The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Higher Circulating Alpha-Klotho Levels Increase All-Cause Mortality Through Mediation Effects of Liver Fibrosis: A Second Analysis of NHANES.","authors":"Kai Wei,Qing Zhang,Chun Chen,Yanping Yang,Shuimei Sun,Libin Wang,M S Xiaotong Chen,Xinhua Luo,Qi Chen","doi":"10.1093/gerona/glaf109","DOIUrl":"https://doi.org/10.1093/gerona/glaf109","url":null,"abstract":"BACKGROUNDLaboratory studies have demonstrated that mice with α-klotho gene deficiency experience a shortened lifespan, but epidemiological evidence linking circulating α-klotho levels and mortality remain inconclusive. This study aimed to examine the association between α-klotho and mortality and to explore how liver fibrosis mediate this association.METHODSThe participants were selected from the National Health and Nutrition Examination Survey from 2007 to 2016, who were followed up through December 31, 2019. Serum α-klotho was tested by an ELISA kit. Liver fibrosis was assessed using 3 validated noninvasive algorithms: FIB-4, NFS, and APRI. Weighted Cox regression analyses, restricted cubic spline regression and mediation analyses were employed.RESULTSThroughout the follow-up period of a median of 92 [62, 122] months, the lowest and highest quintiles both showed an increased risk of all-cause mortality (hazard ratio, lowest quintile: 1.367; 95% CI: 1.125-1.661; hazard ratio, highest quintile: 1.210; 95% CI: 1.008-1.452) compared with the intermediate α-klotho quintiles. The association between α-klotho and the risk of all-cause mortality revealed a U-shaped curve (P for nonlinearity < 0.001), with an inflection point of α-klotho (log-transformed) of 6.917. The FIB-4, NFS, and APRI explained 31.85%, 27.74%, and 25.50%, respectively, of the relationships between higher α-klotho levels and all-cause mortality among individuals whose α-klotho levels were greater than the inflection point.CONCLUSIONSThis study verified a U-shaped association between α-klotho and all-cause mortality in the US general population. Moreover, higher α-klotho levels were associated with an increased risk of death, partially due to liver fibrosis mediating this association.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foundations and Strategic Vision of the Canadian Translational Geroscience Network.","authors":"Guy Hajj-Boutros,Andréa Faust,John Muscedere,Perry Kim,Gilles Gouspillou,Lea Harrington,James L Kirkland,George A Kuchel,Jeremy Van Raamsdonk,R Jane Rylett,Chantal Autexier,Louis R Lapierre,Michael Kobor,Mohammad Auais,Ann Beliën,Jeroen Aerssens,George Sutphin,Kenneth Rockwood,Alexandra Papaioannou,Marc Sim,Jamie Justice,Nancy Mayo,Gustavo Duque","doi":"10.1093/gerona/glaf111","DOIUrl":"https://doi.org/10.1093/gerona/glaf111","url":null,"abstract":"Geroscience is an emerging interdisciplinary field that explores the biological connections between aging and the development of chronic diseases, with the ultimate goal of identifying interventions to extend healthspan and delay age-related conditions. Recognizing the growing importance of this field, the Canadian Translational Geroscience Network (CTGN, geroscience.ca) was officially launched during a conference held in Montreal on September 5-6, 2024. Building on the momentum of successful Geroscience meetings in Toronto and Montreal in 2023, this milestone event marked a transformative step forward for geroscience in Canada. This event brought together key stakeholders, including the Canadian Frailty Network (CFN), the Canadian Institutes of Health Research Institute of Aging (CIHR-IA), the Réseau Québécois de Recherche sur le Vieillissement (RQRV), the Simone & Edouard Schouela RUISSS McGill Centre of Excellence for Sustainable Health of Seniors (Schouela CEDurable), the Division of Geriatric Medicine at McGill University, and the Department of Biochemistry at the University of Toronto. Additionally, a broad coalition of geriatricians, healthcare professionals, and researchers convened to discuss and advance the field of geroscience in Canada. The two-day conference focused on creating a multidisciplinary community to address the challenges of an aging population, emphasizing the importance of funding, national and international collaboration, and training the next generation of researchers and clinicians. Workshops and presentations showcased a range of innovative research, from cellular studies to clinical trials, aimed at understanding and treating age-related diseases. Key discussions highlighted the critical role of partnerships among research institutions, healthcare systems, and biotech companies in translating research findings into practical interventions. The CTGN's strategic objectives focus on expanding funding opportunities for geroscience, developing specialized training programs, and increasing membership to cultivate a diverse, multidisciplinary, and collaborative network. This network aims to include students, basic and clinical researchers, citizens, government entities, and organizations or professionals interested in advancing the geroscience field. With a clear roadmap for future growth, the CTGN aims to position Canada at the forefront of geroscience, fostering evidence-based innovation that improves the health and quality of life for aging populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive stability among plasma p-tau 181 negative individuals: a 5-year analysis of the MAPT study.","authors":"Federico Bellelli,Philipe De Souto Barreto,Christelle Cantet,Pierre Jean Ousset,Kaj Blennow,Bruno Vellas,Davide Angioni,","doi":"10.1093/gerona/glaf113","DOIUrl":"https://doi.org/10.1093/gerona/glaf113","url":null,"abstract":"BACKGROUNDThis study aims to assess the evolution of cognitive performances over a five-year follow-up period in community-dwelling older people with negative plasma p-tau181 levels and to determine whether frailty could discriminate between those who experience cognitive decline and those who do not, in the p-tau negative groups.METHODSThis is a five-year analysis of the Multidomain Alzheimer Prevention Trial (MAPT) testing cognitive evolution among 503 community-dwelling individuals with available data on plasma p-tau181. Negative p-tau status was assigned according to three different cut-offs: amyloid-PET positivity (9·6 pg/mL), highest tertile for baseline p-tau181 distribution (10·9 pg/mL) and Alzheimer's Disease (AD) diagnosis prediction (12·4 pg/mL) cut-offs. Cognition was measured using a validated composite cognitive score (CCS) derived from the Z-scores of four cognitive tests. Longitudinal changes from baseline in the CCS according to plasma p-tau181 status were compared using linear mixed models.RESULTSIn a population with an end-of-study median age of 79 years (IQR: 76-82), whatever the cut-off, the overall group with negative p-tau181 status did not develop cognitive decline over the follow-up. Among the p-tau181 negative groups, individuals who declined had a higher prevalence of frailty compared to those who did not decline.CONCLUSIONSCognitive performance in older people with negative plasma p-tau181 levels remains stable over a five-year period. This may suggest that older age alone, in the absence of positive biomarkers for brain pathology (or frailty), is not associated with cognitive decline. Frailty may increase vulnerability to the neuropathological burden associated with AD.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of Metformin vs Sulfonylureas on Exceptional Longevity in Women with Type 2 Diabetes: Target Trial Emulation","authors":"Aladdin H Shadyab, Mark A Espeland, Andrew O Odegaard, JoAnn E Manson, Bernhard Haring, Karen C Johnson, Zhao Chen, Bowei Zhang, Andrea Z LaCroix","doi":"10.1093/gerona/glaf095","DOIUrl":"https://doi.org/10.1093/gerona/glaf095","url":null,"abstract":"Background The association of metformin with mortality has been mixed, and no prior study has determined whether metformin initiation is associated with exceptional longevity, defined as survival to ages 90 and older. Methods We performed a new-user, active comparator cohort study using the target trial emulation framework among the Women’s Health Initiative cohort to determine whether metformin versus sulfonylurea initiation was associated with exceptional longevity (survival to age 90). We identified participants ≥60 years with incident type 2 diabetes and no history of hypoglycemic agents or insulin prior to treatment initiation to perform intention-to-treat analyses. We used 1:1 propensity score matching on demographic characteristics, lifestyle behaviors, diabetes duration, comorbidities (hypertension, cardiovascular disease, chronic obstructive pulmonary disease, and cancer), body mass index, and concomitant medications to balance treatment groups on key confounders. Results Among 438 propensity score-matched women with type 2 diabetes, the incidence rate of death before age 90 per 100 person-years in women initiating metformin monotherapy was 3.7 (95% CI 3.1-4.4) compared with 5.0 (95% CI 4.2-5.8) for sulfonylurea monotherapy. The adjusted risk of death before age 90 was 30% lower for initiation of metformin monotherapy versus sulfonylurea monotherapy (HR, 0.70; 95% CI, 0.56-0.88). Conclusions In this first target trial emulation of metformin and exceptional longevity, we found that metformin initiation increased exceptional longevity compared with sulfonylurea initiation among women with type 2 diabetes. Because this comparison was not made to placebo in an RCT and given the observational design with potential for residual confounding, causality cannot be inferred.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Immune Cell Subsets with Longevity: The Cardiovascular Health Study","authors":"Sylvie Dobrota Lai, Petra Buzkova, Joseph A Delaney, Nels Olson, Bruce M Psaty, Sally A Huber, Margaret F Doyle, Russell P Tracy, Michelle C Odden","doi":"10.1093/gerona/glaf094","DOIUrl":"https://doi.org/10.1093/gerona/glaf094","url":null,"abstract":"Background Changes in the immune system are a potential biological mechanism of aging. We investigated the association of circulating immune cell subsets with age at death and survival to age 90. Methods Immune cell phenotypes were measured at baseline in 1,625 adults, aged 70 to 85 years, in the Cardiovascular Health Study. We selected five primary immune cell subsets: gamma-delta T-cells, natural killer cells, CD8+ T effector memory CD45RA expressing cells (TEMRA) cells, ratio of CD4+ to CD8+ cells, and ratio of naïve to memory CD8+ cells. We used linear regression and Poisson models, adjusting for demographics and clinical factors; and tested for effect modification by sex and race. In a secondary analysis, we investigated 23 additional immune cell subsets, using the Holm-Bonferroni method to adjust for multiple comparisons. Results No primary immune cell subsets were significantly associated with longevity. Two secondary subsets were significantly associated with age at death. Each SD higher proportion of CD4+CD57+ cells was associated with a 0.64-year earlier death (95%CI:-0.99,-0.30) and each SD higher proportion of CD4+CD28-CD57+ cells was associated with a 0.54-year earlier death (95% CI:-0.87,-0.21). Several subsets had significant interactions with sex and race in the fully adjusted model of age at death. A higher proportion of CD4+CD57+ T-cells was significantly associated with lower likelihood of survival to age 90 (RR: 0.79) and 1.07-year earlier age at death in males, but not in females. Conclusions Our results suggest that CD4+CD57+ cells are associated with earlier death and this relationship was stronger in males than females.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of ADRD plasma biomarkers with mobility in cognitively unimpaired older adults","authors":"Atalie C Thompson, Xiaoyan Leng, Michael E Miller, Thomas C Register, Paul J Laurienti, Michelle M Mielke, Suzanne Craft, Stephen B Kritchevsky","doi":"10.1093/gerona/glaf110","DOIUrl":"https://doi.org/10.1093/gerona/glaf110","url":null,"abstract":"BACKGROUND Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer’s disease and related dementias (ADRD) may be associated with mobility performance in older adults who are cognitively unimpaired. METHODS We constructed separate linear mixed models to examine the cross-sectional associations of 5 plasma ADRD and aging-related biomarkers with 4 measures of mobility in a cohort of 192 cognitively unimpaired older adults. We secondarily described the association of the same biomarkers with 4 cognitive domain scores. RESULTS Higher phorphorylated-tau181 was associated with worse performance on the expanded short physical performance battery (eSPPB), slower 4m gait speed, and shorter balance time. Higher neurofilament light (NfL) was associated with worse eSPPB, slower 4m gait speed and slower 400m gait speed in adjusted models. However, there was no association of Aβ42/Aβ40, p-tau217, or glial fibrillary acidic protein with mobility. Only p-tau217 was associated with global and processing speed cognitive domain scores in multivariable models, but not after adjusting for multiple comparisons. CONCLUSIONS These data suggest that p-tau181 and NfL are potential markers of mobility performance in cognitively normal older adults, even when they are not associated with cognitive performance. Future studies should examine how such markers predict change over time in mobility and cognitive function and whether they may indicate pathways that could be targeted for preventive management.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The age-dependent influence of the infrapatellar fat pad on chondrocyte extracellular matrix production.","authors":"Ella D'Amico,Tyler J McNeill,Adam M Khay,Gabrielle Gilmer,Kai Wang,Juliana Bergmann,Amrita Sahu,Hirotaka Iijima,Fabrisia Ambrosio","doi":"10.1093/gerona/glaf072","DOIUrl":"https://doi.org/10.1093/gerona/glaf072","url":null,"abstract":"Despite the growing burden of knee osteoarthritis (KOA) on aging populations, our mechanistic understanding of this disease remains lacking. Though KOA is a whole joint disease, the impact of intra-articular structures, like the infrapatellar fat pad (IFP), on cartilage health is unclear. This study investigated the effect of age on paracrine communication between IFPs and chondrocytes. To isolate the effects of the IFP secretome on chondrocytes, aged chondrocytes from male and female mice were incubated with conditioned media from sex-matched young IFPs, aged IFPs, or control media. ECM protein expression increased in both male and female chondrocytes exposed to young, but not aged, conditioned media relative to control media. The effect of the young IFP was not concomitant with changes in ECM degradation proteins, ADAMTS4 or MMP13. To identify factors mediating the effects of the IFP on chondrocytes that are altered with aging, we performed mass spectrometry of young and aged conditioned media and transcriptomics of aged chondrocytes treated with this media. We then integrated the two datasets using network analyses. From the conditioned media, two secreted proteins, Mfge8 and Apoa4, were significantly changed with aging. In silico perturbation of the corresponding receptors of these IFP-secreted factors identified multiple enriched pathways, including negative regulation of nitric oxide synthase activity, in chondrocytes. Overall, the data suggest that young IFPs release paracrine factors that promote ECM production in chondrocytes, potentially via regulation of nitric oxide levels, but that this effect is diminished with aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Long COVID diagnoses in 3.6 million US Medicare beneficiaries with COVID-19.","authors":"Yasin Abul,Daniel A Harris,Preeti Chachlani,Kaleen N Hayes,Andrew R Zullo,Vincent Mor,Stefan Gravenstein","doi":"10.1093/gerona/glaf108","DOIUrl":"https://doi.org/10.1093/gerona/glaf108","url":null,"abstract":"BACKGROUNDLong COVID incidence and risk factors in older adults need to be better characterized to identify risk mitigation strategies. Our aim was to quantify the incidence of Long COVID in a population-based sample of older adults and to describe the association between COVID-19 vaccination and Long COVID risk.METHODSThis cohort study included Medicare fee-for-service beneficiaries ≥ 66 years diagnosed with COVID-19 between October 1, 2021, and March 31, 2023 (index date). Long COVID diagnoses were identified from Medicare Part A-B claims based on ICD-10-CM code U09.9. We measured the number of COVID-19 vaccine doses administered prior to the index date using Medicare Part B claims and pharmacy records. Kaplan-Meier estimators, Cox proportional hazards, and Fine-Grey regression models were used to estimate the 1-year cumulative incidence and relative rate of Long COVID.RESULTSWe identified 3,588,671 Medicare beneficiaries diagnosed with COVID-19. Overall, 3.89% of beneficiaries were diagnosed with Long COVID over one year. A gradient in the one-year cumulative incidence of Long COVID was observed according to the number of prior COVID-19 vaccine doses. Beneficiaries with four or more COVID-19 vaccine doses had a 39% lower adjusted rate of Long COVID relative to beneficiaries without a prior dose (aHR=0.61, 95%CI=0.60-0.62).CONCLUSIONSLong COVID diagnoses in Medicare claims were common in a large sample of older adults with COVID-19, and we observed a gradient in Long COVID risk across the number of prior COVID-19 vaccine doses. Promoting continued vaccination may be an effective strategy to mitigate the burden of Long COVID in older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between biological aging and volunteering engagement in predicting cognitive performance: Evidence from the Harmonized Cognitive Assessment Protocol study","authors":"Seoyoun Kim, Xi Pan","doi":"10.1093/gerona/glaf097","DOIUrl":"https://doi.org/10.1093/gerona/glaf097","url":null,"abstract":"Background Promoting cognitive health and preventing deficits is crucial for improving the population level health and reducing economic burdens. Biological aging, influenced by DNA methylation (DNAm), plays a key role in predicting cognitive performance and brain aging. A more recent body of literature shows that social engagement, and volunteering in particular, may play an important role in modifying the relationship between epigenetic age acceleration and cognitive performance. Methods Using the Harmonized Cognitive Assessment Protocol in the Health and Retirement Study, the current project tests the association between five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPoAm) and cognitive performance. It also examines whether the relationship between epigenetic clocks and cognitive performance differs by volunteering frequency (i.e., effect modification). Results Any level of volunteering was associated with better cognitive performance when compared to no volunteering. All DNAm clocks were associated with cognitive performance, except for PhenoAge. Evidence of effect modification was present for Horvath, PhenoAge, GrimAge, and DunedinPoAm. For PhenoAge and GrimAge, 1-100 hours of volunteering per year mitigated the influenced of accelerated biological age on cognitive performance. For Horvath and DunedinPoAm, the links between epigenetic age acceleration and cognitive performance were less steep for highly engaged volunteers (101+ hours per year). Conclusions The findings underscore the cognitive benefits of engagement in volunteer activities. They further elucidate the interplay between volunteering frequency and epigenetic aging on cognitive performance. The relationship between epigenetic age and cognitive performance also varies based on the level of volunteering engagement.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of oxidative and mitochondrial stress are associated with accelerated pace of aging at midlife in a birth cohort.","authors":"Te-Rina J King-Hudson,Andree G Pearson,Caitlin Dunstan-Harrison,Mathew T Powell,Nicholas J Magon,Teagan S Edwards,Louise N Paton,Jeffry S Tang,Anthony J Kettle,John F Pearson,Jesse Kokaua,Hayley Guiney,Reremoana Theodore,Sandhya Ramrakha,Richie Poulton,Terrie E Moffitt,Elizabeth C Ledgerwood,Mark B Hampton","doi":"10.1093/gerona/glaf105","DOIUrl":"https://doi.org/10.1093/gerona/glaf105","url":null,"abstract":"Oxidative stress and mitochondrial dysfunction are proposed to play prominent roles in the biology of aging. Human studies are limited and confounded by metabolic disturbances associated with age-related diseases. In this study we have measured biomarkers of oxidative and mitochondrial stress in blood samples from up to 864 participants in the longitudinal Dunedin Multidisciplinary Health and Development Study at age 45. We then determined the correlation between these cross-sectional biomarkers and the longitudinal Pace of Aging, a composite score that represents whole-organism functional decline in each participant from 26 to 45 years old, and facial age at 45 years old. Protein carbonyls and allantoin were selected as biomarkers for oxidative stress, and GDF-15 as a marker of mitochondrial stress. Mid-life levels of these biomarkers were low but varied across the population. GDF-15 showed the strongest associations with the Pace of Aging (β = 0.26, p < 0.0001) and facial age (β = 0.12, p =0.001) in sex and smoking adjusted models. The Pace of Aging was also significantly associated with allantoin (β = 0.14, p < 0.0001) and protein carbonyls (β = 0.09, p = 0.005), and allantoin was also associated with facial age (β = 0.08, p = 0.02). These associations remained when the limited number of participants with age-related disease were removed from the analyses. Our results provide evidence of increased oxidative stress and mitochondrial stress in faster aging humans at midlife, well before the onset of age-related disease.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}