Aging and Disease最新文献

{"title":"Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy.","authors":"YuXing Zhang, Ahmad El Hamamy, Zahid Iqbal, Arya Ranjan, Destiny Sumani, Hung Wen Lin, Louise D McCullough, Jun Li","doi":"10.14336/AD.2025.0474","DOIUrl":"https://doi.org/10.14336/AD.2025.0474","url":null,"abstract":"<p><p>Stroke is a known risk factor for dementia. Most Alzheimer's patients exhibit mixed neuropathology, with evidence of both ischemic damage and amyloid-beta (Aβ) plaque accumulation. Breathing disorders, such as apnea, are also associated with cognitive dysfunction and dementia progression. We hypothesized that stroke exacerbates respiratory dysfunction and cognitive impairment in Tg-SwDI mice, a model of cerebral amyloid angiopathy (CAA). Female CAA mice (11-13 months old) underwent permanent distal middle cerebral artery occlusion (pd-MCAO) surgery, with age- and sex-matched wild-type and sham-operated controls. Cognitive assessments included the Barnes maze, and novel object recognition test (NORT). Respiratory metrics were quantified using whole-body plethysmography, while immunohistochemistry measured Aβ deposition in the hippocampus and cortex, astrocytic markers (C3⁺GFAP⁺ for A1; S100A10⁺GFAP⁺ for A2) in the retrotrapezoid nucleus (RTN), and lymphatic vessel area (LYVE1) in deep cervical lymph nodes (dCLNs). Aβ in cerebrospinal fluid was also assessed. CAA mice without stroke exhibited higher apnea rates and impaired cognitive performance compared to wild-type controls. Stroke further increased apnea events and worsened Barnes maze escape latencies in CAA mice. Molecular analysis revealed an increase in GFAP as well as in A1 astrocytes and a reduction in A2 astrocytes in the RTN following stroke. Additionally, stroke accelerated Aβ deposition in the hippocampus and cortex while reducing Aβ clearance via cerebrospinal fluid and dCLNs. These findings suggest that stroke exacerbates respiratory dysfunction, impairs glymphatic-lymphatic clearance, and accelerates cognitive decline in CAA mice. Targeting post-stroke respiratory dysfunction may offer therapeutic potential for mitigating ischemic damage in dementia patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525988","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":"Exercise-Induced Short-Chain Fatty Acids: A Novel Therapeutic Target in Type 2 Diabetes Mellitus with Sarcopenia.","authors":"Fan Shi, Jun Chen","doi":"10.14336/AD.2025.0670","DOIUrl":"https://doi.org/10.14336/AD.2025.0670","url":null,"abstract":"<p><p>Type 2 diabetes mellitus accompanied by sarcopenia is an emerging clinical challenge in aging populations, characterized by coexisting metabolic dysfunction and the progressive loss of skeletal muscle mass and function. This comorbidity substantially elevates the risk of frailty, functional impairment, and poor clinical outcomes, highlighting the urgent need for targeted therapeutic interventions. Growing evidence suggests that gut microbiota dysbiosis contributes to the pathogenesis of both Type 2 diabetes mellitus and sarcopenia through mechanisms such as chronic inflammation, insulin resistance, and mitochondrial and autophagic dysfunction. Among gut-derived metabolites, short-chain fatty acids exert anti-inflammatory and insulin-sensitizing effects and also promote muscle metabolism and mitochondrial function. Notably, exercise increases the abundance of short-chain fatty acid-producing bacteria, thereby elevating circulating short-chain fatty acid levels and contributing to improved glucose homeostasis and skeletal muscle function. This review summarizes the effects of various exercise modalities on short-chain fatty acid production and explores the mechanisms by which short-chain fatty acids mediate the benefits of exercise in Type 2 diabetes mellitus complicated by sarcopenia, emphasizing their potential as novel therapeutic targets for integrated disease management.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525982","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":"Astrocytic Glucose Sensing Drives Synaptic Depression under Metabolic Stress.","authors":"Andrés M Baraibar, Carlos G Ardanaz, Susana Mato, Paulo Kofuji, Alfonso Araque, Maite Solas","doi":"10.14336/AD.2025.0507","DOIUrl":"https://doi.org/10.14336/AD.2025.0507","url":null,"abstract":"<p><p>Glucose is the primary energy source for the brain, and its continuous supply is essential for neuronal function. Astrocytes play a pivotal role in brain energy metabolism by mediating glucose uptake, sensing metabolic fluctuations, and modulating synaptic activity. However, astrocyte responses to transient glucose deprivation remain incompletely understood. Here, we demonstrate that astrocytic glucose uptake is crucial for network adaptation to metabolic stress. Using electrophysiology and calcium imaging approaches, we show that glucose deprivation depresses hippocampal synaptic transmission through an astrocyte-dependent mechanism that involves decreased glucose transporter 1 (GLUT1)-facilitated extracellular glucose uptake, intracellular calcium elevations, and ATP/adenosine-mediated signaling, which leads to excitatory neurotransmission depression via A1 receptors. Moreover, astrocyte-specific GLUT1 depletion prevents astrocytic responses to glucose deprivation and precludes the effects of glucose deprivation on synaptic transmission, thereby indicating that GLUT1-dependent glucose uptake is involved in astrocyte-mediated modulation of synaptic function. These findings extend the concept of astrocytic metabolic regulation beyond regions canonically classified as glucose-sensing and establish astrocytes as key integrators of energy availability and synaptic function. Our study provides new insights into the role of astrocytes in brain energy homeostasis and identifies potential therapeutic targets for metabolic disorders affecting the nervous system.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525980","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":"Dynamic CTA-Based Whole-Brain Arterial-Venous Collateral Assessment for Predicting Futile Recanalization in Acute Ischemic Stroke.","authors":"Ruoyao Cao, Yao Lu, Wei Li, Fan Yu, Shen Hu, Kunpeng Chen, Guoxuan Wang, Chengkan Sun, Qingfeng Ma, Miao Zhang, Juan Chen, Jie Lu","doi":"10.14336/AD.2025.0540","DOIUrl":"https://doi.org/10.14336/AD.2025.0540","url":null,"abstract":"<p><p>Futile recanalization is a recognized challenge in acute ischemic stroke (AIS) patients after endovascular treatment (EVT). Our purpose was to develop and validate a predictive model for futile recanalization after EVT by integrating arterial-venous collateral assessment with clinical parameters. This study included 392 AIS patients with acute anterior circulation large vessel occlusion who underwent EVT (March 2016-June 2024). Patients were stratified into training (n = 160), internal validation (n = 69), and completely independent external validation (n = 163) cohorts collected from a separate medical center. Predictors were identified using Boruta algorithm and LASSO regression. Multiple machine learning models were evaluated through discrimination, calibration, and decision curve analyses, with SHAP analysis for feature importance. Three independent predictors were identified: age (OR: 1.06, 95% CI: 1.02-1.11), whole-brain arterial collateral status (OR: 0.30, 95% CI: 0.18-0.50), and whole-brain venous collateral status (OR: 0.78, 95% CI: 0.67-0.90). The model demonstrated excellent discrimination in the training cohort (AUC: 0.914, 95% CI: 0.866-0.963), internal validation cohort (AUC: 0.918, 95% CI: 0.844-0.991), and notably maintained robust performance in the completely independent external validation cohort (AUC: 0.755, 95% CI: 0.678-0.832). Calibration plots showed good agreement between predicted and observed outcomes. SHAP analysis further confirmed the importance of arterial and venous collateral status assessments. The integration of whole-brain arterial-venous collateral assessment with clinical parameters shows potential value in predicting futile recanalization after EVT. This model, validated across multiple cohorts, may provide additional information to support clinical decision-making.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525981","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 Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.","authors":"Smijin K Soman, Micah R J Woodruff, Ruben K Dagda","doi":"10.14336/AD.2025.0440","DOIUrl":"10.14336/AD.2025.0440","url":null,"abstract":"<p><p>Mitochondria are dynamic organelles vital for neuronal function due to their ability to generate ATP, sequester cytosolic calcium (Ca²⁺), regulate lipid metabolism, and modulate apoptosis signaling. In order to maintain these essential functions in healthy neurons, mitochondria must be continuously replenished through mitochondrial turnover and biogenesis. Conversely, the dysregulation of mitochondrial homeostasis can lead to oxidative stress and contribute to the neuropathology of Parkinson's disease (PD). This review will provide an updated in-depth review of mitochondrial processes such as mitophagy, biogenesis, trafficking, oxidative phosphorylation, Ca²⁺ sequestration, mitochondrial transfer, and their relevance to PD pathophysiology. We provide an extensive overview of the neuroprotective molecular signaling pathways regulated by PD-associated proteins that converge at the mitochondrion. Importantly, in this review we highlight aspects of mitochondrial pathology that converge across multiple models including iPSCs, patient-derived fibroblasts, cell culture models, rodent models and chemical and genetic models of PD. Finally, we provide a comprehensive update on the molecular toolbox used to interrogate these signaling pathways using in vitro and in vivo models of PD and provide insight into the downstream protein targets that can be leveraged to develop novel therapies against PD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336226","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":"Updates in Intravenous Thrombolysis Treatment for Acute Ischemic Stroke in Asian Populations.","authors":"Rui Xue, Anni Wang, Ying Zhou, Min Lou","doi":"10.14336/AD.2025.0060","DOIUrl":"10.14336/AD.2025.0060","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) in Asian populations presents unique epidemiological characteristics and challenges, which are of great significance for grasping the effect of intravenous thrombolysis (IVT) in the treatment process. IVT has proven efficacy in improving outcomes for AIS patients, but its application in Asia faces distinct barriers, such as delays in diagnosis, differences in healthcare infrastructure, and variations in patient characteristics. This review examines recent research on the use of IVT for AIS in Asia, comparing findings with Western populations to identify both commonalities and disparities. We explore the current state of clinical practices, the challenges associated with treatment protocols, and the potential benefits of tailored therapeutic strategies. Additionally, the review highlights emerging trends and offers insights into how these factors may influence future research and clinical decision-making in the region.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336227","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":"Effective Therapeutic Strategies to Prevent Frailty and Falls in Community-Dwelling Older Adults.","authors":"Dmitry Tsvetkov, Marleen J Meyer-Tönnies, Mladen V Tzvetkov, Werner Weitschies, Stefan Engeli, Anna Lebedeva, Anke Hannemann, Martin C Jordan, Ulrike Garscha, Luzia Valentini, Daria Antonenko, Lieven N Kennes, Maik Gollasch","doi":"10.14336/AD.2025.0445","DOIUrl":"10.14336/AD.2025.0445","url":null,"abstract":"<p><p>Frailty and the consequent risk of falls represent significant challenges for community-dwelling older adults, often leading to severe injuries, functional decline, and loss of independence. Falls typically result from multiple interacting risk factors, many of which are modifiable through targeted interventions. This mini-review focuses on evidence from randomized controlled trials evaluating effective therapeutic strategies to prevent frailty and falls. Comprehensive assessment and management of modifiable risk factors have been shown to significantly reduce fall incidence. Key interventions include community-based and home-based exercise programs emphasizing balance and strength training. Additionally, the treatment of osteoporosis is crucial to reducing the risk of fall-related fractures. Other modifiable risk factors, such as orthostatic hypotension, polypharmacy, environmental hazards, osteoporosis, malnutrition, and cognitive impairment, require targeted assessment and intervention. Despite these advances, further research is needed to optimize multifactorial interventions and tailor strategies to individual risk profiles. Innovative research directions now span from micro to macro levels, incorporating insights from animal models to human studies, aiming to unravel underlying mechanisms and develop personalized therapeutic strategies. This review discusses emerging evidence and new interdisciplinary research avenues that offer hope for mitigating frailty and preventing falls in community-dwelling older adults.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336209","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":"Exploring the Complex Relationship between Biological Aging and Cancer in a Prospective Italian Population Cohort.","authors":"Martina Morelli, Antonietta Pepe, Simona Costanzo, Teresa Panzera, Sara Magnacca, Amalia De Curtis, Maria Loreto Muñoz Venegas, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Alessandro Gialluisi","doi":"10.14336/AD.2025.0204","DOIUrl":"10.14336/AD.2025.0204","url":null,"abstract":"<p><p>Cancer is often associated with age-related chronic conditions; however, the role of biological aging as a potential risk factor for cancer remains unclear and largely unexplored. To clarify this link, we tested the influence of two biological aging measures in an Italian prospective population cohort, the Moli-sani study (N=24,325; age ≥35 years; 51.9% women). For each participant these were based on the difference between first and a second-generation blood-based biological age estimates (BloodAge and PhenoAge) and chronological age. The resulting biological aging acceleration measures (BloodAgeAcc and PhenoAgeAcc) were tested for association with cancer mortality, first hospitalization and incident fatal/non-fatal cases, using multivariable Cox proportional hazard models. We analyzed 22,985 apparently cancer-free participants with mortality data available (median follow-up 13.1 years) and found independent increases in mortality rates per one-year increase in PhenoAgeAcc and BloodAgeAcc. Additionally, statistically significant increased risk of cancer hospitalizations was observed for PhenoAgeAcc. The analysis of incident cancers for different body sites identified both increased and decreased risks associated with biological aging acceleration. BloodAgeAcc was indeed weakly associated with a reduced risk of both breast and prostate cancer, but with an increased risk of pancreatic cancer, while PhenoAgeAcc was associated with an increased risk of lung and renal cancer. Our findings suggest that biological aging acceleration may differently impact cancer-related risks, with protective effects for some cancers versus increased risks for others. Further independent cohort studies are needed to clarify the translational clinical impact of these findings.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336113","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 Comorbidity of AD and PD: Exploring Clinical, Pathological, and Biomarker Interactions.","authors":"Qi-Lei Zhang, Yu Liu, Tian Tu, Xiao-Xin Yan","doi":"10.14336/AD.2025.0301","DOIUrl":"10.14336/AD.2025.0301","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders, primarily characterized by cognitive decline and motor dysfunction, respectively. The comorbidity of AD and PD further increases disease complexity and presents significant challenges for clinical diagnosis and treatment. Due to substantial clinical overlaps in the advanced stage of AD and PD, comorbid cases are frequently misdiagnosed as a single disease, which hinders early recognition and timely intervention. Based on pathological observations from patients with comorbidity of AD and PD, this review discusses the prevalence and clinical features of AD-PD comorbidity, the spatiotemporal progression and potential interactions of key pathological proteins, including β-amyloid (Aβ), phosphorylated tau (pTau), and α-synuclein (α-syn). The aim of this review is to update potential new insights and strategies to improve diagnostic accuracy, advance personalized therapeutic approaches, and guide future research into the underlying mechanisms of comorbidity.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336225","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":"Epigenetic Dysregulation and Osteocyte Senescence: Convergent Drivers of Osteosarcopenia in Aging Bone and Muscle.","authors":"Shahneela Nusrat, Rahman Ud Din, Muhammad Akram Tariq, Haisheng Yang","doi":"10.14336/AD.2025.0370","DOIUrl":"10.14336/AD.2025.0370","url":null,"abstract":"<p><p>Osteosarcopenia the concurrent deterioration of bone (osteoporosis) and muscle (sarcopenia) represents a critical yet understudied geriatric syndrome that synergistically amplifies frailty, fractures, and loss of independence in aging populations. This dual pathology imposes a staggering socioeconomic burden through increased disability, prolonged hospitalization, and elevated mortality. Despite its clinical urgency, therapeutic advances remain stagnant, as current interventions e.g., bisphosphonates, vitamin D supplementation are palliative and fail to address the shared molecular drivers of bone-muscle crosstalk. Emerging evidence implicates cellular senescence and epigenetic dysregulation as convergent mechanisms driving osteosarcopenia. Senescent osteocytes, burdened by oxidative stress and mitochondrial dysfunction, secrete pro-inflammatory cytokines e.g., IL-6, TNF-α and matrix-degrading enzymes (e.g., MMPs) via the senescence-associated secretory phenotype (SASP), which erodes bone integrity and propagates muscle atrophy. Simultaneously, epigenetic alterations DNA hypermethylation of osteogenic genes RUNX2, histone deacetylation repressing myogenesis MYOD1, and dysregulated non-coding RNAs (miR-133, miR-214) lock musculoskeletal tissues into a degenerative state. These processes are exacerbated by age-related inflammaging and metabolic disturbances e.g., NAD+ depletion, which amplify oxidative stress and chromatin instability. The synergy between senescence and epigenetics in perpetuating osteosarcopenia remains poorly defined. Most preclinical models overlook comorbidities (e.g., diabetes, chronic inflammation) that accelerate musculoskeletal decline. Current therapies senolytics, histone deacetylase (HDAC) inhibitors lack tissue specificity and exhibit pleiotropic effects. This review addresses these gaps by synthesizing cutting-edge insights into the senescence-epigenetics axis as a unifying driver of osteosarcopenia. By elucidating how SASP factors (e.g., myostatin) and epigenetic reprogramming e.g., sirtuin 1 (SIRT1) hypermethylation disrupt bone-muscle crosstalk, we propose novel strategies to break the self-sustaining cycle of tissue degeneration. We highlight the promise of precision geroscience leveraging CRISPR-engineered organoids, multi-omics profiling, and AI-driven biomarkers to decode tissue-specific vulnerabilities and design dual-target therapies e.g., senolytics ++ bromodomain and extra-terminal (BET) inhibitors.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336111","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}