GeroScience最新文献

{"title":"Association of longitudinal body mass index trajectories with phenotypic age acceleration: a cross-sectional study based on growth mixture modeling","authors":"Yalan Liu, Li Zhang, Zhaofeng Jin, Lin Zhang, Yan Song, Li He","doi":"10.1007/s11357-025-01681-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01681-y","url":null,"abstract":"<p>To examine the association between body mass index (BMI) trajectories, early and recent BMI changes, and phenotypic age acceleration (PhenoAgeAccel), addressing inconsistent findings in previous studies on weight change and aging. Data from the National Health and Nutrition Examination Survey from 2005 to 2018 were used, selecting participants aged 50 years and older. A growth mixture model was employed to identify BMI trajectories. The association between different BMI trajectories and PhenoAgeAccel was assessed using linear and multinomial logistic regression models. The nonlinear effects of BMI changes were identified through threshold effect analysis. Among 5404 participants, the four BMI trajectories identified were as follows: stable weight (29.07%), midlife weight gain (24.31%), late-life weight gain (32.22%), and chronic obesity (14.41%). The chronic obesity group exhibited the most significant elevations in PhenoAgeAccel, indicating they were phenotypically older compared to other groups (<i>β</i> = 4.34, 95% confidence interval 3.67–5.02). Early BMI changes of less than 6% were associated with being phenotypically younger (<i>β</i> = − 5.06, <i>P</i> = 0.029), whereas increases exceeding 6% were linked to being phenotypically older (<i>β</i> = 2.83, <i>P</i> &lt; 0.001). The key threshold for recent BMI changes was 2%; changes below this level were associated with being phenotypically younger, while those exceeding this threshold were linked to being phenotypically older (<i>P</i> &lt; 0.001). This cross-sectional study suggests that individuals with long-term chronic obesity tend to be phenotypically older, whereas those with stable body weight are more likely to be phenotypically younger.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"275 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of enhanced glycolysis on cardiac aging","authors":"Anna Faakye, Kylene M. Harold, Satoshi Matsuzaki, Atul Pranay, Maria F. Mendez Garcia, Brooke L. Loveland, Sandra N. Rigsby, Frederick F. Peelor, Craig Eyster, Benjamin F. Miller, Timothy M. Griffin, Michael Kinter, Ying Ann Chiao, Kenneth M. Humphries","doi":"10.1007/s11357-025-01656-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01656-z","url":null,"abstract":"<p>Cardiac aging is associated with metabolic changes, including an increased reliance on glycolysis, and an increased susceptibility to cardiovascular diseases. This study explores the relationship between enhanced cardiac glycolysis and aging using the Glyco^Hi mouse model, characterized by constitutively elevated glycolysis. We compared cardiac function, metabolism, mitochondrial performance, and hallmarks of aging between aged (21 and 24 months) Glyco^Hi and wild-type (WT) mice across sexes. Our findings reveal modest reductions in cardiac function in aged Glyco^Hi mice compared to WT mice, with sex-specific differences in heart size and collagen concentration. Female Glyco^Hi hearts exhibited hypertrophy without fibrosis, while males showed elevated collagen levels. Whole-body metabolic assessments revealed similar energy expenditure and respiratory patterns across genotypes, with females displaying less circadian-associated variation in metabolism. Mitochondrial analyses showed that aged Glyco^Hi hearts maintained metabolic adaptations favoring glycolysis but did not exhibit significant bioenergetic dysfunction or oxidative stress. Pyruvate dehydrogenase activity, initially elevated in younger Glyco^Hi hearts, normalized to WT levels with age. Proteomic and metabolomic analyses highlighted distinct profiles between genotypes, with Glyco^Hi hearts exhibiting increased glycolytic enzyme levels and reduced abundance of fatty acid oxidation proteins. Despite these differences, indicators of oxidative stress, proteostasis, and cellular senescence were comparable between genotypes, suggesting no acceleration of aging-related dysfunction. This study demonstrates that increased cardiac glycolysis alone does not suffice to drive accelerated cardiac aging. Instead, metabolic and functional changes in aged Glyco^Hi hearts reflect adaptations rather than pathological declines, providing insights into potential metabolic targets for interventions against cardiac aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"12 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The road to a long lifespan in the Persian squirrel, a natural model for extended longevity: resisting free radical stress and healthy phospholipids","authors":"Fahimeh Salehi, Gholamreza Kavoosi, Paul. J. Jacobs, Nigel C. Bennett, Shahin Ahmadian, Babak Bastani, Mahdi Gholami","doi":"10.1007/s11357-025-01668-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01668-9","url":null,"abstract":"<p>Longevity is influenced by various factors, including fatty acid composition and free radical stress, which relate to the membrane pacemaker and rate of living hypotheses. While these aspects are well-documented in some long-lived species, they remain largely unexplored in tree squirrels. This study aimed to compare oxidative stress, antioxidant activity, nitrosative stress, and lipid composition between the long-lived Persian squirrel (<i>Sciurus anomalus</i>) and the short-lived Wistar rat across age cohorts (younger and older). Tissue homogenates from skin, liver, skeletal muscle, spleen, lung, and kidney were analysed for lipid composition (monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), arachidonic to linoleic acid ratio, peroxidation index, and unsaturation index. Oxidative, nitrosative, and antioxidant markers were assessed, including NADPH oxidase, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase (GST), nitric oxide synthase, superoxide, hydrogen peroxide, nitric oxide, malondialdehyde, 4-hydroxynonenal, and total antioxidant capacity (TAC). Squirrels demonstrated higher GST activity, lower free radical stress, lower PUFA, and higher MUFA compared to rats. Antioxidant activities, except for TAC were negatively correlated with longevity. Older squirrels exhibited similar oxidative, nitrosative, and antioxidant profiles to younger squirrels, whereas younger rats displayed highly susceptible fatty acids, similar to older rats. The Persian squirrel’s longevity appears closely linked to fatty acid composition and free radical resistance, likely due to increased GST activity. We propose GST’s multifunctional role in reducing inflammation, enhancing immune response, providing disease resistance, and antioxidant activity contributes significantly to the longevity of the Persian squirrel.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"12 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond genes and environment: mapping biological stochasticity in aging","authors":"Adam J. Hruby, Gilberto Garcia, Max A. Thorwald, Caleb E. Finch, Joshua Johnson, Ryo Higuchi-Sanabria","doi":"10.1007/s11357-025-01673-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01673-y","url":null,"abstract":"<p>Aging is characterized by extensive variability in the onset of morbidity and mortality, even in genetically identical populations with carefully controlled environments. This points to the important role stochasticity plays in shaping the divergent aging process between individual organisms. Here, we survey how stochastic factors at the level of molecules, cells, tissues, and organisms manifest in and impact the aging process, with a focus on the nematode <i>Caenorhabditis elegans</i>. Findings of stochasticity in <i>C. elegans</i> give additional insights for aspects of aging in the more complex settings of mammals with parallels drawn between organisms when appropriate. The emerging understanding of the stochastic contributors to longevity will enhance research strategies and medical interventions for personalized medicine.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"273 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of cardiorespiratory fitness with brain white matter microstructural integrity and white matter hyperintensity volume across the adult lifespan","authors":"Junyeon Won, Takashi Tarumi, Tsubasa Tomoto, Kevin Shan, Karen M. Rodrigue, Kristen M. Kennedy, Denise C. Park, Rong Zhang","doi":"10.1007/s11357-025-01664-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01664-z","url":null,"abstract":"<p>Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O_2peak) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We hypothesized that higher CRF is associated with less deterioration in WM microstructural integrity and WMH across the adult lifespan, which in turn is associated with better cognitive performance. A total of 177 healthy adults underwent treadmill exercise testing to measure V̇O_2peak, MRI scan to measure free water (FW)–corrected DTI metrics and whole-brain WMH volume, and a comprehensive cognitive test battery. Linear regression models were used to examine the associations of DTI metrics and WMH volume with age, V̇O_2peak, and age × V̇O_2peak interaction. Higher CRF was associated with lower FW. Age × V̇O_2peak interactions were observed in FW of the corpus callosum (CC) and WMH volume, such that the positive regression slopes of FW and WMH volume with age were lower in those with higher V̇O_2peak than those with lower V̇O_2peak. Lower WMH volume and FW in the CC were associated with better fluid cognition composite score. In conclusion, higher CRF is associated with less deteriorations in brain WM integrity and better cognitive function across the adult lifespan. These findings highlight the importance of maintaining and improving CRF to slow brain aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"35 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological age acceleration and interaction with genetic predisposition in the risk of type 2 diabetes and coronary artery disease","authors":"Guangrui Yang, Xihao Du, Xuanwei Jiang, Jingxuan Wang, Shuxiao Shi, Victor W. Zhong","doi":"10.1007/s11357-025-01671-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01671-0","url":null,"abstract":"<p>Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status. In this prospective UK Biobank study, BA acceleration was measured using the Klemera-Doubal method BA (KDM-BA) and Phenotypic age (PhenoAge). Cox models estimated associations of BA acceleration with incident T2D (<i>n</i> = 271,885) and CAD (<i>n</i> = 270,054). Both additive and multiplicative interactions between BA acceleration and polygenic risk score (PRS) were examined. Predictive performance was assessed by adding BA, PRS, and their interactions to traditional risk models. BA acceleration was positively associated with incident T2D (HR_{Q4 vs Q1} for KDM-BA: 2.38 [95% CI, 2.22–2.56]; HR_{Q4 vs Q1} for PhenoAge: 1.85 [95% CI, 1.72–1.99]) and CAD (HR_{Q4 vs Q1} for KDM-BA: 1.67 [95% CI, 1.58–1.76]; HR_{Q4 vs Q1} for PhenoAge: 1.33 [95% CI, 1.27–1.39]). Significant multiplicative interactions were observed between BA acceleration and PRS (all <i>P</i> for multiplicative interaction ≤ 0.002). Individuals with highest BA acceleration and PRS had strongest risk elevation for T2D (HR for KDM-BA, 6.89 [95% CI, 6.03–7.87]; HR for PhenoAge, 6.28 [95% CI, 5.28–7.46]) and CAD (HR for KDM-BA, 2.80 [95% CI, 2.59–3.02]; HR for PhenoAge, 2.25 [95% CI, 2.07–2.45]). Additive interactions were observed for T2D with 18–28% of risk attributable to BA-genetic interaction. Adding BA measures and PRS to traditional risk models significantly improved prediction for both diseases (Δ <i>C</i>-statistic 0.024–0.034). In conclusion, BA acceleration was positively associated with incident T2D and CAD, especially in individuals with high genetic predisposition, and improved T2D and CAD prediction beyond traditional risk factors.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic clocks and inflammaging: pitfalls caused by ignoring cell-type heterogeneity","authors":"Xiaolong Guo, Andrew E. Teschendorff","doi":"10.1007/s11357-025-01677-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01677-8","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"91 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global and tissue-specific transcriptomic dysregulation in human aging: Pathways and predictive biomarkers","authors":"Muhammad Arif, Andrea Lehoczki, György Haskó, Falk W. Lohoff, Zoltan Ungvari, Pal Pacher","doi":"10.1007/s11357-025-01672-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01672-z","url":null,"abstract":"<p>Aging is a universal biological process that impacts all tissues, leading to functional decline and increased susceptibility to age-related diseases, particularly cardiometabolic disorders. While aging is characterized by hallmarks such as mitochondrial dysfunction, chronic inflammation, and dysregulated metabolism, the molecular mechanisms driving these processes remain incompletely understood, particularly in a tissue-specific context. To address this gap, we conducted a comprehensive transcriptomic analysis across 40 human tissues using data from the Genotype-Tissue Expression (GTEx) project, comparing individuals younger than 40 years with those older than 65 years. We identified over 17,000 differentially expressed genes (DEGs) across tissues, with distinct patterns of up- and down-regulation. Enrichment analyses revealed that up-regulated DEGs were associated with inflammation, immune responses, and apoptosis, while down-regulated DEGs were linked to mitochondrial function, oxidative phosphorylation, and metabolic processes. Using gene co-expression network (GCN) analyses, we identified 1,099 genes as dysregulated nodes (DNs) shared across tissues, reflecting global aging-associated transcriptional shifts. Integrating machine learning approaches, we pinpointed key aging biomarkers, including GDF15 and EDA2R, which demonstrated strong predictive power for aging and were particularly relevant in cardiometabolic tissues such as the heart, liver, skeletal muscle, and adipose tissue. These genes were also validated in plasma proteomics studies and exhibited significant correlations with clinical cardiometabolic health indicators. This study provides a multi-tissue, integrative perspective on aging, uncovering both systemic and tissue-specific molecular signatures. Our findings advance understanding of the molecular underpinnings of aging and identify novel biomarkers that may serve as therapeutic targets for promoting healthy aging and mitigating age-related diseases.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"23 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on article: Acquired hemophilia A as a disease of the elderly by Lehoczki A. et al.","authors":"Antonella Mameli,Francesco Marongiu,Doris Barcellona","doi":"10.1007/s11357-025-01663-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01663-0","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"35 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the progression of MCI and Alzheimer’s disease on structural brain integrity and other features with machine learning","authors":"Marthe Mieling, Mushfa Yousuf, Nico Bunzeck","doi":"10.1007/s11357-025-01626-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01626-5","url":null,"abstract":"<p>Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer’s disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, those with mild cognitive impairment (MCI) and AD dementia patients. Features included structural MRI, CSF status, demographics, and genetic data. Analyses comprised one cross-sectional multi-class classification (CN vs. MCI vs. AD dementia, <i>n</i> = 568) and two longitudinal binary-class classifications (CN-to-MCI converters vs. CN stable, <i>n</i> = 92; MCI-to-AD converters vs. MCI stable, <i>n</i> = 378). All classifications achieved 70–77% accuracy and 61–83% precision. Key features were CSF status, hippocampal volume, entorhinal thickness, and amygdala volume, with a clear dissociation: hippocampal properties contributed to the conversion to MCI, while the entorhinal cortex characterized the conversion to AD dementia. The findings highlight explainable, trajectory-specific insights into AD progression.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"67 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}