GeroScience最新文献

{"title":"Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.","authors":"Martina Vinicki, Tea Pribić, Frano Vučković, Azra Frkatović-Hodžić, Isaac Plaza-Andrades, Francisco Tinahones, Joseph Raffaele, José Carlos Fernández-García, Gordan Lauc","doi":"10.1007/s11357-024-01349-z","DOIUrl":"10.1007/s11357-024-01349-z","url":null,"abstract":"<p><p>With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29-45 years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1777-1788"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371598","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":"Novel biomarkers of mitochondrial dysfunction in Long COVID patients.","authors":"Titanilla Szögi, Barbara N Borsos, Dejana Masic, Bence Radics, Zsolt Bella, Andrea Bánfi, Nóra Ördög, Csenge Zsiros, Ágnes Kiricsi, Gabriella Pankotai-Bodó, Ágnes Kovács, Dóra Paróczai, Andrea Lugosi Botkáné, Béla Kajtár, Farkas Sükösd, Andrea Lehoczki, Tamás Polgár, Annamária Letoha, Tibor Pankotai, László Tiszlavicz","doi":"10.1007/s11357-024-01398-4","DOIUrl":"10.1007/s11357-024-01398-4","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30-40% experience persistent symptoms collectively known as Long COVID, post-COVID-19 syndrome, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). These enduring symptoms, including fatigue, respiratory difficulties, body pain, short-term memory loss, concentration issues, and sleep disturbances, can persist for months. According to recent studies, SARS-CoV-2 infection causes prolonged disruptions in mitochondrial function, significantly altering cellular energy metabolism. Our research employed transmission electron microscopy to reveal distinct mitochondrial structural abnormalities in Long COVID patients, notably including significant swelling, disrupted cristae, and an overall irregular morphology, which collectively indicates severe mitochondrial distress. We noted increased levels of superoxide dismutase 1 which signals oxidative stress and elevated autophagy-related 4B cysteine peptidase levels, indicating disruptions in mitophagy. Importantly, our analysis also identified reduced levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in these patients, serving as a novel biomarker for the condition. These findings underscore the crucial role of persistent mitochondrial dysfunction in the pathogenesis of Long COVID. Further exploration of the cellular and molecular mechanisms underlying post-viral mitochondrial dysfunction is critical, particularly to understand the roles of autoimmune reactions and the reactivation of latent viruses in perpetuating these conditions. This comprehensive understanding could pave the way for targeted therapeutic interventions designed to alleviate the chronic impacts of Long COVID. By utilizing circulating ccf-mtDNA and other novel mitochondrial biomarkers, we can enhance our diagnostic capabilities and improve the management of this complex syndrome.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"2245-2261"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567427","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":"Cardiac-specific overexpression of serum response factor regulates age-associated decline in mitochondrial function","authors":"Pankaj Patyal, Gohar Azhar, Xiaomin Zhang, Ambika Verma, Jeanne Y. Wei","doi":"10.1007/s11357-025-01629-2","DOIUrl":"https://doi.org/10.1007/s11357-025-01629-2","url":null,"abstract":"<p>Cardiac aging is an intrinsic process that leads to impaired heart function, along with cellular and molecular changes. Recent research highlights the important role of mitochondria in cardiac function, due to the heart's high energy demands. Serum response factor (SRF), a transcription factor involved in regulating actin and smooth muscle gene expression, is well known as a regulator of various aspects of cardiac function. However, its role in mitochondrial regulation and cardiac aging is poorly understood. Our laboratory generated a transgenic mouse model with cardiac-specific overexpression of SRF, which exhibits characteristics of diastolic dysfunction and accelerated cardiac aging in young adult transgenic mice. In this study, we tested how cardiac-specific overexpression of SRF affects age associated mitochondrial dysfunction in the heart. Our results showed that cardiac specific SRF overexpression reduced the lifespan of mice and induced cardiomyopathy. Histological analysis revealed cardiac hypertrophy and fibrosis in transgenic mice hearts. SRF overexpression led to significant alterations in mitochondrial structure and function, including reduced mitochondrial biogenesis and dysregulation of oxidative phosphorylation. These changes were accompanied by increased oxidative stress, a decline in antioxidant enzyme activity, and disrupted calcium handling. Moreover, cardiac-specific SRF overexpression activated the MAPK signaling pathway. Our findings were further corroborated by similar mitochondrial dysfunction observed in a human cardiomyocyte cells transfected with SRF plasmid. Taken together, these findings suggest that SRF plays a novel role in cardiac aging, thus establishing SRF as a potential therapeutic target for mitigating age-associated decline in mitochondrial function and preserving cardiac health in older adults.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"41 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745538","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 role of purpose in life in healthy aging: implications for the Semmelweis Study and the Semmelweis-EUniWell Workplace Health Promotion Model Program","authors":"Virág Zábó, Andrea Lehoczki, Monika Fekete, Ágnes Szappanos, Péter Varga, Marianna Moizs, Giorgia Giovannetti, Yura Loscalzo, Marco Giannini, M. Cristina Polidori, Beatrix Busse, Miklos Kellermayer, Róza Ádány, György Purebl, Zoltan Ungvari","doi":"10.1007/s11357-025-01625-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01625-6","url":null,"abstract":"<p>The global aging population presents significant challenges to public health systems, particularly in countries like Hungary, which faces some of the least favorable health indicators in the European Union. To address these challenges, Purpose in Life (PIL) has emerged as a critical determinant of healthy aging, influencing physical, mental, and social health. Defined as a sense of meaning, direction, and intentionality, PIL promotes resilience, mitigates age-related decline, and fosters well-being. This review explores the theoretical frameworks, mechanisms, and practical implications of PIL in the context of aging. Biologically, PIL regulates stress responses, contributing to reduced disease risk and improved longevity. Psychologically, PIL fosters resilience, self-regulation, and positive emotions, which buffer against mental health challenges and support cognitive health. Socially, PIL strengthens meaningful relationships, promotes prosocial behaviors, and fosters collective purpose, reducing isolation and enhancing social cohesion. These mechanisms interact to create a synergistic effect that supports healthy aging trajectories. The Semmelweis Study, Hungary’s most extensive workplace cohort study, offers a unique opportunity to integrate PIL assessment into its longitudinal design, providing novel insights into how PIL influences aging outcomes. Complementing this research, the Semmelweis-EUniWell Workplace Health Promotion Program translates these insights into actionable interventions, designed to enhance employee well-being and productivity. Drawing from global best practices, including insights from Blue Zones and Mediterranean-inspired interventions, Hungary can position PIL as a cornerstone of its healthy aging agenda. Incorporating PIL-focused strategies into workplace health programs and national public health policies holds the potential to extend healthspan, reduce healthcare costs, and foster a resilient and purposeful aging population. This review highlights the transformative potential of PIL in addressing the multifaceted challenges of aging and advancing public health goals.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"72 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734072","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":"Uncovering somatic genetic drivers in prostate cancer through comprehensive genome-wide analysis","authors":"Lede Lin, Zhen Li, Kai Chen, Yanxiang Shao, Xiang Li","doi":"10.1007/s11357-025-01623-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01623-8","url":null,"abstract":"<p>Given that hereditary prostate cancer (PCa) accounts for only a small fraction of PCa phenotypes, there is still a substantial journey ahead in exploring the somatic genetic drivers contributing to sporadic PCa. The expression quantitative trait loci (eQTLs) data were sourced from the GTEx dataset for prostate-specific genes, and the summary statistic information was collected for 5854 genes. Genetic associations with PCa were extracted from three well-established consortiums: the UK Biobank (9131 cases and 173,493 controls), the PRACTICAL study (79,148 cases and 61,106 controls), and the FinnGen cohort (13,216 cases and 119,948 controls). To prioritize potential causal targets, additional analysis, including the protein–protein interaction (PPI), The Cancer Genome Atlas (TCGA) dataset, and the single-cell-type expression analysis, was performed. Generally, a total of 150 common significant genes with the same causal association with PCa were identified. Out of the 150 genes examined, 67.33% (101/150) were found to have protein-coding functions, while only 30.67% (46/150) of these genes had prior mentions in the scientific literature. Notably, the analysis of the TCGA dataset showed that only 44.67% (67/150) of the genes produced consistent results with the Mendelian randomization (MR) analysis. Furthermore, the evaluation of single-cell RNA-seq data and colocalization analysis singled out MSMB as a critical gene associated with the occurrence of PCa. We pinpointed a range of prostate-specific genes that display causal associations with the onset of PCa. Among these, the MSMB gene emerged as a pivotal factor linked to PCa, demonstrating robust consistency across all four assessments, including the MR, TCGA dataset, single-cell RNA-seq data, and colocalization analysis. These findings provided fresh perspectives on the pathogenesis of PCa and presented potential targets for drug development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734062","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 construction for prediction of mortality in the Chinese population","authors":"Kaiyue Wang, Jingli Gao, Ying Liu, Zuyun Liu, Yaqi Li, Shuohua Chen, Liang Sun, Shouling Wu, Xiang Gao","doi":"10.1007/s11357-025-01612-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01612-x","url":null,"abstract":"<p>Efforts to increase health span bring to light the necessity of constructing biological age (BA) for measuring aging. However, universally adaptive BA needs further investigation, especially among the Chinese population. Therefore, this study aimed to construct BA using routine clinical markers for the Chinese population. Included were two Chinese prospective cohorts, the Kailuan Study I (<i>n</i> = 83,571) for developing BA and the Kailuan Study II (<i>n</i> = 21,229) for validation. Leveraging baseline age-related clinical markers, we developed phenotypic BA (Pheno-Age) using Levine’s methods and Klemera-Doubal BA (KDM-Age) using KDM methods and calculated the residuals of regressions of the two BA measured at baseline and during follow-up on chronological age, namely BA acceleration. The predictive performance of baseline, cumulative average, and updated BAs on mortality was evaluated using the area under the curve (AUC) and calibration plots. COX regressions were used to estimate hazard rations (HRs) and 95% confidence intervals (CIs) for the BA acceleration and risk of mortality. During 1,443,857 person-years of follow-up, 12,679 deaths were recorded in the two cohorts. Baseline Pheno-Age and KDM-Age produced desirable predictions for mortality in both the Kailuan Study I (AUC, 0.810 and 0.806, respectively) and the Kailuan Study II (AUC, 0.867 and 0.819, respectively). Calibration plots showed reasonable agreement between predicted and observed probabilities. The pooled multivariable-adjusted HRs (95% CIs) for per standard deviation increment of baseline Pheno-Age acceleration and mortality was 1.24 (1.18, 1.30), and for KDM-Age acceleration was 1.16 (1.10, 1.21). Similar predictive performance and association were observed when using cumulative average or updated BA. The associations were stronger in the adults aged ≤60 years, smokers, and drinkers, relative to their counterparts (<i>P</i> for interaction &lt;0.05 for all). Pheno-Age and KDM-Age, developed and validated in the two large prospective cohorts, could predict mortality, independent of chronological age and other potential confounders, in Chinese populations.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"36 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723448","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":"Correction to: Cognitive frailty and functional disability in older adults: A 10‑year prospective cohort study in Japan.","authors":"Sanmei Chen, Tao Chen, Takanori Honda, Hiro Kishimoto, Yu Nofuji, Kenji Narazaki","doi":"10.1007/s11357-025-01618-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01618-5","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729716","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":"Time restricted feeding with or without ketosis influences metabolism-related gene expression in a tissue-specific manner in aged rats","authors":"Sarah Ding, Anisha Banerjee, Sara N. Burke, Abbi R. Hernandez","doi":"10.1007/s11357-025-01632-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01632-7","url":null,"abstract":"<p>Many of the “hallmarks of aging” involve alterations in cellular and organismal metabolism. One pathway with the potential to impact several traditional markers of impaired function with aging is the PI3K/AKT metabolic pathway. Regulation of this pathway includes many aspects of cellular function, including protein synthesis, proliferation, and survival, as well as many downstream targets, including mTOR and FOXOs. Importantly, this pathway is pivotal to the function of every organ system in the human body. Thus, we investigated the expression of several genes along this pathway in multiple organs, including the brain, liver, and skeletal muscle, in aged subjects that had been on different experimental diets to regulate metabolic function since mid-life. Specifically, rats were fed a control ad lib diet (AL), a time restricted feeding diet (cTRF), or a time restricted feeding diet with ketogenic macronutrients (kTRF) for the majority of their adult lives (from 8 to 25 months). We previously reported that regardless of macronutrient ratio, TRF-fed rats in both macronutrient groups required significantly less training to acquire a biconditional association task than their ad lib fed counterparts. The current experiments expand on this work by quantifying metabolism-related gene expression across tissues and interrogating for potential relationships with cognitive performance. Within the brain, SIRT1 and MAPK8 were reduced in CA3 of kTRF-fed rats. Additionally, IGF1 expression was significantly upregulated in the CA1 of cTRF-fed rats, but this effect was ameliorated in the kTRF fed group. AKT and FOXO1 expression were significantly reduced in kTRF-fed rats within liver. Interestingly, AKT expression within the perirhinal cortex (PER) was higher in kTRF rats with the best cognitive performance, and FOXO1 expression was higher in the CA3 of AL-fed rats correlated with the poorest cognitive performance. Together, these data demonstrate diet- and tissue-specific alterations in metabolism-related gene expression and their correlation with cognitive status.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"10 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723395","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":"Association between night shift work and markers of metabolism, cardiovascular and immune system in a population-based German cohort","authors":"Nora Bittner, Horst-Werner Korf, Susanne Moebus, Börge Schmidt, Svenja Caspers","doi":"10.1007/s11357-025-01596-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01596-8","url":null,"abstract":"<p>In humans, night shift work is a major reason for chronodisruption, may affect health and increase the risk of a metabolic syndrome, but results obtained so far are ambiguous. In this population-based, cross-sectional study, PRESENT and FORMER shift workers were compared to age- and sex-matched controls, who never worked in shift with regard to body mass index, waist-hip-ratio total, high-density lipoprotein and low-density lipoprotein, cholesterol and C-reactive protein. Moreover, association with sex, length of shift work and medication were investigated. The present results do not support the hypothesis that night shift work per se is associated to an increased risk of metabolic syndrome, and cardiovascular and immune malfunctions: no differences were found in mean anthropomteric and blood values between present or former shift workers and respective matched controls. When analyzing the proportion of participants showing values beyond the clinically relevant cut-offs, no general effect of shift work was observed, but the data may suggest an interaction between shift work and sex. These divergent results may be due to differences in the socio-economic status, the health care system and the shift schedule. All these parameters need to be considered in future studies addressing the impact of night shiftwork on human health.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713089","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":"Correction to: Biomarkers of cellular senescence and major health outcomes in older adults.","authors":"Steven R Cummings, Li-Yung Lui, Zaira Aversa, Theresa Mau, Roger A Fielding, Elizabeth J Atkinson, Sheena Patel, Nathan LeBrasseur","doi":"10.1007/s11357-025-01619-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01619-4","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709514","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}