GeroScience最新文献

{"title":"The influence of sensory function on walking stability in aging and falls through a head-movement perturbation model.","authors":"Eugénie Lambrecht, Elissa Embrechts, David Beckwée, Luc Vereeck, Ann Hallemans, Willem De Hertogh","doi":"10.1007/s11357-026-02602-3","DOIUrl":"https://doi.org/10.1007/s11357-026-02602-3","url":null,"abstract":"<p><p>Age-related sensory decline impairs responses to balance disturbances, increasing fall risk. Evaluating gait and balance under sensory challenges can help reveal how this decline affects instability in older adults. This study (Clinicaltrials.gov NCT06345625) incorporates head movements to evaluate the effect of sensory function - cervical sensorimotor control, vestibular function, and visual acuity - on walking stability in aging and its relationship with falls through a novel augmented-reality perturbation model. Sixty-one healthy, community-dwelling older adults (76.2 years; 40 females) with and without fall history walked with head movements (up, down, left, right) cued by augmented-reality (marker-based motion capture and headset). Additionally, cervical sensorimotor control, vestibular semicircular canals (vestibulo-ocular reflex), and static visual acuity were tested. The effects of sensory functions on mediolateral and anteroposterior margin of stability and spatiotemporal parameters (step length, width, time and gait speed) were evaluated, including moderations of fall history through linear mixed models. Older adults with poorer cervical sensorimotor control and vestibular semicircular canal function increased cautiousness in their walking pattern during head movements through increasing step width, step time, and margin of stability. Worse visual acuity was associated with decreased walking stability. Sensory function was more strongly associated with walking stability in individuals with a history of falls. The effects of head movements on walking stability were associated with sensory functioning and falls in older adults. This highlights the potential of head movements as a functional perturbation for walking stability assessments linked with age-dependent sensory decline.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224029","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":"Physical activity, sedentary behavior, sleep quality and the biological aging clocks","authors":"Jérémy Raffin,Yves Rolland,Sophie Guyonnet,Bruno Vellas,Philipe de Souto Barreto,I. H. U. HealthAge INSPIRE/Open Science study group,Lauréane Brigitte,Agathe Milhet,Elodie Paez,Emeline Muller,Sabine Le Floch,Catherine Takeda,Catherine Faisant,Françoise Lala,Gabor Abellan Van Kan,Zara Steinmeyer,Melanie Comte,Nathalie Daniaud,Fanny Boissou-Parachaud,Sandrine Andrieu,Christelle Cantet,Fabien Pillard,Bernard Teysseyre,Marie Faruch,Pierre Payoux,Catherine Takeda,Neda Tavassol,Marie Dorard,Bénédicte Razat,Camille Champigny","doi":"10.1007/s11357-026-02592-2","DOIUrl":"https://doi.org/10.1007/s11357-026-02592-2","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"52 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208768","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":"A Bacillus subtilis strain with high proficiency for biofilm formation delays the onset of aging-associated morphological defects in cholinergic neurons of C. elegans.","authors":"Weiye Gong, Josephine Priebs, Verena Alexia Ohse, Andreas Bremges, Heike Tom Dieck, Lars-Oliver Klotz, Michelle Dargatz, Holger Steinbrenner","doi":"10.1007/s11357-026-02594-0","DOIUrl":"https://doi.org/10.1007/s11357-026-02594-0","url":null,"abstract":"<p><p>Aging is accompanied by progressive functional decline and morphological defects of cholinergic neurons. Some probiotic bacteria with proficiency for biofilm formation in the gut are being discussed as potentially neuroprotective. Here, we screened Bacillus subtilis (B. subtilis) strains for biofilm production, using an in vitro assay. Thereafter, a transgenic Caenorhabditis elegans (C. elegans) strain with its cholinergic neurons expressing green fluorescent protein (GFP) was fed for up to 15 days on either the identified biofilm-producing B. subtilis strain B4U 50 or the control B. subtilis strain 168, with or without addition of a standardized Ginkgo biloba preparation. The morphology of the cholinergic neurons was monitored at several consecutive days by fluorescence microscopy. The occurrence of morphological defects such as knots and ruptures within the axons of cholinergic neurons, as observed with increasing age, was significantly lower in nematodes provided with the B4U 50 strain. Even worms whose diet was switched to B4U 50 later in life showed less damage of their neurons, as compared to worms fed on the control strain. Supplementation with the Ginkgo biloba preparation was neuroprotective in worms fed on either B. subtilis strain, while a stronger beneficial effect was observed upon combined administration of B. subtilis B4U 50 and the Ginkgo biloba preparation. In conclusion, feeding a B. subtilis strain proficient for biofilm formation, B4U 50, was neuroprotective when compared to a diet consisting of control B. subtilis, delaying the onset of aging-associated morphological defects in cholinergic neurons of C. elegans.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206824","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":"Oxidative stress-associated intestinal stem cell dysfunction during aging is attenuated by chlorogenic acid in a CncC-dependent manner.","authors":"Hyun-Jin Na, Min-Sun Kim, Mi Jeong Sung","doi":"10.1007/s11357-026-02586-0","DOIUrl":"https://doi.org/10.1007/s11357-026-02586-0","url":null,"abstract":"<p><p>Aging-associated intestinal dysfunction is characterized by impaired epithelial homeostasis, excessive intestinal stem cell (ISC) proliferation, and progressive barrier deterioration. Although oxidative stress is widely recognized as a major driver of intestinal aging, the mechanisms linking redox imbalance to ISC dysregulation remain incompletely understood. In this study, we investigated the effects of dietary chlorogenic acid (CGA) treatment using Drosophila models of physiological aging, H₂O₂-induced oxidative stress, and high-sucrose feeding. CGA treatment was associated with reduced ROS accumulation, DNA damage response, and aberrant ISC proliferation under stress conditions. Genetic analysis further demonstrated that CncC, the Drosophila ortholog of NRF2, is required for these protective effects, although our data do not establish direct activation of CncC by the parent CGA molecule or its metabolites. Transcriptomic analysis revealed CGA-associated changes in pathways related to antioxidant defense, genome maintenance, and cell cycle regulation. CGA treatment improved intestinal barrier integrity and reduced stress-associated autophagic responses. Collectively, our findings demonstrate that the intestinal protective effects observed following CGA treatment are associated with attenuation of oxidative stress and require CncC-dependent capacity. These findings extend the redox-protective effects observed following dietary CGA treatment to aging-associated ISC and epithelial homeostasis and provide a framework for further investigation of dietary bioactive compounds in aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192988","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":"A pattern to rule them all: tracing a human brain map of molecular aspects shared by Alzheimer's disease and dementia with Lewy bodies.","authors":"Riccardo Rocco Ferrari, Maria Garofalo, Rosalinda Di Gerlando, Elisa Pellegrini, Francesca Dragoni, Bartolo Rizzo, Michele Rossi, Chiara Calatozzolo, Antonio Guaita, Annalisa Davin, Stella Gagliardi, Tino Emanuele Poloni","doi":"10.1007/s11357-026-02581-5","DOIUrl":"https://doi.org/10.1007/s11357-026-02581-5","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and dementia with Lewy bodies (LBD) are the most widespread forms of degenerative dementia. However, little is known about the molecular aspects that link these conditions with each other and with aging itself. Whole transcriptome analysis and Gene Set Enrichment Analysis (GSEA) have been carried out on brain samples from hippocampus (HI), temporal and parietal cortex (TC, PC), cingulate cortex (CG), and substantia nigra (SN) of subjects with a neuropathological diagnosis of AD or LBD. According to the Abbiategrasso Brain Bank (ABB) protocol, the neuropathological diagnosis was based on a complete histological characterization, including all the main proteinopathies and vascular scoring. Transcriptomic results show major differences in the number of differentially expressed genes (DEGs) between the two pathologies. In AD, gene expression is more affected compared to LBD. DEGs have peculiar spatial distribution: HI and TC show transcriptomic changes related to synapses, while in CG, SN, and PC, changes are related to proteostasis; in LBD, DEGs are predominant in SN and PC affecting proteostasis, oxidative stress, and inflammation. In AD, GSEA shows that different regions cluster by shared biological processes. AD appears much more complex, and different forms of AD do exist. Nonetheless, the molecular signature of same regions across the two pathologies can be interestingly overlapped. Exploring the molecular processes that occur before the deposition of pathological lesions may reveal individual neurodegeneration trajectory to achieve personalized therapies, which could be much more effective than the mere immunological removal of protein deposits.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193044","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":"Streptococcus thermophilus remodels lipid metabolism to extend healthspan in Caenorhabditis elegans through NHR-49-Delta-9 desaturase axis.","authors":"Chunli Dong, Fang Liu, Xiaocong Li, Yi Xiao","doi":"10.1007/s11357-026-02603-2","DOIUrl":"https://doi.org/10.1007/s11357-026-02603-2","url":null,"abstract":"<p><p>Aging is closely associated with dysregulation of lipid metabolism, making the modulation of lipid metabolism a promising strategy for promoting healthspan. Streptococcus thermophilus, a widely utilized probiotic, has shown potential in regulating host metabolism. However, whether and how it can promote healthspan by modulating specific lipid metabolic pathways remains unclear. Using the Caenorhabditis elegans model, this study investigated the effects of Streptococcus thermophilus on healthspan and the underlying molecular mechanisms. We found that Streptococcus thermophilus supplementation significantly extended the healthspan of worms, improving multiple health indicators including enhanced motility and reduced accumulation of age pigments. Furthermore, we found that Streptococcus thermophilus remodeled the host fatty acid profile, markedly increasing the proportion of monounsaturated fatty acids (MUFAs). Mechanistically, Streptococcus thermophilus specifically upregulated the nuclear hormone receptor NHR-49 (a functional ortholog of mammalian PPARα), which in turn activated the expression of downstream delta-9 desaturase genes, including fat-5, fat-6 and fat-7, resulting in increased levels of MUFAs thereby extending healthspan. Intriguingly, exogenous supplementation of 1 mM oleic acid (OA) and palmitoleic acid (POA) restored nhr-49, fat-5, fat-6 and fat-7 mutants-induced shortened lifespan phenotype. In summary, our study demonstrates that Streptococcus thermophilus promotes healthspan by activating the NHR-49/Delta-9 desaturase axis, leading to a systemic reprogramming of lipid metabolism. This finding provides a novel mechanistic basis for developing precise probiotic-based anti-aging strategies targeting the lipid metabolic network.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193012","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":"Plasma biomarkers of neurodegeneration and physical performance in older adults.","authors":"Alice C von Alvensleben, Eunjung Kim, Tobias Kurth, Meryl S LeBoff, Amirah K Anderson, Ting Yang, Yi Ran Xu, Beth L Ostaszewski, Dennis J Selkoe, Howard D Sesso, JoAnn E Manson, Pamela M Rist","doi":"10.1007/s11357-026-02570-8","DOIUrl":"https://doi.org/10.1007/s11357-026-02570-8","url":null,"abstract":"<p><p>Physical performance declines with age, but its association with circulating neurodegeneration biomarkers remains unclear. Blood biomarkers including NT1, NfL, oAβ, and pTau217 may reflect early neurodegenerative changes linked to physical performance decline. Evidence linking these biomarkers to physical performance is limited. We analyzed older adults in the COSMOS Clinic substudy with baseline and two-year follow-up assessments of plasma NT1, NfL, and oAβ and a single assessment of pTau217. Physical performance was assessed using walking speed, grip strength, and the Short Physical Performance Battery (SPPB). The primary analysis examined associations between baseline biomarker levels and two-year changes in physical performance. Secondary analyses examined longitudinal associations between two-year changes in biomarkers and concurrent changes in physical performance. Models were adjusted for demographics, cardiovascular risk profile, body mass index, and the baseline value of the physical performance measures, and we considered all biomarkers jointly. We included 506 participants; the mean age was 69.7 years, and 49.3% were women. In the primary analysis, we found no statistically significant associations between baseline NT1, NfL, or oAβ and two-year changes in physical performance. In fully adjusted models, baseline NfL was not associated with 2-year changes in physical performance, with estimates ranging from β = -0.046 (p = 0.69) for SPPB to β = 0.350 (p = 0.48) for grip strength. Similarly, estimates for NT1 ranged from β = -0.097 (p = 0.50) for SPPB to β = 0.267 (p = 0.67) for grip strength, and those for oAβ ranged from β = -0.124 (p = 0.39) for grip strength to β = 0.008 (p = 0.25) for fast walking speed. In the secondary longitudinal analysis, two-year change in NT1 was statistically significantly associated with change in grip strength (β = 1.408, p = 0.01). No other significant associations were observed. Baseline NT1, NfL, or oAβ were not associated with changes in physical performance measures over two years. Changes in NT1 were associated with changes in grip strength. Overall, these biomarkers provided limited information on short-term physical performance decline.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181055","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":"Early cerebral hypoperfusion promotes spatially biased tau pathology in tau-seeded PS19 mice.","authors":"Shuai Zhao, Xinyi Zhang, Siyan Zhong, Kaicheng Li, Yaping Yan, Baorong Zhang, Yanxing Chen","doi":"10.1007/s11357-026-02587-z","DOIUrl":"https://doi.org/10.1007/s11357-026-02587-z","url":null,"abstract":"<p><p>Growing evidence has demonstrated a significant association between reduced cerebral blood flow and Alzheimer's disease (AD)-related cognitive impairment. Chronic cerebral hypoperfusion (CCH) has been reported to exacerbate tau hyperphosphorylation and behavioral deficits in rodents, but whether CCH promotes tau pathology at the initial stage of tauopathy remains unclear. Here we show, using a tau-seeded PS19 mouse model with unilateral common carotid artery occlusion, that early CCH exacerbates spatially biased tau pathology, inducing ipsilateral enrichment of insoluble tau in the hippocampus and, in the cortex, an ipsilateral increase that was dependent on the presence of tau seeds. Early CCH also induces myelin loss in the cortex and dorsal fornix, although no synergistic interaction was detected between tau seeds and CCH. Additionally, early CCH promotes microglial activation and IL-1β elevation, and increases hippocampal neuronal loss. In the Morris water maze, early CCH-exposed mice display a marginal trend toward reduced spatial memory performance that did not reach statistical significance. These findings indicate that early CCH facilitates tau pathology and neuroinflammation at the early stage of tauopathy, with only a marginal trend toward early cognitive changes, providing experimental evidence that vascular hypoperfusion may act as a disease modifier in the initial phase of tau pathology, with potential implications for early detection and therapeutic targeting of vascular contributions to tauopathies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180985","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":"Regional oxygen extraction fraction is higher in older adults with type 2 diabetes and obesity: associations with cognition and metabolic markers.","authors":"Mohamad N Elsharydah, Yousif Al-Khoury, Sharvinee Ragunatha Rao, Jeff Schaffert, Anujit Saha, Jack Kaufman, Ali Rezaei, Jennine Leary, Alison Jin, Jaime P Almandoz, Claudine J Gauthier, Binu P Thomas","doi":"10.1007/s11357-026-02590-4","DOIUrl":"10.1007/s11357-026-02590-4","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) and obesity are highly prevalent among older adults and associated with increased Alzheimer's disease and related dementia (ADRD) risk, but underlying mechanisms linking T2D and obesity to cognitive impairment remain partially understood. Quantitative susceptibility mapping (QSM)-derived oxygen extraction fraction (OEF) provides a noninvasive MRI-based marker of cerebral metabolism and may capture early alterations in brain physiology. In this single-center, cross-sectional pilot study, we examined QSM-derived OEF in older adults with T2D + obesity (N = 14) and age- and sex-matched controls (N = 18) and evaluated associations with blood markers and cognitive performance. Whole-brain OEF was higher in participants with T2D + obesity (29.5% vs 27.3%; p = 0.019), with higher OEF observed across all examined lobar regions (p < 0.05). The T2D + obesity group demonstrated lower Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention (p = 0.035) and Global Cognition (p = 0.022) indices and lower Delis-Kaplan Executive Function System (D-KEFS) Color-Word Switching (p = 0.001) scores. Whole-brain OEF was positively associated with leptin (p = 0.018) and negatively associated with HDL (p = 0.030). Higher regional OEF significantly correlated with lower cognitive performance, particularly D-KEFS (r = -0.40 to -0.62) and RBANS Attention (r = -0.36 to -0.41). This is the first study to support a potential link between altered cerebral oxygen extraction, metabolic dysfunction, and cognitive performance in older adults with T2D and obesity. Larger, longitudinal studies are needed to confirm these associations and determine their relevance to cognitive decline and ADRD risk.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181051","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":"Inhibition of soluble epoxide hydrolase rescues cognitive deficits by preserving neurovascular integrity and attenuating glial and neuropathology in diabetic-related dementia.","authors":"Xing Fang, Jane J Border, Huawei Zhang, Gilbert C Morgan, Andrew Gregory, Yvan Hanscom-Trofy, Rui Dong, Jun Yang, Sung Hee Hwang, Christophe Morisseau, Bruce D Hammock, Fan Fan, Richard J Roman","doi":"10.1007/s11357-026-02591-3","DOIUrl":"10.1007/s11357-026-02591-3","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a major risk factor contributing to the development of Alzheimer's disease-related dementias (ADRD). While one of the early symptoms of both Alzheimer's disease (AD) and DM-related ADRD is a reduction in cerebral blood flow, the underlying biological mechanisms driving this decline remain to be fully elucidated. Genome-wide association studies have linked AD/ADRD to single-nucleotide polymorphisms in the gene encoding soluble epoxide hydrolase (sEH), an enzyme we previously reported to be upregulated in the brains of an AD rat model. Our previous studies also demonstrated that chronic sEH inhibition with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) preserves hippocampal-dependent spatial learning and memory and improves cerebral hemodynamics in both AD and DM-ADRD models. In the present study, we found that chronic TPPU treatment (1 mg/kg/day) reduced sEH expression in the brain, improved cortical-based non-spatial recognition memory involving both cortical and hippocampal networks, and reduced anxiety in DM-ADRD rats. TPPU improved brain perfusion and normalized impaired whisker-evoked functional hyperemia, an effect associated with increased Kir2.1 expression and neurovascular coupling in cerebral capillaries. Furthermore, TPPU increased tight junction protein expression (ZO-1 and OCLN), mitigated capillary rarefaction, and suppressed astrocyte and microglial activation in DM-ADRD rats. At the cellular level, TPPU attenuated hippocampal neurodegeneration, restored the expression of synaptic proteins (PSD95 and SY38), and reduced levels of proinflammatory chemokines, including MCP-1, RANTES, and MIP-1α, in the hippocampus of DM-ADRD rats. In conclusion, TPPU preserves cognitive function in DM-ADRD by mitigating cerebrovascular dysfunction, neuroinflammation and gliosis, thereby preserving synaptic integrity and neuronal survival, and represents a promising therapeutic strategy for DM-ADRD.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181085","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}