{"title":"Plasma proteomics-based organ-specific aging for all-cause mortality and cause-specific mortality: a prospective cohort study.","authors":"Renjia Zhao, Heyang Lu, Huangbo Yuan, Shuaizhou Chen, Kelin Xu, Tiejun Zhang, Zhenqiu Liu, Yanfeng Jiang, Chen Suo, Xingdong Chen","doi":"10.1007/s11357-024-01411-w","DOIUrl":"10.1007/s11357-024-01411-w","url":null,"abstract":"<p><p>Individual's aging rates vary across organs. However, there are few methods for assessing aging at organ levels and whether they contribute differently to mortalities remains unknown. We analyzed data from 45,821 adults in the UK Biobank, using plasma proteomics and machine learning to estimate biological ages for 12 major organs. The differences between biological age and chronological age, referred to as \"age gaps,\" were calculated for each organ. Partial correlation analyses were used to assess the association between age gaps and modifiable factors. Adjusted multivariable Cox regression models were applied to examine the association of age gaps with all-cause mortality, cause-specific mortalities, and cancer-specific mortalities. We reveal a complex network of varied associations between multi-organ aging and modifiable factors. All age gaps increase the risk of all-cause mortality by 6-60%. The risk of death varied from 5.54 to 29.18 times depending on the number of aging organs. Cause-specific mortalities are associated with certain organs' aging. For mental diseases mortality, and nervous system mortality, only brain aging exhibited a significant increased risk of HR 2.38 (per SD, 95% CI: 2.06-2.74) and 1.99 (per SD, 95% CI: 1.84-2.16), respectively. Age gaps of stomach were also a specific indicator for gastric cancer. Eventually, we find that an organ's biological age selectively influences the aging of other organ systems. Our study demonstrates that accelerated aging in specific organs increases the risk of mortality from various causes. This provides a potential tool for early identification of at-risk populations, offering a relatively objective method for precision medicine.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1411-1423"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545060","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-11-07DOI: 10.1007/s11357-024-01419-2
Yue Ji, Hao Sun, Yingda Wang, Yanhui Li, Rennv Piao, Li Bu, Hui Xu
{"title":"Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China.","authors":"Yue Ji, Hao Sun, Yingda Wang, Yanhui Li, Rennv Piao, Li Bu, Hui Xu","doi":"10.1007/s11357-024-01419-2","DOIUrl":"10.1007/s11357-024-01419-2","url":null,"abstract":"<p><p>The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"2275-2292"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589922","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-10-02DOI: 10.1007/s11357-024-01370-2
J Sophie Sagawe, Verity I P Loake, Peter J M Openshaw, Paul Kemp, Fiona J Culley
{"title":"Aging enhances pro-atrogenic gene expression and skeletal muscle loss following respiratory syncytial virus infection.","authors":"J Sophie Sagawe, Verity I P Loake, Peter J M Openshaw, Paul Kemp, Fiona J Culley","doi":"10.1007/s11357-024-01370-2","DOIUrl":"10.1007/s11357-024-01370-2","url":null,"abstract":"<p><p>Aging and many age-related health conditions are associated with skeletal muscle loss. Furthermore, older adults are more susceptible to severe respiratory infections, which can in turn lead to muscle wasting. The mechanisms by which respiratory viral infection can impact skeletal muscle in older adults are not well understood. We determined the effects of acute infection with respiratory syncytial virus (RSV) on the lung and skeletal muscle of aged mice. RSV infection caused more severe disease in aged mice with enhanced weight loss, reduced feeding, higher viral load, and greater airway inflammation. Aged but not young mice showed decreased leg muscle weight at the peak of illness and decreased size of leg muscle fibers. Aged mice increased muscle-specific expression of atrophy-promoting enzymes (Atrogin-1 and MuRF-1) and failed to increase the rate of muscle protein synthesis during RSV infection. In aged mice, the changes in Atrogin-1 and MuRF-1 gene expression in skeletal muscle correlated with IL-6 levels in the lungs. These findings indicate that RSV infection of aged mice provides a model for studying the diverse adverse systemic consequences of respiratory viral infections on health and wellbeing in older adults.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1485-1500"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361421","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-10-01DOI: 10.1007/s11357-024-01335-5
Angelina R Sutin, Martina Luchetti, Yannick Stephan, Norma Mansor, Tiia Kekäläinen, Antonio Terracciano
{"title":"Purpose in life and grip strength: An individual-participant meta-analysis of 115,972 participants from 24 countries across four continents.","authors":"Angelina R Sutin, Martina Luchetti, Yannick Stephan, Norma Mansor, Tiia Kekäläinen, Antonio Terracciano","doi":"10.1007/s11357-024-01335-5","DOIUrl":"10.1007/s11357-024-01335-5","url":null,"abstract":"<p><p>This research examines the replicability and generalizability of the association between purpose in life and grip strength. An individual-participant meta-analysis of 27 samples (total N=115,972) from 24 countries that spanned four continents (Asia, Europe, North and South America) with self-reported purpose in life and dynamometer-assessed grip strength. Purpose in life was associated with stronger grip strength in every sample and aggregated in a random-effects meta-analysis (meta-analytic estimate=.06, p<.001). The association was similar across samples from different world regions and not moderated by methodological factors (e.g., scale content). The association was apparent across age, sex, race, and education and slightly stronger among males and participants with relatively less education. Every standard deviation in purpose was associated with a 23% lower likelihood of weak grip strength (meta-analytic OR=.81, 95% CI=.79-.84, p<.001) based on a standard threshold. Purpose in life is associated with grip strength, a marker of overall musculoskeletal health. The association replicates across diverse locations around the world and generalizes across sociodemographic groups.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1735-1745"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361423","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-10-22DOI: 10.1007/s11357-024-01373-z
Emma L Gay, Paul M Coen, Stephanie Harrison, Reagan E Garcia, Yujia Susanna Qiao, Bret H Goodpaster, Daniel E Forman, Frederico G S Toledo, Giovanna Distefano, Philip A Kramer, Sofhia V Ramos, Anthony J A Molina, Barbara J Nicklas, Steven R Cummings, Peggy M Cawthon, Russell T Hepple, Anne B Newman, Nancy W Glynn
{"title":"Sex differences in the association between skeletal muscle energetics and perceived physical fatigability: the Study of Muscle, Mobility and Aging (SOMMA).","authors":"Emma L Gay, Paul M Coen, Stephanie Harrison, Reagan E Garcia, Yujia Susanna Qiao, Bret H Goodpaster, Daniel E Forman, Frederico G S Toledo, Giovanna Distefano, Philip A Kramer, Sofhia V Ramos, Anthony J A Molina, Barbara J Nicklas, Steven R Cummings, Peggy M Cawthon, Russell T Hepple, Anne B Newman, Nancy W Glynn","doi":"10.1007/s11357-024-01373-z","DOIUrl":"10.1007/s11357-024-01373-z","url":null,"abstract":"<p><p>Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher = greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher = greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N = 873) were 76.3 ± 5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo) were associated with lower perceived physical fatigability, all p < 0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE Fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS ≥ 25, RPE Fatigability ≥ 12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p < 0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the ex vivo measures (p < 0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1999-2013"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463215","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-10-21DOI: 10.1007/s11357-024-01388-6
In Gyoung Ju, Seungmin Lee, Hyeri Im, Jae Hoon Kim, Hyeyoon Eo, Myung Sook Oh
{"title":"Artemisiae Iwayomogii Herba mitigates excessive neuroinflammation and Aβ accumulation by regulating the pro-inflammatory response and autophagy-lysosomal pathway in microglia in 5xFAD mouse model of Alzheimer's disease.","authors":"In Gyoung Ju, Seungmin Lee, Hyeri Im, Jae Hoon Kim, Hyeyoon Eo, Myung Sook Oh","doi":"10.1007/s11357-024-01388-6","DOIUrl":"10.1007/s11357-024-01388-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) presents a growing societal challenge, driven by an aging population. It is characterized by neurodegeneration linked to β-amyloid (Aβ) and tau protein aggregation. Reactive glial cell-mediated neuroinflammation exacerbates disease progression by facilitating the accumulation of Aβ and impairing its clearance, thus highlighting potential therapeutic targets. Aerial parts of Artemisia iwayomogi (AIH), a kind of mugwort, has been consumed as a medicinal herb in East Asia for relieving inflammation-related diseases. Previously, AIH was found to exert potent inhibitory effects on neuroinflammation. This study aimed to examine whether AIH mitigates AD pathogenesis by regulating neuroinflammation and reducing Aβ deposition. AIH treatment to primary mixed glial cultures attenuated the pro-inflammatory responses evoked by Aβ stimulation. When treated to 5 × familial AD (5xFAD) mice, AIH improved learning and cognitive ability and reduced Aβ burden in the brain. AIH suppressed glial overactivation, as well as inhibited the expressions of pro-inflammatory mediators in the brain. Moreover, AIH regulated AKT signaling and elevated the expression of autophagy-lysosomal mediators in vitro. It was confirmed that lysosome-associated membrane protein 1 (LAMP1) was increased in the Aβ-associated microglia in the mouse hippocampus. Finally, it was observed that tau phosphorylation was alleviated, and synaptic protein expression was increased in AIH-treated 5xFAD mice. Overall, this study demonstrated that AIH ameliorated excessive neuroinflammation and Aβ accumulation by regulating microglial activation and autophagy-lysosomal pathway, thereby suggesting AIH as a promising therapeutic candidate for AD treatment.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"1957-1972"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463210","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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-10-04DOI: 10.1007/s11357-024-01349-z
Martina Vinicki, Tea Pribić, Frano Vučković, Azra Frkatović-Hodžić, Isaac Plaza-Andrades, Francisco Tinahones, Joseph Raffaele, José Carlos Fernández-García, Gordan Lauc
{"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}
GeroSciencePub Date : 2025-04-01Epub Date: 2024-11-04DOI: 10.1007/s11357-024-01398-4
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
{"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}
GeroSciencePub Date : 2025-03-29DOI: 10.1007/s11357-025-01625-6
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
{"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}