IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-21 DOI: 10.18632/aging.206254

Samuel Fernández-Carnero, Oliver Martínez-Pozas, Daniel Pecos-Martín, Armando Pardo-Gómez, Juan Nicolás Cuenca-Zaldívar, Eleuterio A Sánchez-Romero

{"title":"Update on the detection of frailty in older adults: a multicenter cohort machine learning-based study protocol.","authors":"Samuel Fernández-Carnero, Oliver Martínez-Pozas, Daniel Pecos-Martín, Armando Pardo-Gómez, Juan Nicolás Cuenca-Zaldívar, Eleuterio A Sánchez-Romero","doi":"10.18632/aging.206254","DOIUrl":"https://doi.org/10.18632/aging.206254","url":null,"abstract":"Background: This study aims to investigate the relationship between muscle activation variables assessed via ultrasound and the comprehensive assessment of geriatric patients, as well as to analyze ultrasound images to determine their correlation with morbimortality factors in frail patients.Methods: The present cohort study will be conducted in 500 older adults diagnosed with frailty. A multicenter study will be conducted among the day care centers and nursing homes. This will be achieved through the evaluation of frail older adults via instrumental and functional tests, along with specific ultrasound images to study sarcopenia and nutrition, followed by a detailed analysis of the correlation between all collected variables.Discussion: This study aims to investigate the correlation between ultrasound-assessed muscle activation variables and the overall health of geriatric patients. It addresses the limitations of previous research by including a large sample size of 500 patients and measuring various muscle parameters beyond thickness. Additionally, it aims to analyze ultrasound images to identify markers associated with higher risk of complications in frail patients. The study involves frail older adults undergoing functional tests and specific ultrasound examinations. A comprehensive analysis of functional, ultrasound, and nutritional variables will be conducted to understand their correlation with overall health and risk of complications in frail older patients.Trial registration: The study was approved by the Research Ethics Committee of the Hospital Universitario Puerta de Hierro, Madrid, Spain (Act nº 18/2023). In addition, the study was registered with https://clinicaltrials.gov/ (NCT06218121).","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144536","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}

引用次数: 0

Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations. 短期适度的热量限制在恒河猴减弱卵巢老化的标记在选定的人群。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-20 DOI: 10.18632/aging.206253

Emma S Gargus, Rhea Sharma, Rebecca Gu, Camille Mulcahy, Brian W Johnson, Jing Song, Jungwha Lee, Mary Zelinski, Francesca E Duncan

{"title":"Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations.","authors":"Emma S Gargus, Rhea Sharma, Rebecca Gu, Camille Mulcahy, Brian W Johnson, Jing Song, Jungwha Lee, Mary Zelinski, Francesca E Duncan","doi":"10.18632/aging.206253","DOIUrl":"https://doi.org/10.18632/aging.206253","url":null,"abstract":"Ovarian aging results in decreased fertility and endocrine function. In mice, caloric restriction (CR) maintains ovarian function. In this study, we determined whether CR also has a beneficial effect on reproductive longevity in the nonhuman primate (NHP). Ovaries were collected from young (10-13 years) and old (19-26 years) rhesus macaques who were either on a diet of moderate caloric restriction or a control diet for three years. To test the effect of CR on follicle number, follicles were analyzed in histological sections from animals across experimental cohorts: Young Control, Young CR, Old Control, Old CR (n = 4-8/group). In control animals, there was an age-dependent decrease in follicle numbers across all follicle stages (P < 0.05). Although there was no effect of diet on total follicle number, the follicle distribution in the Old CR cohort more closely resembled that of young animals. The subset of Old CR animals that were still cycling, albeit irregularly, had more primordial follicles than controls (P < 0.05). Assessment of collagen and hyaluronic acid matrices revealed that CR attenuated age-related changes to the ovarian microenvironment. Overall, CR may improve aspects of reproductive longevity in the NHP, but the timing of when it occurs during the reproductive lifespan is likely critical.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144535","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}

引用次数: 0

The aspartate superpathway in gut microbiota-related metabolic pathways mediates immune cell protection against COPD and IPF: a Mendelian randomization analysis. 肠道微生物群相关代谢途径中的天冬氨酸超途径介导免疫细胞对COPD和IPF的保护：孟德尔随机分析

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-15 DOI: 10.18632/aging.206250

Lei Chen, Haoyan Chen, Qin Li, Jun Ma, Yanzhi Feng, Shenghua Zhang, Yu Han, Jie Pan, Mingjiong Zhang, Kai Sun, Shuangshuang Wu

{"title":"The aspartate superpathway in gut microbiota-related metabolic pathways mediates immune cell protection against COPD and IPF: a Mendelian randomization analysis.","authors":"Lei Chen, Haoyan Chen, Qin Li, Jun Ma, Yanzhi Feng, Shenghua Zhang, Yu Han, Jie Pan, Mingjiong Zhang, Kai Sun, Shuangshuang Wu","doi":"10.18632/aging.206250","DOIUrl":"https://doi.org/10.18632/aging.206250","url":null,"abstract":"Background: Both genetic and environmental factors can influence idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) development. The gut microbiota plays crucial roles in maintaining tissue homeostasis. Dysregulation of the gut microbiota can result in disease. However, whether the alteration of the gut microbiota influences IPF and COPD remains unknown.Research question: What is the causal relationship between IPF, COPD and the gut microbiota-related metabolic pathways? What are the potential intermediate mediators in this relationship?Study design and methods: Intersect the gut microbiota and its metabolic pathways associated with IPF and COPD. Utilizing summary data from GWAS in public databases, a two-sample Mendelian randomization (MR) analysis was conducted on the gut microbiota-related metabolic pathway, the aspartate superpathway, in relation to IPF and COPD. Furthermore, we employed a two-step MR to quantify the proportion of influence mediated by monocytes and cDCs on the aspartate superpathway in relation to IPF and COPD.Results: The MR analysis found that the aspartate superpathway decreased the risk of developing IPF and COPD. Monocytes and cDCs acted as intermediary substances, participating in this with influence proportions of 7.88% and 6.27%, respectively.Interpretation: There is a causal link between the gut microbiota-related metabolic pathway, the aspartate superpathway, and IPF and COPD, where the influence is partially mediated by monocytes and cDCs. In clinical practice, we increase the focus on gut microbiota-mediated immune cells in relation to IPF and COPD.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082196","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}

引用次数: 0

Dietary polyphenol assessment for aging research. 膳食多酚对衰老的评价研究。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-13 DOI: 10.18632/aging.206252

Ryan Bradley, Kara Fitzgerald, Romilly Hodges, Jamie L Villanueva

引用次数: 0

Age-associated changes in the heart: implications for COVID-19 therapies. 心脏年龄相关变化：对COVID-19治疗的影响

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-13 DOI: 10.18632/aging.206251

Colby Wood, Zach Saltera, Isaiah Garcia, Michelle Nguyen, Andres Rios, Jacqui Oropeza, Destiny Ugwa, Upasana Mukherjee, Ujala Sehar, P Hemachandra Reddy

{"title":"Age-associated changes in the heart: implications for COVID-19 therapies.","authors":"Colby Wood, Zach Saltera, Isaiah Garcia, Michelle Nguyen, Andres Rios, Jacqui Oropeza, Destiny Ugwa, Upasana Mukherjee, Ujala Sehar, P Hemachandra Reddy","doi":"10.18632/aging.206251","DOIUrl":"https://doi.org/10.18632/aging.206251","url":null,"abstract":"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.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frailty transitions in electronic health records: who first? what first? 电子健康记录中的虚弱转变：谁先出现？第一次什么?

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-12 DOI: 10.18632/aging.206247

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

{"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":"https://doi.org/10.18632/aging.206247","url":null,"abstract":"Background: Frailty is associated with an increased risk of adverse health outcomes and may worsen over time.Objectives: This study aims to describe the dynamic trajectory of frailty, identify the characteristics of those who deteriorate first, and determine what deteriorates first.Study design and setting: A primary care longitudinal population-based cohort with repeated measures at baseline and one year later.Participants: The cohort included all 119,952 Meuhedet members aged 65 years and over as of January 2023.Predictors: Demographic factors, health indicators, and the Meuhedet Electronic Frailty Index containing 36 deficits.Outcomes: 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.Statistical analysis: 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.Results: 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.Conclusions: Emphasizing intervention programs based on these health promotion issues may significantly impact disease control and slow frailty worsening.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis. Cisd1与Cisd2协同作用，通过维持线粒体和内质网稳态来调节蛋白质加工。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-08 DOI: 10.18632/aging.206249

Yi-Fan Chen, Yuan-Chi Teng, Jian-Hsin Yang, Cheng-Heng Kao, Ting-Fen Tsai

{"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":"https://doi.org/10.18632/aging.206249","url":null,"abstract":"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.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of apolipoprotein E (ApoE) ε4 in cognitive impairment after a stroke: a prospective cohort study. 载脂蛋白E (ApoE) ε4在脑卒中后认知功能障碍中的作用：一项前瞻性队列研究

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-08 DOI: 10.18632/aging.206248

Jia-Hung Chen, Lung Chan, Chien-Tai Hong, Chaur-Jong Hu, Yi-Chen Hsieh

{"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":"https://doi.org/10.18632/aging.206248","url":null,"abstract":"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.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylation clocks for evaluation of anti-aging interventions. 甲基化时钟用于评估抗衰老干预措施。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-05 DOI: 10.18632/aging.206245

Josh Mitteldorf

{"title":"Methylation clocks for evaluation of anti-aging interventions.","authors":"Josh Mitteldorf","doi":"10.18632/aging.206245","DOIUrl":"https://doi.org/10.18632/aging.206245","url":null,"abstract":"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.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

APOE genotype and biological age impact inter-omic associations related to bioenergetics. APOE基因型和生物年龄影响与生物能量学相关的组间关联。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-05-03 DOI: 10.18632/aging.206243

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

{"title":"APOE 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":"https://doi.org/10.18632/aging.206243","url":null,"abstract":"Apolipoprotein E (APOE) 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 APOE 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 APOE-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 APOE, with ε2 potentially strengthening insulin resistance-like pathways in the decades prior to imparting its longevity benefits. Additionally, they provide an atlas of APOE-related 'omic associations and support the involvement of bioenergetic pathways in mediating the impact of APOE on aging.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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