GeroScience最新文献

{"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}

{"title":"Growth hormone–deficient Ames dwarf mice resist sarcopenia and exhibit enhanced endurance running performance at 24 months","authors":"Matthew J. Johnston, Sharlene G. Rakoczy, LaDora V. Thompson, Holly M. Brown-Borg","doi":"10.1007/s11357-025-01630-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01630-9","url":null,"abstract":"<p>Ames dwarf mice (<i>df/df</i>) live 50% longer than normal littermates due to a genetic defect in growth hormone (GH) signaling. The enhanced longevity of Ames dwarfs has been studied extensively in an endocrinological context of cellular metabolism and increased resistance to oxidative stress (Bartke. World J Mens Health 37(1):19, 8; Bartke 2; BartkeJ Am Aging Assoc 23(4):219, 10; Bartke. World J Mens Health 39(3):454-465, 11; Brown-Borg et al. Nature 384(6604):33-33, 1; Masternak et al. 2018). However, the skeletal muscle system is relatively unexplored, the quality of which dictates metabolic homeostasis, permits movement and exercise, and exerts paracrine effects on other organs (Delmonico and Beck Am J Lifestyle Med 11(2):167-181, 25; Evans et al. GeroScience 46(1):183, 26; Kim and Kim. Endocrinol Metab (Seoul) 35(1):1-6, 15; Masternak et al. 2018). Here, we characterize the fitness capacity and skeletal muscle morphology of Ames mice to determine if previously established longevous effects of GH deficiency extend to skeletal muscle tissue. Mutually exclusive, age-matched cohorts of male Ames mice and wildtype controls performed grip strength, rotarod, and endurance running experiments over 6 months. The largest difference in physical performance was observed in endurance running capacity, where dwarf mice outperformed wildtype controls increasingly with age. Tibialis anterior (TA) muscles were evaluated for myofiber size, quality, and environment. Ames mice show reduced myofiber cross-sectional area (CSA) paired with increased myofibers per muscle. Dwarf myofiber populations are less heterogenous in size and seemingly resist sarcopenia, as skeletal muscle from aged individuals shows youthful morphological resemblance in mean myofiber CSA, size frequency distribution, and presence of fibrotic tissue. Declines in fitness performance and myofiber integrity were observable in age-matched wildtype controls. Utilizing an established longevity model to investigate skeletal muscle function and morphology is a novel approach to gaining insight into the seemingly inverse relationship between GH signaling and mammalian longevity.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"212 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712733","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":"Paying attention to proprioception: age affects ankle proprioception and the attentional demand of proprioceptive processing in sedentary adults","authors":"Marie Julie Vermette, Emmeline Paré, François Prince, Julie Messier","doi":"10.1007/s11357-025-01609-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01609-6","url":null,"abstract":"<p>Ankle proprioception and attentional resources are crucial for maintaining balance and safely driving. However, research exploring the age-related integrity of ankle proprioception has yielded conflicting results, while the attentional demand of proprioceptive processing in seniors remains underexplored. We investigated how aging affects the interaction between proprioception and attention in healthy sedentary adults using a novel dual-task paradigm. Sedentary old and young adults performed an ipsilateral proprioceptive-matching task with a long target encoding time and a cognitive-attentional subtraction task. These tasks were performed alone (single-task) or simultaneously (dual-task). Older adults showed significantly lower ankle proprioceptive accuracy and consistency in dorsiflexion compared to young adults under the single-task condition. Hence, the matching inaccuracies of seniors were more pronounced relative to young adults, when performing the proprioceptive and cognitive-attentional tasks simultaneously. Importantly, both age groups demonstrated similar cognitive performance in the single-task. However, while younger adults maintained their performance during dual-tasking, seniors showed markedly lower cognitive-attentional scores in the dual compared to the single-task condition. Thus, their dual-task costs were higher than those of young adults. Our findings of impaired ankle proprioception in sedentary older adults in the single-task underline the importance of controlling participants’ physical lifestyles and demonstrate that this novel paradigm is highly sensitive to age-related proprioceptive changes. Furthermore, the substantial decline in both proprioceptive and cognitive performance during dual-tasking suggests that sedentary older adults mobilize increasingly large cognitive-attentional resources to process proprioception. This dual-task paradigm may serve as a useful biomarker to predict falls and driving accidents in older populations.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"183 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703175","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":"WormRACER: Robust Analysis by Computer-Enhanced Recording","authors":"Bennett T. Van Camp, Quinn N. Zapata, Sean P. Curran","doi":"10.1007/s11357-025-01631-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01631-8","url":null,"abstract":"<p>The pace of scientific high-throughput screening for age-related phenotypes requires the need for developing streamlined and efficacious methods of measuring and quantifying physiological outcomes and at a scale that enables adequate statistical power to measure the variation in populations. Here, we introduce Worm Robust Analysis by Computer-Enhanced Recording (WormRACER), a computationally efficient computer vision software capable of extracting six different crawling and swimming metrics from many animals simultaneously, including worm area, worm length, crawling speed, swimming speed, dynamic amplitude, and wave initiation rate (thrashing). Additionally, we developed a web-based portal that provides metric averages and metric vs time graphs that allow for simple data analysis and quality assurance. WormRACER will facilitate the rapid and quantitative characterization of movement as a facile measurement of healthspan enabling power for high-throughput screening of genetic, environmental, and pharmacological interventions.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"35 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712734","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}