GeroScience最新文献

{"title":"Decoding cognitive aging: how white matter tracts and demographics distinguish potential Super-Agers","authors":"Mohammad Fili, Parvin Mohammadiarvejeh, Guiping Hu, Auriel A. Willette","doi":"10.1007/s11357-025-01566-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01566-0","url":null,"abstract":"<p>Most adults experience age-related cognitive decline. However, “Positive-Agers” exhibit superior cognition compared to their age-matched peers. Distinguishing between those with superior cognitive performance and those with cognitive decline over time could better inform treatment therapies in older adults. We developed an algorithm called <i>Opti</i>mal <i>C</i>ognitive <i>S</i>coring (OptiCS) that accurately differentiates “Positive-Agers” from “Cognitive Decliners.” This study draws on a cohort of 5797 participants longitudinally enrolled in the UK Biobank. Using a predictive pipeline, OptiCS could strongly differentiate Positive-Agers versus Cognitive Decliners (area under the curve, or AUC of 83%). The top diffusion MRI attributes highlighted tracts implicated in pathological aging, including the fornix from the hippocampus, the tapetum from the splenium of the corpus callosum, and other key tracts. This study provides three key insights: (I) The proposed algorithm offers a robust cognitive scoring system for subtle cognitive changes, (II) OptiCS can use diffusion MRI to accurately gauge cognitive performance, and (III) OptiCS provides a predictive framework for early detection of cognitive decline.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"82 1 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495380","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":"Improving care interactions (and training) in nursing homes with artificial intelligence","authors":"Marie Lefelle, Mouny Samy Modeliar","doi":"10.1007/s11357-025-01557-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01557-1","url":null,"abstract":"<p>As the population continues to age, nursing homes will increasingly play a key role in caring for dependent individuals. To enhance the well-being of the elderly, it is crucial to focus on the language skills used during care interactions. However, issues such as the taboo surrounding dependency, scandals involving private nursing home management, the pressure for caregiver efficiency, and the variety of care contexts make monitoring these skills challenging. One way to address this is by collecting in situ data, supervised by language researchers and caregivers specialized in elderly care. This is the approach we have followed: the data collected was then analyzed using machine learning models to provide caregivers with crucial insights for improving care outcomes. Our research highlights the importance of specific factors in language-based interactions, especially in varied care situations. Notably, we emphasize the careful use of humor and the impact of caregiver experience on the success of care sessions. Consequently, we advocate for caregiver training that is grounded in real-life practice, focusing on context adaptation, active listening, and dialogue with residents.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"27 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485878","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":"SenSkin™: a human skin-specific cellular senescence gene set","authors":"Saranya P. Wyles, Grace T. Yu, Clarisse Ganier, Tamar Tchkonia, Magnus D. Lynch, George A. Kuchel, James L. Kirkland","doi":"10.1007/s11357-025-01568-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01568-y","url":null,"abstract":"<p>Cellular senescence gene sets have been leveraged to overcome the inadequate sensitivity or specificity of single markers. However, growing evidence of heterogeneity among tissues in senescent cell phenotypes and gene expression profiles has highlighted the need for tissue-specific gene sets. SenSkin™ was curated by an expert review of literature on cellular senescence in the skin and characterized with pathway analysis. To validate SenSkin™, it was evaluated for enrichment with chronological aging in a bulk RNA-sequencing (RNA-seq) dataset and a pseudobulk RNA-seq dataset. Further, changes to SenSkin™ in different skin cell types with photoaging were evaluated in two single-cell RNA-seq datasets. SenSkin™ predominantly included genes related to the senescence-associated secretory phenotype (SASP), which were associated with metabolism and multiple aspects of immune responses. SenSkin™ was more enriched in chronologically aged skin than other commonly used cellular senescence and aging gene sets. In scRNA-seq, SenSkin™ displayed significant upregulation due to photoaging in ten skin cell types. In conclusion, SenSkin™ is a human skin-specific senescence gene set validated in chronological aging and photoaging, which may be more effective at detecting senescent cells in the skin than non-tissue-specific gene sets.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"128 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485523","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":"Awareness, knowledge, and motivations about lifespan, healthspan, and Healthy Longevity Medicine in the general population: the HEalthy LOngevity (HELO) conceptual framework","authors":"Belinda Wang, Anna Szücs, Elena Sandalova, E. J. Horberg, Paul A. O’Keefe, Louis Island, Hans J. Meij, Sonny Rosenthal, Andrea B. Maier","doi":"10.1007/s11357-025-01562-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01562-4","url":null,"abstract":"<p>The global population is ageing and the gap between lifespan (total years lived) and healthspan (years lived free of diseases) is increasing. Healthy Longevity Medicine (HLM) is an approach to optimise health and healthspan, and it has substantial public health implications. Despite those implications, the understanding of public perspectives on this field is lacking. The HEalthy LOngevity (HELO) framework was developed through a literature review guided by expert discussions across disciplines to include evidence-based concepts of health-related decision-making, ageing, and HLM. The framework organises concepts into three components. The first two components, awareness and knowledge, explore public perception and understanding of the healthy longevity field, respectively. The third component, motivations, reflects factors underlying motivations towards healthy longevity. These include personality, current behaviours, personal values and beliefs, and health-related perceptions. The framework outlines the theoretical foundation to explore public knowledge and interest in healthy longevity. The framework will be refined based on findings from qualitative focus groups in Singapore and then applied to quantitative population surveys globally. These HELO initiatives aim to inform strategies for integrating HLM into public healthcare, promoting health and healthspan.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"36 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477568","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":"ChatGPT-estimated occupational complexity predicts cognitive outcomes and cortical thickness above and beyond socioeconomic status among older adults","authors":"Junhong Yu, Ee-Heok Kua, Rathi Mahendran, Ted Kheng Siang Ng","doi":"10.1007/s11357-025-01570-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01570-4","url":null,"abstract":"<p>Many aging cohort studies have collected data on participants’ job titles, yet these job titles were seldom analyzed within the cognitive aging context despite their relevance to neurocognition, due to difficulties in analyzing these job titles quantitatively. While it is possible to rate these jobs’ occupational complexity (OC) using job classification systems, this can be somewhat labor-intensive and prone to human errors. To this end, we demonstrate a novel and simple method to extract OC ratings from job titles using ChatGPT. Then, we showcased the utility of these ratings in predicting cognitive and structural brain outcomes, especially compared to other socioeconomic status (SES) indicators. Community-dwelling older adults (<i>N</i> = 238, age_mean = 70) completed cognitive assessments and underwent MRI scans. Regression models were fitted to predict 14 different cognitive outcomes, vertex-wise cortical thickness (CT), and subcortical gray matter volumes, using OC scores and/or SES predictors (e.g., education, housing type, and income levels), controlling for demographical covariates. OC scores outperformed SES indicators in predicting clusters of CT increases and most cognitive outcomes, including diagnoses of mild cognitive impairment. Furthermore, OC scores significantly predicted clusters of CT increases and various cognitive outcomes, even after controlling for SES. Meta-analytic decoding suggests these clusters of CT increases occurred in regions typically associated with sensorimotor and memory processing. These results highlight the significant and unique contribution of ChatGPT-derived OC scores in predicting cognitive and brain aging outcomes. These scores are easy to derive and can be helpful in fine-tuning predictions of cognitive and brain aging outcomes.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"82 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470666","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 senolytic ABT-263 improves cognitive functions in middle-aged male, but not female, atherosclerotic LDLr−/−;hApoB100+/+ mice","authors":"Mélanie Lambert, Géraldine Miquel, Louis Villeneuve, Nathalie Thorin-Trescases, Eric Thorin","doi":"10.1007/s11357-025-01563-3","DOIUrl":"https://doi.org/10.1007/s11357-025-01563-3","url":null,"abstract":"<p>Accumulation of cerebral senescent cells may compromise the continuum between vascular and neuronal function, leading to damage and cognitive decline. Elimination of senescent cells might therefore preserve vascular and neuronal functions. To test this hypothesis, we used male and female atherosclerotic LDLr^−/−;hApoB₁₀₀^+/+ mice (ATX-mice), a model of vascular cognitive impairment (VCI), treated with the senolytic ABT-263 for 3 months (3- to 6-month or 9- to 12-month old). In young male ATX mice, prevention with ABT-263 improved spatial retention memory, in association with a higher endothelial sensitivity to shear stress and a higher hippocampal CD31⁺ endothelial cell density, lower activation of both astrocytes and glial cells. In young females, ABT-263 tended to improve delayed memory; however, atherosclerotic plaque was magnified by ABT-263, endothelial function was unaffected, hippocampal astrocyte activation increased and expression of CD31⁺ cells decreased. Hence, unlike in males, ABT-263 appears deleterious in young ATX females. In middle-aged males, the curative treatment improved the learning process and memory. Although no change in endothelial function was observed, the benefits of ABT-263 were associated with a decreased expression of several <i>inflammaging</i> markers, a higher density of CD31⁺ cells and a lower activation of glial cells. In middle-aged females, ABT-263 induced a surge of <i>inflammaging</i> markers, associated with a slower learning process. Altogether, our data demonstrate that ABT-263 differentially affects VCI, improving cognition in male while being deleterious in female ATX mice. More studies are needed to understand the mechanisms at the basis of the sexual dimorphic effects of the senolytic ABT-263.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"130 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462810","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":"International Consortium to Classify Ageing-related Pathologies (ICCARP) senescence definitions: achieving international consensus","authors":"Emma Short, Robert T. R. Huckstepp, Kambiz Alavian, Winfried M. K. Amoaku, Thomas M. Barber, Edwin J. R. van Beek, Emyr Benbow, Sunil Bhandari, Phillip Bloom, Carlo Cota, Paul Chazot, Gary Christopher, Marco Demaria, Jorge D. Erusalimsky, David A. Ferenbach, Thomas Foster, Gus Gazzard, Richard Glassock, Noordin Jamal, Raj Kalaria, Venkateswarlu Kanamarlapudi, Adnan H. Khan, Yamini Krishna, Christiaan Leeuwenburgh, Ian van der Linde, Antonello Lorenzini, Andrea Britta Maier, Reinhold J. Medina, Cecilia L. Miotto, Abhik Mukherjee, Krishna Mukkanna, James T. Murray, Alexander Nirenberg, Donald B. Palmer, Graham Pawelec, Venkat Reddy, Arianna Caroline Rosa, Andrew D. Rule, Paul G. Shiels, Carl Sheridan, Jeremy Tree, Dialechti Tsimpida, Zoe C. Venables, Jack Wellington, Stuart R. G. Calimport, Barry L. Bentley","doi":"10.1007/s11357-025-01509-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01509-9","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"65 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462811","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":"Persisting blood–brain barrier disruption following cisplatin treatment in a mouse model of chemotherapy-associated cognitive impairment","authors":"Roland Patai, Boglarka Csik, Adam Nyul-Toth, Rafal Gulej, Kiana Vali Kordestan, Siva Sai Chandragiri, Santny Shanmugarama, Stefano Tarantini, Peter Mukli, Anna Ungvari, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar","doi":"10.1007/s11357-025-01569-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01569-x","url":null,"abstract":"<p>Chemotherapy-related cognitive impairment, commonly referred to as “chemobrain,” significantly affects cancer survivors’ quality of life, yet its underlying mechanisms remain unclear. Most chemotherapeutic agents cannot cross the blood–brain barrier (BBB), yet they cause central nervous system side effects, suggesting alternative pathways of toxicity. Given that these drugs interact with the cerebrovascular endothelium at their highest concentrations, it is logical to hypothesize that endothelial damage contributes to these effects. Our recent studies demonstrated that paclitaxel-induced cognitive impairment in a mouse model results in a partial BBB disruption and subsequent neuroinflammation, mediated by chemotherapy-induced endothelial senescence. In this pilot study, we used two-photon microscopy to assess BBB permeability in mice receiving a clinically relevant cisplatin regimen, evaluating the leakage of fluorescent dextran tracers of varying molecular weights. Two months post-treatment, cisplatin-treated mice exhibited significantly increased BBB permeability to smaller molecular tracers (40 kDa, 3 kDa, and 0.3 kDa) compared to controls, indicating sustained BBB disruption. These results align with our findings for paclitaxel and suggest that chemotherapy-induced endothelial damage and senescence play a central role in cognitive impairments. Interventions targeting endothelial health could mitigate these long-term effects, improving cognitive outcomes for cancer survivors.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"2 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462797","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":"Metabolomic insight into the link of intermuscular fat with cognitive performance: the Health ABC Study","authors":"Richard Xu, Qu Tian, Megan M. Marron, Luigi Ferrucci, Shanshan Yao, Seyoung Kim, Ravi V. Shah, Venkatesh L. Murthy, Anne B. Newman, Iva Miljkovic, Caterina Rosano","doi":"10.1007/s11357-025-01559-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01559-z","url":null,"abstract":"<p>There is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging, and Body Composition Study (mean age ± SD 74.7 ± 2.9 years, 50% men, 63% white), using liquid chromatography-mass spectrometry. We confirmed that higher IMF was associated with worse DSST scores (standardized beta (95% CI) − 0.08 (− 0.12, − 0.03), <i>p</i> &lt; 0.001). Sixty-six metabolites were significantly associated with both IMF and DSST. Four of the 66 metabolites attenuated the association by ≥ 10%: higher levels of adrenic acid (polyunsaturated fatty acid), and lower levels of C20:5 lysophosphatidylcholine (lysophospholipid), 1-methylnicotinamide (vitamin B3-related myokine), and maslinic acid (triterpene) were associated with higher IMF and worse DSST. Together, they explained 41% of the IMF-DSST association. Pathway enrichment analyses identified two significant shared pathways: unsaturated fatty acid metabolism and the citrate (TCA) cycle. This study provides hypothesis-generating evidence that a set of circulating metabolites related to unsaturated fatty acids, energy metabolism, and myokines may partially explain the inverse association of IMF with processing speed. The findings, if further confirmed by independent studies, advance our understanding of molecular pathways underlying muscle-brain crosstalk. Whether the identified metabolites are early predictors of future decline in processing speed should be further investigated.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"17 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451622","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":"Transcriptomic profiling of senescence effects on blood–brain barrier-related gene expression in brain capillary endothelial cells in a mouse model of paclitaxel-induced chemobrain","authors":"Roland Patai, Tamas Kiss, Rafal Gulej, Adam Nyul-Toth, Boglarka Csik, Siva Sai Chandragiri, Santny Shanmugarama, Stefano Tarantini, Anna Ungvari, Pal Pacher, Peter Mukli, Andriy Yabluchanskiy, Anna Csiszar, Zoltan Ungvari","doi":"10.1007/s11357-025-01561-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01561-5","url":null,"abstract":"<p>Chemotherapy-induced cognitive impairment (CICI), commonly referred to as “chemobrain,” is a frequent and debilitating side effect experienced by cancer survivors treated with paclitaxel (PTX). Preclinical models have shown that PTX promotes cerebromicrovascular endothelial cell senescence, leading to chronic blood–brain barrier (BBB) disruption and neuroinflammation. Conversely, the elimination of senescent cells through senolytic therapies has been shown to restore BBB integrity, reduce neuroinflammation, and alleviate PTX-induced cognitive impairment. In this study, we tested the hypothesis that PTX-induced endothelial senescence alters gene expression patterns associated with BBB integrity. To investigate this, we analyzed a scRNA-seq dataset from the brains of mice treated with a clinically relevant PTX regimen alongside vehicle-treated control mice. We identified capillary endothelial cells by their distinct transcriptomic profiles and matched these profiles to known transcriptomic markers of cellular senescence. Our analysis confirmed that PTX induces senescence in capillary endothelial cells and revealed significant transcriptional alterations linked to impaired BBB function. In senescent endothelial cells, gene set enrichment analysis (GSEA) highlighted downregulated pathways associated with cell junction assembly and upregulated pathways involved in extracellular matrix remodeling and inflammatory signaling, including Vitronectin (VTN) and Pleiotrophin (PTN) pathways. Additionally, cell–cell communication analysis revealed reduced Junctional Adhesion Molecule (JAM) signaling, further implicating senescence in BBB disruption. These findings highlight endothelial senescence as a driver of BBB dysfunction through transcriptional changes and altered intercellular signaling. The enrichment of VTN and PTN pathways in the senescent state indicates a shift toward vascular remodeling and inflammation, exacerbating microvascular fragility and BBB disruption. Supported by prior experimental findings, this study suggests that targeting endothelial senescence and its downstream effects could mitigate PTX-induced BBB dysfunction and associated cognitive impairments. These results advance our understanding of CICI pathogenesis and provide a foundation for developing therapeutic strategies aimed at preserving vascular integrity.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"64 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451624","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}