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

{"title":"Comparison between the effect of mid-late-life high-intensity interval training and continuous moderate-intensity training in old mouse hearts","authors":"Qiaowei Li, Qin Liu, Zhong Lin, Wenwen Lin, Zhonghua Lin, Feng Huang, Pengli Zhu","doi":"10.1093/gerona/glaf025","DOIUrl":"https://doi.org/10.1093/gerona/glaf025","url":null,"abstract":"The impact of mid-late-life exercise on the aging heart remains unclear, particularly the effects of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMIT). This study was the first to examine cardiac function, tissue characteristics, electrical remodeling, mitochondrial morphology and homeostasis in old mice subjected to CMIT or HIIT, compared to untrained controls. Our results showed that 8-week HIIT significantly improved the survival rate of old mice. HIIT presented advantages on cardiac function, deposition of collagen fibers, neovascularization, aging biomarkers and mitochondrial homeostasis. Only CMIT alleviated age-related cardiac hypertrophy. However, CMIT potentially exacerbated adverse cardiac electrical remodeling. Those findings suggested HIIT as a particularly appealing option for clinical application for aging populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385473","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":"Obesity, sarcopenia, sarcopenic obesity and hypertension: mediating role of inflammation and insulin resistance","authors":"Yuanlin Zou, Hua Ye, Ziqing Xu, Qian Yang, Jicun Zhu, Tiandong Li, Yifan Cheng, Yongjian Zhu, Junxi Zhang, Yacong Bo, Peng Wang","doi":"10.1093/gerona/glae284","DOIUrl":"https://doi.org/10.1093/gerona/glae284","url":null,"abstract":"Background This study aimed to assess the association between obesity, sarcopenia, and sarcopenic obesity with hypertension and to explore the potential mediation of inflammation indicators and insulin resistance. Methods Data from the UK Biobank, a large-scale prospective cohort, were utilized. Obesity was defined using percentage of fat mass, while sarcopenia was defined as low muscle mass and low muscle strength. The primary outcome assessed was new-onset hypertension within a 5-year follow-up period. The association analysis was examined using a Cox regression model. Results A total of 183,091 participants were enrolled in this study. During 5 years of follow-up, 3812 (2.08%) developed hypertension. In the fully adjusted model, compared to men without these conditions, those with obesity, sarcopenia, and sarcopenic obesity had 2.32 times (95% CI, 2.12-2.55), 3.10 times (95% CI, 2.35-4.08), and 3.66 times (95% CI, 2.98-4.50) higher risks of developing hypertension, respectively. Women with obesity, sarcopenia, and sarcopenic obesity had 2.27 times (95% CI, 2.03-2.54), 2.93 times (95% CI, 1.95-4.39), and 4.04 times (95% CI, 3.32-4.91) higher risks of hypertension, respectively. Significant mediating effects of C-reactive protein, neutrophils, white blood cells, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were found, with mediations ranging from 6% to 13% for men and 2% to 21% for women in the association between sarcopenic obesity and hypertension. Conclusions Obesity, sarcopenia, and sarcopenic obesity significantly increased the risk of hypertension. Inflammation and insulin resistance appeared to mediate the association between sarcopenic obesity and hypertension.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258738","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 motoric cognitive risk syndrome and high C-reactive protein serum levels with incident major neurocognitive disorder: Results from the Quebec NuAge cohort","authors":"Olivier Beauchet, Kevin Galéry, Pierrette Gaudreau, Gilles Allali","doi":"10.1093/gerona/glae260","DOIUrl":"https://doi.org/10.1093/gerona/glae260","url":null,"abstract":"Both motoric cognitive risk syndrome (MCR) and C-reactive protein (CRP) serum levels have been separately associated with increased risk of incident major neurocognitive disorder. The study aims to compare the CRP serum levels of older adults with and without MCR, and to examine the associations of MCR, CRP serum levels and their combination with incident major neurocognitive disorder. 915 individuals participating in an older adults population-based observational cohort study with a 3-year follow-up design, were selected. MCR and CRP serum levels were collected at baseline. Incident major neurocognitive disorder was measured at annual follow-up visits using the modified mini-mental state (≤79/100) and simplified instrumental activity daily living scale (<4/4) score values. The prevalence of MCR at baseline assessment was 3.7%. The overall incidence of major neurocognitive disorder was 3.0%. MCR alone (Hazard Ratio (HR)=28.09 with 95% Confidence Interval (CI=[7.00;112.72] and P≤0.001) and MCR with a high CRP serum level (HR=6.33, with 95% CI[1.45;27.62] and P=0.014) were significantly associated with incident major neurocognitive disorder. MCR is a significant risk factor for predicting major neurocognitive disorder in older adults, while serum CRP levels are not. In addition, serum CRP levels reduce the predictive strength of MCR for major neurocognitive disorder.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258594","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":"Engagement of Older Adults in the Design, Implementation and Evaluation of Artificial Intelligence Systems for Aging: A Scoping Review","authors":"Hannah Cho, Oonjee Oh, Nancy Greene, Larissa Gordon, Sherry Morgan, Lisa Walke, George Demiris","doi":"10.1093/gerona/glaf024","DOIUrl":"https://doi.org/10.1093/gerona/glaf024","url":null,"abstract":"Integration of artificial intelligence (AI) in health and healthcare, especially for older adults, has significantly advanced healthcare delivery. AI technologies, with capabilities such as self-learning and pattern recognition, are employed to address social isolation and monitor older adults' daily activities. However, rapid AI development often fails to consider the heterogeneous needs of older populations, which could exacerbate an existing digital divide and inequality. This scoping review examines older adults’ involvement in AI system design, implementation, and evaluation of AI systems in health and healthcare literature, emphasizing the necessity of their input for beneficial AI systems. We conducted a scoping review according to PRISMA-SCR. We reviewed 17 studies, finding that half of these studies (n = 8) engaged older adults during the design phase, a small number (n = 3) during the evaluation stage, and even fewer (n = 2) involved older adults in the implementation stage. Despite AI’s growing role, design processes often overlook older adults’ needs. Our findings emphasize the need for inclusive, participatory design approaches to address ethical and equity challenges, enhancing user engagement and relevance. We also highlight how these approaches address the needs of older adults and improve outcomes. Specifically, we integrated evidence showing the practical benefits of these approaches for better accessibility, usability, and engagement among older adults. While AI has potential to improve healthcare delivery, these approaches must be part of broader efforts to ensure ethical, inclusive, and equitable AI practices, especially in gerontology.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"136 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192040","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 association of physical function and physical performance with DNA methylation clocks in oldest-old living in Singapore - the SG90 cohort","authors":"Jianhua Tay, Weilan Wang, Lihuan Guan, Rajkumar Dorajoo, Lei Feng, Brian K Kennedy, Yap Seng Chong, Tze Pin Ng, Woon-Puay Koh, Andrea B Maier","doi":"10.1093/gerona/glaf022","DOIUrl":"https://doi.org/10.1093/gerona/glaf022","url":null,"abstract":"Deoxyribonucleic acid (DNA) methylation (DNAm) clocks estimate biological age according to DNA methylation. This study investigated the associations between measures of physical function and physical performance and ten DNAm clocks in the oldest-old in Singapore. The SG90 cohort included a subset of community-dwelling oldest-old from the Singapore Chinese Health Study (SCHS) and Singapore Longitudinal Ageing Study (SLAS). Physical function and performance were assessed using Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living (IADL), World Health Organization Disability Assessment Schedule (WHODAS), Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), handgrip strength, normal gait speed, SPPB fast gait speed (FGS), and. DNAm age from peripheral blood mononuclear cells (PBMC) was measured using 18 DNAm clocks, including first generation clocks (PCHorvath1, PCHorvath2, PCHannum, AltumAge, ENCen100+, ENCEN40+, IntrinClock, RetroAgev1 and RetroAgev2) second and third generation clocks (PCPhenoAge, PCGrimAge, GrimAge2, ZhangMRscore, DNAmFitAge and DunedinPACE) and causality-enriched clocks (YingCausAge, YingAdaptAge, YingDamAge). Linear regression was used to analyse associations. The 433 oldest-old individuals had a median age of 88.6 years [87.5; 90.4] and were predominantly Chinese (95.6%) and female (60.3%). Better performance in IADL, WHODAS, SPPB, SPPB FGS and balance were associated with lower GrimAge2 after adjustment for age, sex, and smoking status (pAdj<0.05). GrimAge2 outperformed other DNAm clocks after adjustment for DNAm smoking-pack-years and DNAm-based cell compositions. Better physical function and physical performance were associated with lower DNAm age deviation and pace of ageing. Longitudinal and intervention studies are needed to explore biological mechanisms underlying these observed associations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049739","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 Influence of Sex, Fitness, BMI, and Cardiovascular Risk Factors on Cerebral Blood Velocity Responsiveness to Graded Exercise Testing in Middle-Aged Adults","authors":"Miguel Muñoz-Muñoz, Max Weston, Miguel Sierra-Ramón, Bert Bond, Javier Leal-Martín, Owen W Tomlinson, Iván Baltasar-Fernández, María M Morín-Martín, José Losa-Reyna, Julian Alcazar, Francisco José García-García, Ignacio Ara","doi":"10.1093/gerona/glae257","DOIUrl":"https://doi.org/10.1093/gerona/glae257","url":null,"abstract":"Mean middle cerebral artery velocity (MCAv) and the pulsatility index (PI), at rest and in response to exercise, are important markers of cerebrovascular health status in middle-aged adults, when vascular decline assumes substantial relevance. Thus, this study aimed to describe and compare the responses of MCAv and PI to incremental exercise. Two hundred and forty-eight volunteers (50–58 years, 55% women) completed a ramp test on a cycle-ergometer. Gas exchange was assessed on a breath-by-breath basis. MCAv was measured via transcranial Doppler and PI calculated. Cardiovascular disease risk (CVR) factors were determined and comprised of measurements of central obesity, blood pressure, fasted plasma glucose, and lipids. The MCAv and PI responses to exercise were compared across body mass index categories, CVR score, and fitness status. We found sex-specific differences in MCAv and PI at rest. However, both sexes showed a similar relative change to baseline (Δ%MCAvmean). Regarding body mass index, obese women (body mass index > 30 kg m−2) had lower MCAv and Δ%MCAvmean and higher PI compared with normo-weight women during exercise. Apart, women with a 0 CVR score showed higher MCAv and lower PI during exercise than those with a score of +3 CVR. Differences between low and high CVR during exercise in Δ%MCAvmean were also found. Eventually, low fitness showed diminished MCAv and a lower response to exercise than high fitness. This study has highlighted significant variability in MCAv responsiveness to exercise among middle-aged adults. Body composition, CVR, and fitness status may play a significant role in preserving cerebrovascular health. These findings shed light on the importance of understanding the cerebrovascular response to exercise.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992572","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":"Identification of association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization and colocalization analyses","authors":"Jiale Xie, Jinrong Hao, Xin Xu, Jiachen Wang, Dinglong Yang, Hui Yu, Junfei Guo, Mingyi Yang, Peng Xu","doi":"10.1093/gerona/glaf006","DOIUrl":"https://doi.org/10.1093/gerona/glaf006","url":null,"abstract":"Background Mitochondrial dysfunction has been demonstrated to be an important hallmark of sarcopenia, yet its specific mechanism remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data for sarcopenia-related traits were used as outcomes to examine their genetic association. Methods A total of 1,136 mitochondrial-related genes from the human MitoCarta3.0 database were extracted. Genetic instruments for them were obtained from gene expression quantitative trait locus (eQTLs) study (n = 31,684). Aggregated data for sarcopenia-related traits [(including low hand grip strength (LHGS), appendiceal lean mass (ALM), and usual walking pace (UWP) were provided by large-scale genome-wide association studies (GWASs). We integrated eQTLs data with GWAS data to estimate genetic association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization (SMR) analysis. Additionally, we implemented colocalization analysis to strengthen their association. Finally, eQTLs data from skeletomuscular tissue (n = 706) was used to validate the primary findings. Results By integrating the analysis results from the three sarcopenia-related traits, two mitochondrial genes genetically associated with sarcopenia were identified, namely UQCC1 (tier 2 evidence) and ETFDH (tier 3 evidence). Specifically, elevated expression levels of UQCC1 increased LHGS risk (OR = 1.114; 95% CI, 1.078–1.152; P-FDR = 1.70 × 10-7), which matched the negative association between it and UWP (Beta = -0.015; 95% CI, -0.021 – -0.010; P-FDR = 6.70 × 10-5). Furthermore, elevated expression levels of ETFDH were found to be associated with both lower ALM (Beta = 0.031; 95% CI, 0.020–0.042; P-FDR = 1.41 × 10-6) and UWP (Beta = 0.013; 95% CI, 0.006–0.021; P-FDR = 0.029). Of note, consistent results were replicated in specific skeletomuscular tissues, further suggesting our findings were robust. Conclusions Our analyses revealed the genetic association between two mitochondrial-related genes, i.e., UQCC1 and ETFDH, and sarcopenia, highlighting the pivotal role of mitochondrial dysfunction driven by these genes in the pathogenesis of sarcopenia. Importantly, these candidate genes represent potential clinical drug targets for the treatment of sarcopenia.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988536","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":"Nicotinamide Prevents The Plasticity Impairments And The Cognitive Dysfunction Caused By Bone Fracture In Older Mice","authors":"Tatiana Guncay, Jorge Concha, Pedro Lobos, Jamileth More, Barbara Bruna, Daniel Sansores, Pamela Contreras, Daniela P Ponce, Julian Brañez, Gabriel Quiroz, Genaro Barrientos, Cecilia Hidalgo, Felipe Salech","doi":"10.1093/gerona/glae303","DOIUrl":"https://doi.org/10.1093/gerona/glae303","url":null,"abstract":"Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with Nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery. Female C57BL/6J mice aged 20-22 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze). Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1 beta mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and BDNF protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1 beta and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988539","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":"Incomplete Ascertainment of Mortality in a Nationally Representative Longitudinal Study of Community-Living Older Americans","authors":"Thomas M Gill, Jingchen Liang, Brent Vander Wyk, Linda Leo-Summers, Yi Wang, Robert D Becher, Kendra Davis-Plourde","doi":"10.1093/gerona/glaf014","DOIUrl":"https://doi.org/10.1093/gerona/glaf014","url":null,"abstract":"Background In longitudinal studies of older persons, complete ascertainment of mortality is needed to minimize potential biases. To ascertain mortality in the National Health and Aging Trends Study (NHATS), investigators are advised to use its Sensitive files, which include month and year of death on most decedents who had not dropped out of the study. Because losses to follow-up are not insubstantial, ascertainment of mortality is likely incomplete. Methods We used linked Medicare data as the reference standard to determine the extent by which mortality is underestimated in NHATS through use of its recommended strategy. Ascertainment of mortality was compared between the two strategies over 10 years for 7,608 members of the 2011 cohort and 5 years for 7,498 members of the 2015 cohort. Results The Sensitive files did not identify a large number of decedents, leading to suboptimal sensitivity, ranging from 61.3% (2011 cohort, 10 years) to 75.5% (2015 cohort, 5 years). Some non-decedents were also misclassified as dead using the Sensitive files. Cumulative mortality rates were modestly lower for the recommended strategy, although the number of participants at risk decreased markedly over time. Mortality incidence rates were also modestly lower for the recommended strategy, with incidence rate ratios ranging from 0.88 (2011 cohort, 10 years) to 0.94 (2011 cohort, 5 years). Conclusions The strategy recommended by NHATS leads to incomplete ascertainment and, to a lesser degree, misclassification of mortality. Caution may be warranted when interpreting results of longitudinal analyses in NHATS that evaluate mortality using the recommended strategy.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988537","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":"Robust metabolomic age prediction based on a wide selection of metabolites","authors":"Tariq Faquih, Astrid van Hylckama Vlieg, Praveen Surendran, Adam S Butterworth, Ruifang Li-Gao, Renée de Mutsert, Frits R Rosendaal, Raymond Noordam, Diana van Heemst, Ko Willems van Dijk, Dennis O Mook-Kanamori","doi":"10.1093/gerona/glae280","DOIUrl":"https://doi.org/10.1093/gerona/glae280","url":null,"abstract":"Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. the difference between the chronological age and biologically driven aging could be more informative in reflecting health status. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (678 endogenous and 148 xenobiotics) measured by an untargeted platform in relatively healthy blood donors aged 18-75 years from the INTERVAL study (N=11,977;50.2% men). After bootstrapping internal validation, the metabolomic age prediction models demonstrated high performance with an adjusted R2 of 0.83 using all metabolites and 0.82 using only endogenous metabolites. The former was significantly associated with obesity and cardiovascular disease (CVD) in the NEO study (N=599;47.0% men; age range=45-65) due to the contribution of medication derived metabolites—namely salicylate and ibuprofen—and environmental exposures such as cotinine. Additional metabolomic age prediction models using all metabolites were developed for men and women separately. The models had high performance (R²=0.85 and 0.86) but shared a moderate correlation of 0.72. Furthermore, we observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, and androgenic and progesterone-related metabolites. Our strongest predictors across all models were novel and included hydroxyasparagine (Model Endo+Xeno β=4.74), vanillylmandelate (β=4.07), and 5,6-dihydrouridine (β=-4.2). Our study presents a robust metabolomic age model that reveals distinct sex-based age-related metabolic patterns and illustrates the value of including xenobiotic to enhance metabolomic prediction accuracy.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987532","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}