GeroScience最新文献

{"title":"Association between dietary (poly)phenol intake and the ATHLOS Healthy Ageing Scale in the Polish arm of the HAPIEE study.","authors":"Urszula Stepaniak, Giuseppe Grosso, Maciej Polak, Barbara Gradowicz-Prajsnar, Magdalena Kozela, Martin Bobak, Albert Sanchez-Niubo, Denes Stefler, Josep Maria Haro, Andrzej Pająk","doi":"10.1007/s11357-024-01275-0","DOIUrl":"10.1007/s11357-024-01275-0","url":null,"abstract":"<p><p>Inverse association between (poly)phenol intake and age-related disorders has been demonstrated; however, little is known whether they affect comprehensively assessed healthy aging. The aim of this study was to evaluate the associations between the intake of (poly)phenol (including selected classes and subclasses) and healthy aging scores related to biopsychosocial aspects of health and functioning. A cross-sectional study was performed using data on 9774 randomly selected citizens of Krakow (Poland) who were 45-69 years of age. Dietary (poly)phenol intake was evaluated using a food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. The healthy aging scores were estimated from the ATHLOS Healthy Ageing Scale (HAS) developed by the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) consortium. Beta coefficients were calculated using multivariable linear regression models. In multivariable adjusted models, there were significant positive associations between the ATHLOS HAS score and intake of total (poly)phenols (b per increase of 100 mg/day = 0.081; 95% CI, 0.050; 0.112) and among main classes of (poly)phenols with phenolic acids (b = 0.139; 95% CI, 0.098; 0.180). Intake of remaining classes of (poly)phenols (flavonoids, lignans, stilbenes, and others) was not related to the ATHLOS HAS score. Among individual classes studied, hydroxycinnamic acids, flavonols, flavones, and dihydrochalcones were associated with better healthy aging. The findings suggest the beneficial effect of total dietary (poly)phenol and some classes and subclasses of (poly)phenol intake in terms of healthy aging in Poland. These findings should be confirmed in other settings and with prospective data.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"3241-3253"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right anterior insula ASL hypoperfusion as a diagnostic biomarker of prodromal and mild dementia with Lewy bodies: preliminary evidence using a Bayesian approach.","authors":"Golda Gommel, Ludovic Jeanjean-Dormegny, Clément de Crespin de Billy, Olivier Mainberger, Augustin Moreau, Alexandre Obrecht, Rémi Vernet, Ilia Humbert, Benoit Schorr, Candice Muller, Catherine Demuynck, Paulo Loureiro de Sousa, Frédéric Blanc, Jack Foucher","doi":"10.1007/s11357-024-01288-9","DOIUrl":"10.1007/s11357-024-01288-9","url":null,"abstract":"<p><p>Identifying and validating a biomarker with high specificity in early-stage dementia with Lewy bodies (DLB) using a feasible method is crucial to enhance the current suboptimal diagnostic procedure. Previous research revealed abnormalities, including hypoperfusion in the right anterior insular cortex at group level, in prodromal DLB. Exploring hypoperfusion of the right anterior insula, at an individual-level and assessing its relevance as a potential imaging biomarker in early DLB, has, to our knowledge, not been investigated. Our preliminary study aims to assess the feasibility of the technique and to provide a methodological framework for further investigation. We assessed the feasibility and accuracy of the hypoperfusion of the right anterior insula per arterial spin labelling magnetic resonance imaging (ASL-MRI) as a diagnostic biomarker in early DLB and provided rough estimates of its sensitivity and specificity. Defining the region of interest based on previous research, we established the biomarker as the hypoperfusion of the right anterior insula. Discriminative and analytical performances were assessed in comparison to a control group of treatment-resistant depression patients. Bayesian diagnostic reasoning was employed to assess the biomarker diagnostic usability in early DLB in two scenarios: healthy elderly controls and mild cognitive impairment. Additionally, we updated probabilities by integrating data from the Mayo-clinic cognitive fluctuations scale and real-time quaking-induced conversion (RT-QuIC) α-synuclein data. Lastly, a whole-brain perfusion analysis of DLB patients was conducted to identify further brain regions with discriminative abilities. We successfully replicated the right anterior insular hypoperfusion (RAI-Hypo) in all DLB patients at the individual level. The overall sensitivity of the biomarker was 96%, and the specificity was 92%. Bayesian testing revealed the biomarker's highest performance in early-stage DLB with cognitive fluctuations, showcasing a diagnostic potential associated with a high precision and moderate accuracy. In a cognitively non-impaired population, the RAI-Hypo showed a limited usability and lacked in selectivity to qualify as a screening tool. The exploratory whole-brain analysis revealed perfect discriminative capacities in the bilateral anterior insulae and the left inferior parietal lobule. Further studies are needed to confirm our preliminary results. If performance is maintained in subsequent studies and is compared to a more suitable control population, the proposed biomarker may be eventually sufficient to discriminate early-stage DLB from non-DLB.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"3255-3276"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Better objective sleep quality is associated with higher gut microbiota richness in older adults.","authors":"Maria Teresa Wijaya, Ji-Tseng Fang, Geng-Hao Liu, Yuan-Ming Yeh, Ning-Hung Chen, Chih-Ming Lin, Kuain-Yi Wu, Chih-Mao Huang, Shwu-Hua Lee, Tatia M C Lee","doi":"10.1007/s11357-025-01524-w","DOIUrl":"10.1007/s11357-025-01524-w","url":null,"abstract":"<p><p>Aging is associated with disrupted sleep patterns, such as fragmented sleep and reduced efficiency, leading to negative health outcomes. There is evidence of a bidirectional relationship between sleep and gut microbiota, which plays a key role in the gut-brain axis and overall health. However, studies on this relationship in older adults have limited generalizability and show conflicting results, highlighting the need for further research. This study aimed to investigate the associations between sleep quality and gut microbiota composition in healthy Chinese older adults using subjective and objective sleep measures to capture various aspects of sleep quality and explore potential impacts on emotional well-being and cognitive performance. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, while objective sleep quality was measured with actigraphy. Gut microbiota sequencing was performed on stool samples. The results show a robust positive association between gut microbiota richness and objective sleep quality in older adults, independent of subjective sleep quality and demographics, lifestyle, and health covariates. However, no significant link was found between gut microbiota richness and subjective sleep quality. Specific taxa like Bacteroidetes, Ruminococcus, Collinsella, Veillonella, and Holdemania were tentatively linked to sleep quality. These findings emphasize the connection between sleep quality and gut microbiota composition in older adults with potential research and clinical implications, improving our understanding of the mechanisms underlying the sleep-gut microbiota relationship and guiding the development of interventions for improving both sleep quality and gut health in older adults.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"4121-4137"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive myocardial work as an independent predictor of postprocedural NT-proBNP in elderly patients undergoing transcatheter aortic valve replacement.","authors":"Zsuzsanna Ladányi, Tímea Bálint, Alexandra Fábián, Adrienn Ujvári, Tímea Katalin Turschl, Dávid Nagy, Éva Straub, Csaba Fejér, Endre Zima, Astrid Apor, Anikó Ilona Nagy, Tímea Szigethi, Roland Papp, Levente Molnár, Attila Kovács, Mihály Ruppert, Bálint Károly Lakatos, Béla Merkely","doi":"10.1007/s11357-024-01302-0","DOIUrl":"10.1007/s11357-024-01302-0","url":null,"abstract":"<p><p>Aortic stenosis has become the most prevalent valvular disease with increasing life expectancy and the ageing of the population, representing a significant clinical burden for health care providers. Its treatment has been revolutionized by transcatheter aortic valve replacement (TAVR) as a safe and minimally invasive option for elderly patients. Left ventricular (LV) functional measurement is of particular importance before TAVR, however, increased afterload significantly influences the conventional echocardiographic parameters. Non-invasive myocardial work examines myocardial deformation in the context of instantaneous LV pressure, thus, it might be a more reliable measure of LV function. Accordingly, we aimed to study non-invasive myocardial work and its relationship with functional outcome following TAVR.We enrolled 90 TAVR candidates (80 [75-84] years; 44% female). Using echocardiography, we quantified ejection fraction (EF), global longitudinal strain (GLS), global myocardial work index (GWI) and global constructive work (GCW) before and 12 months after the procedure. Serum NT-proBNP levels were also measured. EF did not change (52.6 ± 13.1 vs. 54.2 ± 10.5%; p = 0.199), while GLS increased (-13.5 ± 4.6 vs. -15.2 ± 3.8%; p < 0.001). GWI decreased (1913 ± 799 vs. 1654 ± 613 mmHg%; p < 0.001) and so did GCW (2365 ± 851 vs. 2177 ± 652 mmHg%; p = 0.018). History of atrial fibrillation (AF) (β = 0.349) and preprocedural GCW (β = -0.238) were independent predictors of postprocedural NT-proBNP (p < 0.001).GLS, GWI and GCW changed after TAVR while there was no alteration in EF. The preprocedural GCW and history of AF were independent predictors of postprocedural NT-proBNP. Accordingly, myocardial work indices may help patient selection and the prediction of the functional outcome in this population.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"3311-3323"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The resistance of domestic canine skin-derived fibroblasts to oxidative and non-oxidative chemical injury: implications of breed and body size.","authors":"James M Harper, Megan Hicks, Ana Gabriela Jiménez","doi":"10.1007/s11357-024-01358-y","DOIUrl":"10.1007/s11357-024-01358-y","url":null,"abstract":"<p><p>Small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. Underlying this observed physiological difference across domestic dogs, there must also be differences at other levels of organization that could lead to elucidating what accounts for the disparity in aging rates and life span within this species. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated. Here, we cultured dermal fibroblasts from large and small breed dogs from both young and old age categories and examined the degree of resistance to multiple sources of cytotoxic stress. This included heat (42 °C), paraquat, cadmium, and hydrogen peroxide for increasing amounts of time (heat) or increasing concentrations (chemical stressors). We hypothesized that small breed dogs, with longer lifespans, would have greater cellular resistance to stress compared with large breed dogs. Final sample sizes include small puppies (N = 18), large puppy (N = 32), small old (N = 11), and large old (N = 23) dogs. Using a 2 (donor size) by 2 (donor age) between-subjects multivariate analysis of variance, we found that the values for the dose that killed 50% of the cells (LD₅₀) were not significantly different based on donor size (p = 0.45) or donor age (p = 0.20). The interaction was also not significant (p = 0.47). Interestingly, we did find that the degree of resistance to cadmium toxicity was significantly correlated with the degree of resistance to both heat and hydrogen peroxide, but not paraquat (p < 0.01 for both). These data suggest that cellular stress resistance does not differ among domestic dogs as a function of size or age, pointing to other cellular pathways as the mechanistic basis for the observed differences in lifespan.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"3665-3675"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the geroprotective potential of Monarda didyma L.: insights from in vitro studies and a randomized clinical trial on slowing biological aging and improving quality of life.","authors":"Manuela Campisi, Luana Cannella, Omar Paccagnella, Alessandra R Brazzale, Alberto Agnolin, Torsten Grothe, Julia Baumann, Sofia Pavanello","doi":"10.1007/s11357-025-01580-2","DOIUrl":"10.1007/s11357-025-01580-2","url":null,"abstract":"<p><p>Aging is driven by fundamental mechanisms like oxidative stress, telomere shortening and changes in DNA methylation, which together prepare the ground for age-related diseases. Botanical extracts, rich in bioactive phytoconstituents, represent a promising resource for developing therapies that target these mechanisms to promote healthy aging. This study explores the geroprotective potential of Monarda didyma L. extract. In vitro analyses revealed the extract's strong antioxidant activity, ability to reduce telomere shortening, and capacity to protect against DNA damage, thereby decreasing cellular senescence and improving endothelial function. The randomized, double-blind clinical trial demonstrated that daily oral supplementation with the extract significantly improved leukocyte telomere length (LTL) and stabilized DNA methylation age (DNAmAge) in the intervention group, while the placebo group experienced accelerated epigenetic aging and hypermethylation of critical age-related genes (ELOVL2 and FHL2). The intervention group also reported enhanced quality of life, particularly in the physical domain, along with improved movement and quality sleep indices detected by questionnaire and wearable sensors. These compelling findings position Monarda didyma L. extract as a powerful candidate for future geroprotective therapies, with the potential to significantly impact healthy aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"4253-4290"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a multimorbidity health conditions outcome index for caloric restriction interventional studies in older adults: a preliminary investigation in an observational cohort study.","authors":"Michael E Miller, Haiying Chen, Mark A Espeland, Fang-Chi Hsu, Denise K Houston, Anne B Newman, W Jack Rejeski, Barbara J Nicklas, Stephen B Kritchevsky","doi":"10.1007/s11357-025-01708-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01708-4","url":null,"abstract":"<p><p>Using multiple sources, we provide the conceptual justification and statistical support for a multimorbidity outcome associated with obesity-related conditions, which we term the Health Conditions Index (HCI). This index was designed to capture the health effects of multi-year studies of caloric restriction for older adults with BMIs in the overweight or obesity classification. We used a subset of participants in the Health, Aging and Body Composition Cohort Study to evaluate multiple aspects of the index and its components over 5 years of follow-up. The 937 participants in the subset had an average age of 73 years and a BMI of 30.7 kg/m²; 53% were female and 43% were Black; 80% were hypertensive and 14% had type 2 diabetes. Results demonstrated that the components of the index were consistently related to initial BMI and percent body fat on cohort entry, generally showed an increasing prevalence over the 5-year follow-up, and, as a composite index, exhibited an association between faster progression and higher initial levels of age, BMI, and percent body fat. Further, the initial HCI was associated with a statistically significant increase in the rate of mortality over 5 years of follow-up (hazard ratio = 1.22, 95% CI 1.04 to 1.44). By using outcomes like the HCI, clinical trials of caloric restriction in older adults may gain a better understanding of how intentional weight loss relates to future risk of multiple chronic conditions associated with aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186861","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":"MicroBayesAge: a maximum likelihood approach to predict epigenetic age using microarray data.","authors":"Nicole Nolan, Megan Mitchell, Lajoyce Mboning, Louis-S Bouchard, Matteo Pellegrini","doi":"10.1007/s11357-025-01716-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01716-4","url":null,"abstract":"<p><p>Certain epigenetic modifications, such as the methylation of CpG sites, can serve as biomarkers for chronological age. Previously, we introduced the BayesAge frameworks for accurate age prediction through the use of locally weighted scatterplot smoothing (LOWESS) to capture the nonlinear relationship between methylation or gene expression and age, and maximum likelihood estimation (MLE) for bulk bisulfite and RNA sequencing data. Here, we introduce MicroBayesAge, a maximum likelihood framework for age prediction using DNA microarray data that provides less biased age predictions compared to commonly used linear methods. Furthermore, MicroBayesAge enhances prediction accuracy relative to previous versions of BayesAge by subdividing input data into age-specific cohorts and employing a new two-stage process for training and testing. Additionally, we explored the performance of our model for sex-specific age prediction which revealed slight improvements in accuracy for male patients, while no changes were observed for female patients.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186862","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 the Planetary Health Diet Index and growth differentiation factor-15: the Seniors ENRICA-2 cohort.","authors":"María Del Carmen Aznar de la Riera, Rosario Ortolá, Blanca Fabre-Estremera, Antonio Buño-Soto, Fernando Rodríguez-Artalejo, Mercedes Sotos-Prieto","doi":"10.1007/s11357-025-01712-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01712-8","url":null,"abstract":"<p><p>The growth differentiation factor-15 (GDF-15) is an inflammaging biomarker, predictor of cardiovascular disease (CVD), and several other non-communicable diseases (NCD) that represent the main causes of death globally, for which prevention is essential. Current worldwide threats include NCD and environmental burden, where diet is a key determinant. Therefore, the EAT-Lancet Commission developed the Planetary Health Diet Index (PHDI), a dietary pattern designed to ameliorate human and environmental health. The objective of the study was to evaluate the association between the PHDI and serum concentrations of GDF-15 in older adults. Study participants were 2497 people aged + 65 years from the Seniors-ENRICA-2 study. Food consumption was obtained through a validated diet history, and adherence to the PHDI was estimated with a score of 15 food groups (range 0-140), where higher scores indicated better adherence. Analyses for the association between the PHDI and GDF-15 concentrations were performed using multivariable linear regression models, adjusting for main potential confounders. The PHDI showed an inverse dose-response association with GDF-15 concentrations. Compared with participants in the lowest quartile of the PHDI, those in the highest quartile had a mean percentage difference (95% CI) of - 6.8% (- 11.1, - 2.4) in GDF-15 concentrations. The mean percentage difference (95% CI) per 20-point increase of adherence was - 4.4% (- 7.7, - 0.9). Consumption of whole grains, fruits, nuts, and a low intake of trans and saturated fat were important drivers of this association. Results remained robust after adjustment for other inflammation (interleukin 6), renal and cardiac (creatinine, NT-proBNP, cardiac troponin T) biomarkers, and after excluding participants with CVD, type 2 diabetes, and obesity. The PHDI was associated with lower concentrations of GDF-15. Adopting the PHDI may be a useful approach to reduce chronic inflammation and target NCD prevention in the older adult population, while staying within planetary boundaries.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191715","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":"Citrinin delays muscle aging and extends lifespan in C. elegans and prevents senescence in C2C12 through SKN-1/Nrf2 activation.","authors":"Yejin Cho, Woo Jin Lee, Hee Soo Kim, Hyo-Deok Seo, Chang Hwa Jung, Jiyun Ahn, Hong-Seok Son, Jeong-Hoon Hahm","doi":"10.1007/s11357-025-01713-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01713-7","url":null,"abstract":"<p><p>Sarcopenia, a condition characterized by the loss of muscle mass and function with aging, is linked to various health issues including diabetes and increased risk of falls and fractures. Currently, there is no FDA-approved treatment exists for sarcopenia. Citrinin, a natural compound present in daily dietary sources such as grains, has not been well characterized for its biological effects on muscle aging. Here, we found that citrinin exhibits beneficial effects in delaying muscle aging in both Caenorhabditis elegans (C. elegans) and mouse muscle cells (C2C12). Citrinin attenuated the decline of muscle activities in aged C. elegans, including pharyngeal pumping, body bending, maximum velocity, and locomotor abilities. It also prevented myosin protein loss in C. elegans muscle cells. Citrinin activated SKN-1 (the C. elegans ortholog of mammalian Nrf2), which mediated the prevention of myosin protein loss and the decline in muscle activities. Additionally, citrinin extended the median lifespan of C. elegans via SKN-1. Furthermore, we found that IRE-1 mediated the effects of citrinin on SKN-1 activation and that citrinin delayed aging through the IRE-1/SKN-1 pathway. However, citrinin prevented muscle aging in a UPR^ER (unfolded protein response of the endoplasmic reticulum) independent manner. In addition, in C2C12 cells, citrinin reduced the number of β-galactosidase-positive stained cells, prevented nuclear expansion, and decreased p21 expression under etoposide-induced senescence conditions, while also activating Nrf2. These findings suggest that citrinin is a potential candidate compound for preventing muscle aging by inducing well-conserved stress response mechanisms from C. elegans to humans. Thus, we propose that citrinin may have positive effects on promoting healthy aging in humans.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186860","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}