Pub Date : 2025-12-24DOI: 10.1007/s11357-025-02060-3
Maximilian Joseph Brol, Martin Groth, Frank Erhard Uschner, Juliana Stadtmann, Tina Schomacher, Jonel Trebicka, Michael Praktiknjo, Elena Vorona
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition increasingly recognized in aging populations. However, its clinical relevance in older adults-particularly in relation to sarcopenia, cognitive function, and rehabilitation outcomes-remains poorly defined. This retrospective observational study included in-patients admitted for geriatric rehabilitation in 2022 with available abdominal ultrasound. MASLD was defined according to AASLD/EASL criteria. Demographics, comorbidities, medications, and the hepatic steatosis index were recorded. Cognitive function (MMSE, clock-drawing, GDS), hand grip strength, mobility (Tinetti, Timed Up and Go), and functional status (Barthel Index, discharge autonomy) were assessed. Analyses included regression and AUROC, with significance at p below 0.05. MASLD was present in 49.6% of the study population. No significant association was observed between MASLD and cognitive impairment. Patients with higher hand grip strengths showed higher proportions of MASLD (p = 0.01). In this cohort, hepatic steatosis index has poor capacity to detect hepatic steatosis (AUC = 0.503, 95%-CI: 0.437-0.570). Furthermore, MASLD did not predict poorer functional outcomes following the rehabilitation stay. In adjusted models, Barthel Index -but neither MASLD nor hand grip strength- was independently associated with reduced functional autonomy at discharge (p = 0.006). In elderly patients, MASLD was associated with diabetes mellitus and higher hand grip strength, while sarcopenia was linked to a lower prevalence of steatosis. MASLD showed no association with cognitive performance, functional outcomes, or prediction by the hepatic steatosis index. These findings highlight age-specific characteristics of MASLD requiring tailored clinical approaches.
{"title":"MASLD in the oldest-old: lack of association with cognition or functional autonomy and poor predictive utility of the hepatic steatosis index.","authors":"Maximilian Joseph Brol, Martin Groth, Frank Erhard Uschner, Juliana Stadtmann, Tina Schomacher, Jonel Trebicka, Michael Praktiknjo, Elena Vorona","doi":"10.1007/s11357-025-02060-3","DOIUrl":"https://doi.org/10.1007/s11357-025-02060-3","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition increasingly recognized in aging populations. However, its clinical relevance in older adults-particularly in relation to sarcopenia, cognitive function, and rehabilitation outcomes-remains poorly defined. This retrospective observational study included in-patients admitted for geriatric rehabilitation in 2022 with available abdominal ultrasound. MASLD was defined according to AASLD/EASL criteria. Demographics, comorbidities, medications, and the hepatic steatosis index were recorded. Cognitive function (MMSE, clock-drawing, GDS), hand grip strength, mobility (Tinetti, Timed Up and Go), and functional status (Barthel Index, discharge autonomy) were assessed. Analyses included regression and AUROC, with significance at p below 0.05. MASLD was present in 49.6% of the study population. No significant association was observed between MASLD and cognitive impairment. Patients with higher hand grip strengths showed higher proportions of MASLD (p = 0.01). In this cohort, hepatic steatosis index has poor capacity to detect hepatic steatosis (AUC = 0.503, 95%-CI: 0.437-0.570). Furthermore, MASLD did not predict poorer functional outcomes following the rehabilitation stay. In adjusted models, Barthel Index -but neither MASLD nor hand grip strength- was independently associated with reduced functional autonomy at discharge (p = 0.006). In elderly patients, MASLD was associated with diabetes mellitus and higher hand grip strength, while sarcopenia was linked to a lower prevalence of steatosis. MASLD showed no association with cognitive performance, functional outcomes, or prediction by the hepatic steatosis index. These findings highlight age-specific characteristics of MASLD requiring tailored clinical approaches.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819085","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}
Pub Date : 2025-12-24DOI: 10.1007/s11357-025-02067-w
Rezvan Noroozi, Aleksandra Pisarek-Pacek, Bożena Wysocka, Kamila Migacz-Gruszka, Paulina Pruszkowska-Przybylska, Magdalena Kobus, Dagmara Lisman, Julia Zacharczuk, Joanna Rudnicka, Aleksandra Iljin, Kathryn C Fitzgerald, Małgorzata Michalczyk, Piotr Kaczka, Michał Krzysztofik, Maciej Kostrzewa, Aneta Sitek, Magdalena Spólnicka, Andrzej Ossowski, Wojciech Branicki, Ewelina Pośpiech
Facial wrinkling is a prominent sign of aging, yet individuals exhibit unique trajectories of biological aging, contributing to the variability in facial appearance. Here, we present a pioneering study exploring the association between lifestyle choices, DNA methylation, and SNP genotypes with a range of facial skin aging phenotypes. The study demonstrated that age-related facial skin phenotypes are influenced by multiple environmental stressors. Epigenome-wide association analyses identified differentially methylated cytosines mapped to 151 loci, including novel genes associated with facial wrinkles, such as EDAR (cg02925966, p = 4.96 × 10-8) and NRG1 (cg26267340, p = 4.64 × 10-8), both involved in wound healing. Sensitivity analysis, conditioning on the top meQTLs, showed minor attenuation, suggesting an association independent of genetic variants. Accelerated epigenetic aging, measured in the blood of over 700 Polish individuals, was found to correlate with facial wrinkle area, photoaging, telangiectasias, and perceived facial age, with the GrimAge and FitAge clocks showing the most robust associations. Genome-wide SNP analysis identified rs73943403 (RP11-78F17.1, p = 3.72 × 10-8) associated with wrinkle area and rs113125564 (ZC3H4, p = 1.23 × 10-8) associated with perceived facial age, potentially implicating stress response and adiposity in skin aging. Finally, the study revealed the additive value of methylation and SNP data for predicting two continuous skin phenotypes, with 59.0% of the variation explained in facial wrinkle area and 26.2% in perceived facial age. The findings underscore the relevance of genetic and epigenetic factors, revealing novel candidate genes and molecular pathways involved in skin aging. These insights hold substantial translational value for dermatology, the cosmetics industry, and anti-aging strategies.
面部皱纹是衰老的显著标志，但个体表现出独特的生物衰老轨迹，导致面部外观的可变性。在这里，我们提出了一项开创性的研究，探索生活方式选择、DNA甲基化和SNP基因型与一系列面部皮肤衰老表型之间的关系。研究表明，与年龄相关的面部皮肤表型受到多种环境压力因素的影响。表观基因组关联分析鉴定了151个位点的差异甲基化胞嘧啶，包括与面部皱纹相关的新基因，如EDAR （cg02925966, p = 4.96 × 10-8）和NRG1 (cg26267340, p = 4.64 × 10-8)，它们都与伤口愈合有关。敏感性分析显示，顶部meqtl的条件作用显示出轻微的衰减，表明这种关联独立于遗传变异。研究人员对700多名波兰人的血液进行了测量，发现加速的表观遗传衰老与面部皱纹面积、光老化、毛细血管扩张和感知面部年龄有关，其中GrimAge和FitAge时钟显示出最强烈的关联。全基因组SNP分析发现，rs73943403 （RP11-78F17.1, p = 3.72 × 10-8）与皱纹面积相关，rs113125564 （ZC3H4, p = 1.23 × 10-8）与感知面部年龄相关，可能与皮肤衰老中的应激反应和肥胖有关。最后，该研究揭示了甲基化和SNP数据用于预测两种连续皮肤表型的相加值，其中59.0%的变异解释为面部皱纹面积，26.2%的变异解释为面部年龄。这些发现强调了遗传和表观遗传因素的相关性，揭示了参与皮肤衰老的新的候选基因和分子途径。这些见解对皮肤病学、化妆品行业和抗衰老策略具有重大的转化价值。
{"title":"Facial skin aging: an integrative analysis of genetics, epigenetics, and lifestyle factors.","authors":"Rezvan Noroozi, Aleksandra Pisarek-Pacek, Bożena Wysocka, Kamila Migacz-Gruszka, Paulina Pruszkowska-Przybylska, Magdalena Kobus, Dagmara Lisman, Julia Zacharczuk, Joanna Rudnicka, Aleksandra Iljin, Kathryn C Fitzgerald, Małgorzata Michalczyk, Piotr Kaczka, Michał Krzysztofik, Maciej Kostrzewa, Aneta Sitek, Magdalena Spólnicka, Andrzej Ossowski, Wojciech Branicki, Ewelina Pośpiech","doi":"10.1007/s11357-025-02067-w","DOIUrl":"https://doi.org/10.1007/s11357-025-02067-w","url":null,"abstract":"<p><p>Facial wrinkling is a prominent sign of aging, yet individuals exhibit unique trajectories of biological aging, contributing to the variability in facial appearance. Here, we present a pioneering study exploring the association between lifestyle choices, DNA methylation, and SNP genotypes with a range of facial skin aging phenotypes. The study demonstrated that age-related facial skin phenotypes are influenced by multiple environmental stressors. Epigenome-wide association analyses identified differentially methylated cytosines mapped to 151 loci, including novel genes associated with facial wrinkles, such as EDAR (cg02925966, p = 4.96 × 10<sup>-8</sup>) and NRG1 (cg26267340, p = 4.64 × 10<sup>-8</sup>), both involved in wound healing. Sensitivity analysis, conditioning on the top meQTLs, showed minor attenuation, suggesting an association independent of genetic variants. Accelerated epigenetic aging, measured in the blood of over 700 Polish individuals, was found to correlate with facial wrinkle area, photoaging, telangiectasias, and perceived facial age, with the GrimAge and FitAge clocks showing the most robust associations. Genome-wide SNP analysis identified rs73943403 (RP11-78F17.1, p = 3.72 × 10<sup>-8</sup>) associated with wrinkle area and rs113125564 (ZC3H4, p = 1.23 × 10<sup>-8</sup>) associated with perceived facial age, potentially implicating stress response and adiposity in skin aging. Finally, the study revealed the additive value of methylation and SNP data for predicting two continuous skin phenotypes, with 59.0% of the variation explained in facial wrinkle area and 26.2% in perceived facial age. The findings underscore the relevance of genetic and epigenetic factors, revealing novel candidate genes and molecular pathways involved in skin aging. These insights hold substantial translational value for dermatology, the cosmetics industry, and anti-aging strategies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819087","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}
With the aging of global populations, understanding the role of the cerebellum in aging is crucial. However, existing studies primarily focus on structural and functional changes, leaving the topological properties of cerebellar functional networks in aging unclear. Here, we explored the aging effects on the topological organization of cerebellar functional networks and investigated the relationship between these changes and cognitive function. The results revealed that, compared with young adults, older adults exhibited declines in the global and local network efficiency, modularity, and small-world properties of the cerebellum. Additionally, reductions were observed in the betweenness centrality within the visual network (VN), the nodal efficiency (NE) within the VN and lateral somatomotor network (SMN(Lat)). Moreover, the nodal local efficiency (NLE) decreased in the default mode network and SMN(Lat) of older adults. Notably, the gamma value of the cerebellar network was positively correlated with Stroop task accuracy in the incongruent condition among older adults. Additionally, aging impaired whole-brain (including cerebellar) network efficiency but preserved modularity and small-world properties, and at the nodal level, cerebellar regions showed selective reductions in NE and NLE, alongside degree centrality reorganization. Exploratory analyses revealed gender-specific patterns in cerebellar network topology during aging, with males experiencing relatively limited declines and females showing more extensive deterioration. The findings indicated that aging is associated with disruptions in the global and regional topology of the cerebellar functional connectome, with females exhibiting more pronounced deterioration than males. The integrity of cerebellar network topology appeared crucial for maintaining cognitive control.
{"title":"Age-related degradation of cerebellar functional network topology.","authors":"Mingzhu Ye,Haishuo Xia,Tao Song,Zijin Liu,Antao Chen","doi":"10.1007/s11357-025-02059-w","DOIUrl":"https://doi.org/10.1007/s11357-025-02059-w","url":null,"abstract":"With the aging of global populations, understanding the role of the cerebellum in aging is crucial. However, existing studies primarily focus on structural and functional changes, leaving the topological properties of cerebellar functional networks in aging unclear. Here, we explored the aging effects on the topological organization of cerebellar functional networks and investigated the relationship between these changes and cognitive function. The results revealed that, compared with young adults, older adults exhibited declines in the global and local network efficiency, modularity, and small-world properties of the cerebellum. Additionally, reductions were observed in the betweenness centrality within the visual network (VN), the nodal efficiency (NE) within the VN and lateral somatomotor network (SMN(Lat)). Moreover, the nodal local efficiency (NLE) decreased in the default mode network and SMN(Lat) of older adults. Notably, the gamma value of the cerebellar network was positively correlated with Stroop task accuracy in the incongruent condition among older adults. Additionally, aging impaired whole-brain (including cerebellar) network efficiency but preserved modularity and small-world properties, and at the nodal level, cerebellar regions showed selective reductions in NE and NLE, alongside degree centrality reorganization. Exploratory analyses revealed gender-specific patterns in cerebellar network topology during aging, with males experiencing relatively limited declines and females showing more extensive deterioration. The findings indicated that aging is associated with disruptions in the global and regional topology of the cerebellar functional connectome, with females exhibiting more pronounced deterioration than males. The integrity of cerebellar network topology appeared crucial for maintaining cognitive control.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"24 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808049","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}
Pub Date : 2025-12-23DOI: 10.1007/s11357-025-02057-y
Alexander Ivan B Posis,Hilary L Colbeth,Mihika S Deshpande,Kristen M George,Batool Rizvi,Rifat B Alam,Ruijia Chen,Dan M Mungas,Paola Gilsanz,María M Corrada,Rachel A Whitmer
Assessing whether grip strength is associated with cognitive decline and brain health could help identify a target to prevent or delay cognitive impairment. Therefore, we tested whether grip strength is associated with brain health as indicated by magnetic resonance imaging and domain specific cognitive decline. We also assessed whether grip strength was a cognitive resilience proxy using moderation tests. This study included cognitive and neuroimaging data from 861 participants in three harmonized cohorts. We fit multivariable linear mixed-effects and linear regression models to test associations between grip strength, neuroimaging markers, and cognition. We also tested moderation by gender and age. Greater grip strength was associated with slower verbal episodic memory decline and greater total gray matter volume. Associations of grip strength with executive function, total hippocampal volume, and white matter hyperintensities were not significant, but in the expected direction. Age moderated associations of grip strength and white matter hyperintensities. Grip strength was a significant proxy for cognitive resilience related to white matter hyperintensity volume and verbal episodic memory decline only. Future research should examine other measures of physical performance that are associated with later-life cognitive and brain health.
{"title":"Is grip strength a marker for cognitive function, neurodegeneration, and resilience?","authors":"Alexander Ivan B Posis,Hilary L Colbeth,Mihika S Deshpande,Kristen M George,Batool Rizvi,Rifat B Alam,Ruijia Chen,Dan M Mungas,Paola Gilsanz,María M Corrada,Rachel A Whitmer","doi":"10.1007/s11357-025-02057-y","DOIUrl":"https://doi.org/10.1007/s11357-025-02057-y","url":null,"abstract":"Assessing whether grip strength is associated with cognitive decline and brain health could help identify a target to prevent or delay cognitive impairment. Therefore, we tested whether grip strength is associated with brain health as indicated by magnetic resonance imaging and domain specific cognitive decline. We also assessed whether grip strength was a cognitive resilience proxy using moderation tests. This study included cognitive and neuroimaging data from 861 participants in three harmonized cohorts. We fit multivariable linear mixed-effects and linear regression models to test associations between grip strength, neuroimaging markers, and cognition. We also tested moderation by gender and age. Greater grip strength was associated with slower verbal episodic memory decline and greater total gray matter volume. Associations of grip strength with executive function, total hippocampal volume, and white matter hyperintensities were not significant, but in the expected direction. Age moderated associations of grip strength and white matter hyperintensities. Grip strength was a significant proxy for cognitive resilience related to white matter hyperintensity volume and verbal episodic memory decline only. Future research should examine other measures of physical performance that are associated with later-life cognitive and brain health.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"22 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808050","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}
Pub Date : 2025-12-22DOI: 10.1007/s11357-025-02064-z
Nishadi N Gamage,Wei-Yeh Liao,Philip J Atherton,Mathew Piasecki,George M Opie,John G Semmler
Transcranial alternating current stimulation (tACS) using a combined theta-gamma waveform can improve unilateral ballistic motor performance in the trained limb of older adults. The purpose of this study was to examine the effect of individual (theta) and combined (theta-gamma) tACS waveforms on ballistic motor performance in the trained and untrained contralateral limb (i.e. cross-limb transfer) of older adults. Sixty right-handed healthy older adults (68.9 ± 5.2 years) received either high-definition theta-gamma (6 Hz theta, 75 Hz gamma), theta (6 Hz), or sham tACS over right primary motor cortex (M1) during ballistic left-thumb abduction training for 20 min. Behavioural changes were quantified as changes in trained (left) and untrained (right) thumb acceleration. Transcranial magnetic stimulation (TMS) was used to assess changes in left and right M1 excitability, via motor-evoked potentials (MEPs) and paired-pulse short-interval intracortical inhibition (SICI). While training drove greater motor performance in both hands (all P < 0.001), theta tACS was associated with the largest improvements (P < 0.02, compared with theta-gamma and sham tACS) and was the only condition that demonstrated a post-training potentiation of MEP amplitude (P < 0.02). However, a positive relationship between performance improvement of trained and untrained hands was limited to the theta-gamma tACS condition (R2 = 0.501, P < 0.001). These results suggest that specific tACS waveforms may have unique effects on different facets of motor learning; while theta tACS can augment performance gain, theta-gamma tACS may influence cross-limb transfer of performance.
{"title":"Transcranial alternating current stimulation improves ballistic motor performance in trained and untrained limbs of healthy older adults.","authors":"Nishadi N Gamage,Wei-Yeh Liao,Philip J Atherton,Mathew Piasecki,George M Opie,John G Semmler","doi":"10.1007/s11357-025-02064-z","DOIUrl":"https://doi.org/10.1007/s11357-025-02064-z","url":null,"abstract":"Transcranial alternating current stimulation (tACS) using a combined theta-gamma waveform can improve unilateral ballistic motor performance in the trained limb of older adults. The purpose of this study was to examine the effect of individual (theta) and combined (theta-gamma) tACS waveforms on ballistic motor performance in the trained and untrained contralateral limb (i.e. cross-limb transfer) of older adults. Sixty right-handed healthy older adults (68.9 ± 5.2 years) received either high-definition theta-gamma (6 Hz theta, 75 Hz gamma), theta (6 Hz), or sham tACS over right primary motor cortex (M1) during ballistic left-thumb abduction training for 20 min. Behavioural changes were quantified as changes in trained (left) and untrained (right) thumb acceleration. Transcranial magnetic stimulation (TMS) was used to assess changes in left and right M1 excitability, via motor-evoked potentials (MEPs) and paired-pulse short-interval intracortical inhibition (SICI). While training drove greater motor performance in both hands (all P < 0.001), theta tACS was associated with the largest improvements (P < 0.02, compared with theta-gamma and sham tACS) and was the only condition that demonstrated a post-training potentiation of MEP amplitude (P < 0.02). However, a positive relationship between performance improvement of trained and untrained hands was limited to the theta-gamma tACS condition (R2 = 0.501, P < 0.001). These results suggest that specific tACS waveforms may have unique effects on different facets of motor learning; while theta tACS can augment performance gain, theta-gamma tACS may influence cross-limb transfer of performance.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"22 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801297","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}
Normal aging triggers substantial topological transformation within resting-state electroencephalography (rs-EEG) networks. Given that the small-world (SW) architecture of hemispheric EEG networks may reflect an evolutionarily and developmentally optimized organization, investigating their modulations with age offers critical insights into the dynamic reorganization of functional connectivity (FC) patterns throughout adulthood. Utilizing rs-EEG data from a single-site public repository collected under eyes-closed and eyes-open conditions, we employed graph-theory methods to delineate age-related alterations in the SW architecture of hemispheric functional networks across a broad adult age range (20-70 years). In 539 cognitively intact individuals, undirected weighted FC networks were constructed using eLORETA-based lagged linear connectivity for each hemisphere and three subnetworks: default mode network (DMN), frontal network (FN), and attentional network (AN). Further quantitative analyses revealed that age-related changes in SW metrics were observed exclusively in the right hemisphere, evident during eyes-closed rest and in network reconfiguration upon eye opening (ΔSW). Right-hemispheric SW and ΔSW showed frequency- and network-specific modulation with age: in the alpha2 band, all three subnetworks exhibited increasing trends, with U-shaped trajectories in DMN and AN and a linear rise in FN. In other frequency bands, specific SW metrics displayed an inverted-U curve relationship with age (DMN: alpha1 SW, delta ΔSW; FN: gamma SW; AN: theta, alpha1, gamma SW, theta ΔSW) in later adulthood, whereas beta2 SW and gamma ΔSW in FN decreased linearly. These findings revealed a right-lateralized pattern of age-related changes in intrinsic SW architecture and provided an eyes-state-dependent baseline for evaluating hemispheric network impairments in age-related neuropsychiatric disorders.
{"title":"Age-dependent modulations of hemispheric small-world networks in different eye states: resting-state electroencephalogram research.","authors":"Chang Xu,Chuqiao Li,Tong Cui,Shaoqi Li,Xiaodong Han,Boye Wen,Cuibai Wei","doi":"10.1007/s11357-025-02042-5","DOIUrl":"https://doi.org/10.1007/s11357-025-02042-5","url":null,"abstract":"Normal aging triggers substantial topological transformation within resting-state electroencephalography (rs-EEG) networks. Given that the small-world (SW) architecture of hemispheric EEG networks may reflect an evolutionarily and developmentally optimized organization, investigating their modulations with age offers critical insights into the dynamic reorganization of functional connectivity (FC) patterns throughout adulthood. Utilizing rs-EEG data from a single-site public repository collected under eyes-closed and eyes-open conditions, we employed graph-theory methods to delineate age-related alterations in the SW architecture of hemispheric functional networks across a broad adult age range (20-70 years). In 539 cognitively intact individuals, undirected weighted FC networks were constructed using eLORETA-based lagged linear connectivity for each hemisphere and three subnetworks: default mode network (DMN), frontal network (FN), and attentional network (AN). Further quantitative analyses revealed that age-related changes in SW metrics were observed exclusively in the right hemisphere, evident during eyes-closed rest and in network reconfiguration upon eye opening (ΔSW). Right-hemispheric SW and ΔSW showed frequency- and network-specific modulation with age: in the alpha2 band, all three subnetworks exhibited increasing trends, with U-shaped trajectories in DMN and AN and a linear rise in FN. In other frequency bands, specific SW metrics displayed an inverted-U curve relationship with age (DMN: alpha1 SW, delta ΔSW; FN: gamma SW; AN: theta, alpha1, gamma SW, theta ΔSW) in later adulthood, whereas beta2 SW and gamma ΔSW in FN decreased linearly. These findings revealed a right-lateralized pattern of age-related changes in intrinsic SW architecture and provided an eyes-state-dependent baseline for evaluating hemispheric network impairments in age-related neuropsychiatric disorders.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"41 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785817","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}
The purpose of this study was to identify the perfusion pattern of choroid plexus (CP) impairment in patients with Parkinson's disease (PD) and determine its relationship with the volume of the CP and its clinical relevance within the glymphatic system. Data from multidelayed arterial spin labeling (m-ASL), T1-weighted imaging, and diffusion tensor imaging were obtained from our consecutively enrolled patients with PD and matched healthy controls (HCs), followed by calculations of perfusion metrics, CP volume (CPV), and analysis along the perivascular space (ALPS) index and further statistical analyses. The pathological pattern of CP perfusion in PD patients included reduced cerebral blood flow (CBF) and arterial blood volume (aCBV) as well as increased CBF-arterial transit time (CBF-ATT) coupling (p < 0.05), which were significantly correlated with the CPV and ALPS indices (p < 0.05). Among the correlations with altered metrics, the linkages between CPV and perfusion metrics (CBF, aCBV, and CBF-ATT coupling) were specific to the PD group. Furthermore, the interactions between CBF and CPV and their clinical relevance to disease severity were mediated by the ALPS index (p < 0.05). These findings elucidate the diverse alterations in hemodynamics of CP and its mediating role within the glymphatic system in PD, underscoring further insights into glymphatic dynamics from the perspective of CP perfusion.
{"title":"The impaired hemodynamics of choroid plexus and its interactions within the glymphatic system in Parkinson's disease.","authors":"Song'an Shang,Shaohua Ding,Yuting Xia,Hongying Zhang,Xiang Lv,Beilei Chen,Daming Shen,Jing Ye,Yu-Chen Chen","doi":"10.1007/s11357-025-02054-1","DOIUrl":"https://doi.org/10.1007/s11357-025-02054-1","url":null,"abstract":"The purpose of this study was to identify the perfusion pattern of choroid plexus (CP) impairment in patients with Parkinson's disease (PD) and determine its relationship with the volume of the CP and its clinical relevance within the glymphatic system. Data from multidelayed arterial spin labeling (m-ASL), T1-weighted imaging, and diffusion tensor imaging were obtained from our consecutively enrolled patients with PD and matched healthy controls (HCs), followed by calculations of perfusion metrics, CP volume (CPV), and analysis along the perivascular space (ALPS) index and further statistical analyses. The pathological pattern of CP perfusion in PD patients included reduced cerebral blood flow (CBF) and arterial blood volume (aCBV) as well as increased CBF-arterial transit time (CBF-ATT) coupling (p < 0.05), which were significantly correlated with the CPV and ALPS indices (p < 0.05). Among the correlations with altered metrics, the linkages between CPV and perfusion metrics (CBF, aCBV, and CBF-ATT coupling) were specific to the PD group. Furthermore, the interactions between CBF and CPV and their clinical relevance to disease severity were mediated by the ALPS index (p < 0.05). These findings elucidate the diverse alterations in hemodynamics of CP and its mediating role within the glymphatic system in PD, underscoring further insights into glymphatic dynamics from the perspective of CP perfusion.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"6 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777401","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}
Pub Date : 2025-12-18DOI: 10.1007/s11357-025-02048-z
Brandon M Peoples,Mason C McIntosh,Kenneth D Harrison,Bria R Smith,Keven G Santamaria Guzman,Silvia E Campos-Vargas,Damaris C Cifuentes,Breanna J Mueller,Andreas N Kavazis,Darren T Beck,Michael D Roberts,Jaimie A Roper
This study aimed to assess whether dietary nitrate supplementation with resistance training (RT) augments gait performance and functional mobility in inactive middle-aged and older adults. We hypothesized that combining nitrate-rich beetroot juice (BRJ) with RT would yield improvements in gait and functional mobility compared to RT with nitrate-depleted beetroot juice placebo (PLA) supplementation. In this 12-week, randomized, double-blind, placebo-controlled pilot trial, 28 healthy, inactive adults (56 ± 7 years) were assigned to either a BRJ (~ 12.8 mmol nitrate/day) or PLA group while completing a supervised, full-body RT program (2×/week). Pre- and post-intervention assessments included the instrumented stand and walk (iSAW), 6-min walk test (i6MWT), and timed up and go (iTUG) tests. Supplement adherence, training compliance, and volume were equivalent between groups. ANCOVA analyses controlling baseline values revealed significant between-group differences favoring the BRJ group for gait speed (adjusted means: 1.38 vs 1.27 m/s, p = .010), stride length (p < .001), and iTUG duration (p < .05). Within-group analyses confirmed that the BRJ group experienced significant improvements in gait speed (p < 0.001) and iTUG duration (p < 0.05), while the PLA group showed no functional changes, indicating that 12 weeks of RT alone was insufficient to improve functional mobility in our sample despite equivalent training responses (p > .05). In our middle-aged sample, supplementing dietary nitrate alongside RT led to clinically meaningful improvements in functional mobility during self-selected conditions, exceeding the gains from 12 weeks of twice-weekly RT alone. Preliminary descriptive analyses revealed sex-specific group-level differences that might suggest emerging trends. Although no inferential statistics were conducted, the patterns provide potential directions for future research investigating the effects of RT in middle-aged adults.
本研究旨在评估膳食硝酸盐补充阻力训练（RT）是否能增强不运动的中老年成年人的步态表现和功能活动能力。我们假设将富含硝酸盐的甜菜根汁（BRJ）与RT相结合，与补充硝酸盐耗尽的甜菜根汁安慰剂（PLA）的RT相比，可以改善步态和功能活动。在这项为期12周的随机、双盲、安慰剂对照的先导试验中，28名健康、不活动的成年人（56±7岁）被分配到BRJ （~ 12.8 mmol硝酸盐/天）或PLA组，同时完成一个有监督的全身RT计划（2次/周）。干预前和干预后评估包括仪器站立和行走（iSAW）、6分钟行走测试（i6MWT）和计时起身和行走（iTUG）测试。补充剂依从性、训练依从性和量在两组之间是相等的。ANCOVA分析显示，BRJ组在步态速度方面存在显著差异（调整后均值：1.38 vs 1.27 m/s, p =）。010)，步幅（p .05）。在我们的中年样本中，在自我选择的条件下，补充膳食硝酸盐和RT导致功能活动能力有临床意义的改善，超过了12周每周两次的单独RT的收益。初步的描述性分析揭示了特定性别群体水平的差异，这可能表明了新的趋势。虽然没有进行推断统计，但这些模式为未来研究RT对中年人的影响提供了潜在的方向。
{"title":"Beyond strength: dietary nitrate augments self-selected functional mobility after resistance training in middle-aged adults.","authors":"Brandon M Peoples,Mason C McIntosh,Kenneth D Harrison,Bria R Smith,Keven G Santamaria Guzman,Silvia E Campos-Vargas,Damaris C Cifuentes,Breanna J Mueller,Andreas N Kavazis,Darren T Beck,Michael D Roberts,Jaimie A Roper","doi":"10.1007/s11357-025-02048-z","DOIUrl":"https://doi.org/10.1007/s11357-025-02048-z","url":null,"abstract":"This study aimed to assess whether dietary nitrate supplementation with resistance training (RT) augments gait performance and functional mobility in inactive middle-aged and older adults. We hypothesized that combining nitrate-rich beetroot juice (BRJ) with RT would yield improvements in gait and functional mobility compared to RT with nitrate-depleted beetroot juice placebo (PLA) supplementation. In this 12-week, randomized, double-blind, placebo-controlled pilot trial, 28 healthy, inactive adults (56 ± 7 years) were assigned to either a BRJ (~ 12.8 mmol nitrate/day) or PLA group while completing a supervised, full-body RT program (2×/week). Pre- and post-intervention assessments included the instrumented stand and walk (iSAW), 6-min walk test (i6MWT), and timed up and go (iTUG) tests. Supplement adherence, training compliance, and volume were equivalent between groups. ANCOVA analyses controlling baseline values revealed significant between-group differences favoring the BRJ group for gait speed (adjusted means: 1.38 vs 1.27 m/s, p = .010), stride length (p < .001), and iTUG duration (p < .05). Within-group analyses confirmed that the BRJ group experienced significant improvements in gait speed (p < 0.001) and iTUG duration (p < 0.05), while the PLA group showed no functional changes, indicating that 12 weeks of RT alone was insufficient to improve functional mobility in our sample despite equivalent training responses (p > .05). In our middle-aged sample, supplementing dietary nitrate alongside RT led to clinically meaningful improvements in functional mobility during self-selected conditions, exceeding the gains from 12 weeks of twice-weekly RT alone. Preliminary descriptive analyses revealed sex-specific group-level differences that might suggest emerging trends. Although no inferential statistics were conducted, the patterns provide potential directions for future research investigating the effects of RT in middle-aged adults.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"1 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771484","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}
Pub Date : 2025-12-17DOI: 10.1007/s11357-025-02029-2
Zane Koch,Jessica L Graves,Steve Annan,Phillip A Frankino,Michelle Nelson,James E McMahon,Ashley P Tovar,Hubert C Chen,Celine-Lea Halioua-Haubold,Matthew Peloquin
Aging is a complex biological process characterized by molecular changes across multiple biological scales. While these alterations have been extensively studied in humans and rodents, the molecular changes associated with aging in dogs remain underexplored despite their relevance as a model for human aging. In this study, we profiled gene expression (n = 16,273 genes) and protein abundance (n = 2041 proteins) in whole blood and blood plasma from 40 laboratory beagles across young (3-5 years old, n = 10), old (8-9 years old, n = 17), and geriatric (10-14 years old, n = 13) life stages. We identified 816 genes and 40 proteins that significantly changed in abundance during aging, converging on pathways involved in DNA repair, collagen processing, and inflammation. Notably, these canine aging signatures overlapped with human age-associated genes, including those tied to the hallmarks of aging, reinforcing the existence of conserved aging mechanisms across species.
{"title":"Multi-omic analysis of canine aging uncovers conserved aging pathways.","authors":"Zane Koch,Jessica L Graves,Steve Annan,Phillip A Frankino,Michelle Nelson,James E McMahon,Ashley P Tovar,Hubert C Chen,Celine-Lea Halioua-Haubold,Matthew Peloquin","doi":"10.1007/s11357-025-02029-2","DOIUrl":"https://doi.org/10.1007/s11357-025-02029-2","url":null,"abstract":"Aging is a complex biological process characterized by molecular changes across multiple biological scales. While these alterations have been extensively studied in humans and rodents, the molecular changes associated with aging in dogs remain underexplored despite their relevance as a model for human aging. In this study, we profiled gene expression (n = 16,273 genes) and protein abundance (n = 2041 proteins) in whole blood and blood plasma from 40 laboratory beagles across young (3-5 years old, n = 10), old (8-9 years old, n = 17), and geriatric (10-14 years old, n = 13) life stages. We identified 816 genes and 40 proteins that significantly changed in abundance during aging, converging on pathways involved in DNA repair, collagen processing, and inflammation. Notably, these canine aging signatures overlapped with human age-associated genes, including those tied to the hallmarks of aging, reinforcing the existence of conserved aging mechanisms across species.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765526","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}
Pub Date : 2025-12-17DOI: 10.1007/s11357-025-02041-6
Ji Young Kim,Taesic Lee,Sangbaek Koh
Frailty is a heightened vulnerability to physiological stressors caused by cumulative physiological decline over a lifespan. Psychological issues (depression and stress) and social problems (such as loneliness and social isolation) serve as potential risk factors for unfavorable comorbidities, including frailty, cardiometabolic disorders, and unexpected mortality. In this study, we aimed to elucidate the relationship between frailty and psychosocial factors in an aging population. The Aging-Cognition Cohort, a subset of the Wonju-Pyeongchang Arirang Cohort, included 930 participants aged 55-79 between 2020 and 2022. Participants underwent a frailty assessment based on Fried's criteria. Pearson's method-based network analysis identified key factors among five psychosocial indices (PSIs). Univariate and multivariate regression (linear and logistic methods) analyses were used to explore the relationship between frailty and the five PSIs. Network analysis revealed differential connectivity between the five PSIs and clinical biomarkers across different frailty conditions. Among psychosocial factors, the University of California Los Angeles (UCLA) Loneliness Scale emerged as a key indicator. The association of summarized values of the five PSIs (eigenvalue) and UCLA with frailty exhibited significant results independent of the covariates (eigenvalue: beta-coefficient (B) = -0.018, 95% confidence interval (CI) -0.022-0.014; UCLA: B = 0.018, 95% CI 0.012-0.024). The relationship between PSIs and frailty was maintained across all subgroup analyses. This study highlights the robust association between frailty and psychosocial factors in older Korean population.
虚弱是由于一生中累积的生理衰退而引起的生理压力的高度脆弱性。心理问题（抑郁和压力）和社会问题（如孤独和社会孤立）是不利合并症的潜在危险因素，包括虚弱、心脏代谢紊乱和意外死亡。在这项研究中，我们的目的是阐明脆弱和社会心理因素在老龄化人口之间的关系。衰老认知队列是原州-平昌阿里郎队列的一个子集，在2020年至2022年期间包括930名年龄在55-79岁之间的参与者。参与者根据弗里德的标准进行了虚弱评估。皮尔逊的基于方法的网络分析确定了五个社会心理指数（psi）中的关键因素。采用单因素和多因素回归（线性和逻辑方法）分析虚弱与五种psi之间的关系。网络分析揭示了五种psi与不同虚弱状况的临床生物标志物之间的差异连通性。在社会心理因素中，加州大学洛杉矶分校（UCLA）的孤独量表成为一个关键指标。5个psi的汇总值（特征值）和UCLA与脆弱性的相关性与协变量无关(特征值：β系数(B) = -0.018, 95%置信区间(CI) -0.022-0.014；Ucla: b = 0.018, 95% ci 0.012-0.024)。在所有亚组分析中，psi和虚弱之间的关系都保持不变。这项研究强调了韩国老年人脆弱和社会心理因素之间的强烈联系。
{"title":"The relationship between frailty status and psychosocial indices in older Korean adults.","authors":"Ji Young Kim,Taesic Lee,Sangbaek Koh","doi":"10.1007/s11357-025-02041-6","DOIUrl":"https://doi.org/10.1007/s11357-025-02041-6","url":null,"abstract":"Frailty is a heightened vulnerability to physiological stressors caused by cumulative physiological decline over a lifespan. Psychological issues (depression and stress) and social problems (such as loneliness and social isolation) serve as potential risk factors for unfavorable comorbidities, including frailty, cardiometabolic disorders, and unexpected mortality. In this study, we aimed to elucidate the relationship between frailty and psychosocial factors in an aging population. The Aging-Cognition Cohort, a subset of the Wonju-Pyeongchang Arirang Cohort, included 930 participants aged 55-79 between 2020 and 2022. Participants underwent a frailty assessment based on Fried's criteria. Pearson's method-based network analysis identified key factors among five psychosocial indices (PSIs). Univariate and multivariate regression (linear and logistic methods) analyses were used to explore the relationship between frailty and the five PSIs. Network analysis revealed differential connectivity between the five PSIs and clinical biomarkers across different frailty conditions. Among psychosocial factors, the University of California Los Angeles (UCLA) Loneliness Scale emerged as a key indicator. The association of summarized values of the five PSIs (eigenvalue) and UCLA with frailty exhibited significant results independent of the covariates (eigenvalue: beta-coefficient (B) = -0.018, 95% confidence interval (CI) -0.022-0.014; UCLA: B = 0.018, 95% CI 0.012-0.024). The relationship between PSIs and frailty was maintained across all subgroup analyses. This study highlights the robust association between frailty and psychosocial factors in older Korean population.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"147 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771485","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}
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