-induced BBB disruption significantly increases. Dual-immunofluorescence of brain sections demonstrated that the thresholds required to trigger hypoxia-induced BBB disruption (CD31/fibrinogen) and endothelial proliferation (CD31/Ki67) were much lower in aged mice (15% O₂) compared to young (13% O₂). Hypoxia-induced endothelial proliferation was relatively constant across the age range, but advanced age strongly enhanced the degree of BBB disruption (4-6-fold greater in 23 months vs. 2 months old). While the BBB became more vulnerable to hypoxic disruption at 12-15 months, a large step-up also occurred at the surprisingly young age 2-6 months. Our data demonstrates that the aged BBB is far more sensitive to hypoxia-induced BBB disruption than the young and define the hypoxic thresholds that trigger hypoxia-induced BBB disruption in young and aged mice. This information has translational implications for people exposed to hypoxia and for those living with hypoxia-associated conditions such as asthma, emphysema, ischemic heart disease, and apnea.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"1091-1104"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036222","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 2 for: Taurine suppresses ROS-dependent autophagy via activating Akt/mTOR signaling pathway in calcium oxalate crystals-induced renal tubular epithelial cell injury.","authors":"Yan Sun, Shiting Dai, Jin Tao, Yunlong Li, Ziqi He, Quan Liu, Jiawen Zhao, Yaoliang Deng, Juening Kang, Xuepei Zhang, Sixing Yang, Yunlong Liu","doi":"10.18632/aging.206246","DOIUrl":"10.18632/aging.206246","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 4","pages":"1073-1074"},"PeriodicalIF":3.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007787","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}