Aging and Disease最新文献

{"title":"(Dys)regulation of the Immune System in Parkinson's Disease: Methodologies, Techniques, and Key Findings from Human Studies.","authors":"Christina M Lill, Alessia di Flora, Leonardo A Sechi, Frederico C Pereira, Nicoleta Moisoi, Neda Nikolovski, Mustafa Aktekin, Yasemin Gursoy-Ozdemir, Laura Deecke, Davide Cossu, Jan Homann, Elena R Simula, Elif Nedret Keskinoz, Devrim Oz-Arslan, Nuray Bayar Muluk, Milene Gonçalves, Elenamaria Pirovano, Cristoforo Comi, Franca Marino","doi":"10.14336/AD.2024.1163","DOIUrl":"10.14336/AD.2024.1163","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the degeneration of dopaminergic neurons in the midbrain. While PD is typically considered a disorder primarily affecting the central nervous system, there is mounting evidence of cellular dysfunction and PD pathology occurring in the peripheral nervous system, likely preceding central manifestations. In this context, it has become increasingly evident that dysregulation of both the central and the peripheral immune system plays a key role in PD pathogenesis and progression. In this narrative review, we describe and discuss the methodological approaches employed in human studies to investigate immune responses in PD pathogenesis and progression, their main findings and the potential to unveil novel therapeutic avenues. In particular, we present methodologies employed in and insights gained from human genetic studies, techniques utilized to investigate neuroinflammatory processes in post-mortem and living human brains, to investigate the blood-brain barrier, as well as the involvement of peripheral T cells and innate immune cells. Additionally, we elucidate methodologies utilized to explore the roles of mitochondrial dysfunction and infectious diseases in PD. Finally, we address the causes behind conflicting findings in the published literature, which may stem from disparities in sample ascertainment schemes, immunological protocols, and analysis designs. Given these challenges, it becomes imperative to develop methodological guidelines to enhance the validity of immunological studies in PD and facilitate their translation into clinical medicine.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245735","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":"Causality of Aging Hallmarks.","authors":"Bilu Huang, Xiaowen Hu","doi":"10.14336/AD.2025.0541","DOIUrl":"https://doi.org/10.14336/AD.2025.0541","url":null,"abstract":"<p><p>This article emphasizes the causal relationship in the mechanisms of aging, asserting that among the twelve hallmarks of aging, only telomere shortening is the cause of aging. The \"Telomere DNA and ribosomal DNA co-regulation model for cell senescence\" suggests that the shortening of telomeres and rDNA arrays can mediate various hallmarks of aging through the P53 pathway. Therefore, the best way to reverse aging and significantly extend lifespan is to increase the length of telomeres and rDNA arrays in adult stem cells within tissues.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148821","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":"Layer-Specific Colocalization of Microglia with Amyloid Plaques in the Middle Temporal Gyrus Predicts Cognitive Decline in Alzheimer's Disease.","authors":"Wellydo Kesllowd Marinho Escarião, Guilherme Henrique Viana da Silva, Hellen Suzane Clemente de Castro, Sayonara Pereira da Silva, Nelyane Nayara Martins de Santana, Ramon Hypolito Lima, Felipe Porto Fiuza","doi":"10.14336/AD.2025.0409","DOIUrl":"https://doi.org/10.14336/AD.2025.0409","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the most common form of dementia, is marked by cognitive decline and amyloid-beta (Aβ) plaque deposition in the brain. Microglia cluster around Aβ plaques shifting to a plaque-associated microglia (PAM) immunophenotype. This study investigates the association between Aβ, microglia and PAM with cognitive performance in 75 older adults, 39 with normal cognition and 36 with AD. Postmortem brain samples containing the middle temporal gyrus (MTG) underwent duplex immunohistochemistry for ionized calcium-binding adaptor molecule 1 (IBA1) and Aβ. A machine learning pipeline quantified parameters of Aβ, microglia and PAM expression. This study evaluated sex- and layer-specific patterns of expression of these parameters and the relationship with global cognitive performance, as measured by the Cognitive Abilities Screening Instrument (CASI) and the Mini-Mental State Examination (MMSE). Additionally, four specific cognitive domains, memory, executive function, language, and visuospatial processing, were evaluated. Aβ and PAM were significantly higher in AD, with no sex- or layer-specific differences. In layers 3 and 4, Aβ plaque size was inversely correlated with MMSE. In all layers, total and activated microglial densities were related to executive function, but in a cognitive status-dependent manner. In layers 5 and 6, higher PAM expression correlated with lower CASI and MMSE scores. PAM expressions in layers 3, 5, and 6 were negatively associated with memory scores. This study characterizes Aβ, microglia, and PAM patterns in the MTG, revealing layer-specific associations between histopathological metrics and cognitive domains. It also highlights PAM as a potential therapeutic target to mitigate cognitive decline in AD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148828","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":"Spatial Insights in Cardiovascular Aging.","authors":"Zhongling Dai, Huiqin Ding, Quan Zhang, Liyao Fu, Shi Tai","doi":"10.14336/AD.2025.0272","DOIUrl":"https://doi.org/10.14336/AD.2025.0272","url":null,"abstract":"<p><p>Spatial omics provides unprecedented insights into how the cardiovascular system is spatially organized and how cellular phenotypes are distributed. Researchers have been able to clarify the complex spatial architecture of the cardiovascular system and how cellular phenotypes are distributed during the aging process by integrating data from spatial omics. In addition, this new technology has revealed previously hidden patterns of gene expression and cellular communication that were not detected using traditional bulk omics approaches. In this review, we explore the contribution of spatial omics in clarifying the molecular mechanisms that influence cardiovascular aging, highlighting the importance and application of spatial omics in unraveling the spatial heterogeneity within the aging cardiovascular system. This will help us understand the molecular mechanisms implicated in age-related cardiovascular diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148757","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":"Anillin Recedes in p53-Dependent Senescence of Tumor Cells and Reappears in Cells Escaping from Senescence.","authors":"Tomasz Buko, Karolina Staniak, Magdalena Dudkowska, Dorota Janiszewska, Dominika Dębowska, Agnieszka Gadecka, Anna Bielak-Zmijewska","doi":"10.14336/AD.2025.0402","DOIUrl":"https://doi.org/10.14336/AD.2025.0402","url":null,"abstract":"<p><p>Anillin is a protein whose most recognizable function is coordinating the spatial distribution of cytoskeletal proteins during the course of cytokinesis. Its level increases in many types of cancer, and therefore, it has been proposed as a prognostic marker for some of them. Anillin is detected in the cell nucleus but so far, its nuclear role has not been recognized. Our recent studies have shown that anillin gene expression and protein level decrease in normal senescent cells, which could be attributed to inhibition of proliferation. However, its presence in the nucleus of neurons, postmitotic cells, suggests functions other than regulation of cytokinesis. Some data indicate that anillin expression may be regulated by p53, a protein usually induced in cells undergoing senescence due to various stimuli. The presence of p53 binding sites in the upstream promoter region of the anillin gene was mainly shown in in silico studies, and, so far, few experimental data seem to confirm such regulation. This study aimed to test whether anillin level decreases in senescent cancer cells and whether this is due to regulation by p53. Using p53-proficient and p53-deficient cancer cells, we have shown that anillin levels decreased in cells whose senescence was p53-dependent. We also showed that in cells escaping senescence, anillin reappeared with proliferation resumption, which correlated with decreased p53 levels. Our results demonstrate the universality of anillin reduction during the course of senescence and show that p53 is a negative regulator of this protein.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148818","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":"Postbiotic Parabacteroides Distasonis Supplementation Enhances Intestinal and Skeletal Muscle Function in Aged Mice.","authors":"Pablo Morgado-Cáceres, Hernán Huerta, Cristian Bergman, Reinaldo Figueroa, Paula Farias, Gabriel Quiroz, Ute Woehlbier, Karen Mella, Osmán Díaz-Rivera, Sergio Linsambarth, Paulina Calderón-Romero, Felipe A Court, Denisse Sepulveda, Daniela Sauma, Patricia Luz-Crawford, Anibal A Vargas, Catalina Gonzalez-Seguel, J César Cárdenas, Alenka Lovy","doi":"10.14336/AD.2025.0188","DOIUrl":"https://doi.org/10.14336/AD.2025.0188","url":null,"abstract":"<p><p>Parabacteroides distasonis (Pd), a core member of the human gut microbiota, is enriched in centenarians, suggesting a potential role in promoting organismal resilience. While Pd supplementation has been shown to alleviate cancer and inflammatory diseases, its ability to mitigate the decline associated with aging remains unexplored. Here, we demonstrate that postbiotic Pd supplementation induces multiple beneficial effects in 18- and 26-month-old mice following three months of treatment. Pd-treated mice exhibit lower blood glucose levels and increased ketone body production. In the gut, Pd reduces colon shortening observed in aged control mice and decreases the inflammatory mediator NFκB, in the colonic mucosa. Microbiome analysis further reveals enhanced gut microbiota diversity in Pd-supplemented mice. Additionally, FITC-dextran permeability assays indicate improved intestinal barrier function. Cell culture experiments in HCT116 colon cell line show that Pd reduces oxygen consumption and promotes mitochondrial networking, accompanied by upregulation of PGC1α and CHOP, suggesting a mitohormetic response. Beyond metabolic and gut-related benefits, Pd supplementation enhances skeletal muscle strength in both 18- and 26-month-old mice. Proteomic analysis of gastrocnemius muscle reveals that Pd increases the expression of mitochondrial proteins associated with mitochondrial fitness and survival. Notably, Pd-supplemented mice challenged with a high-fat diet gain weight at a slower rate, while maintaining better skeletal muscle coordination and strength. In summary, our findings suggest that postbiotic Pd supplementation enhances metabolic health, reduces inflammation, improves mitochondrial function, and preserves muscle strength in aged mice. These results position Pd as a promising therapeutic tool for promoting healthy aging and combating aging-related diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148755","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":"Associations of Elevated Red Cell Distribution Width (RDW) with Decreased Physical and Cognitive Function in Older Adults, and The Potential Mediation by Mitochondrial Energetics: The Study of Muscle, Mobility and Aging (SOMMA).","authors":"Kyoung Min Kim, Li-Yung Lui, Theresa Mau, Paul M Coen, Steven R Cummings","doi":"10.14336/AD.202","DOIUrl":"https://doi.org/10.14336/AD.202","url":null,"abstract":"<p><p>We analyzed the association between RDW and skeletal muscle mitochondrial energetics and how skeletal muscle mitochondrial energetics may mediate the associations of RDW with physical and cognitive performance. The study analyzed cross-sectional baseline data from the Study of Muscle, Mobility and Aging (SOMMA) that enrolled 864 participants aged 70 and older (mean=76.3 years). RDW, clinical and demographic parameters were assessed. Comprehensive evaluations were conducted for both physical and cognitive function using objective and subjective measures. Elevated RDW values were significantly correlated with decreased physical performance, evidenced by reduced cardiorespiratory fitness (VO2peak) and longer time to 400 m Walk, alongside impaired cognitive performance. Higher RDW values also demonstrated robust negative associations with various measurements of mitochondrial energetics, including maximal ATP production and oxidative phosphorylation. Mediation analysis revealed that impaired mitochondrial function partly mediated the associations between RDW values and VO2peak, and other physical and cognitive performance. These findings suggest that higher RDW is associated with declines in various physical and cognitive performance, with skeletal muscle mitochondrial energetics serving as a potential mediating factor. Causal inferences about potential mediation are limited by the cross-sectional design of the study. Nevertheless, the findings highlight the value of RDW as a potential biomarker for age-related declines in physical and cognitive function partly mediated by mitochondrial energetics.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148819","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":"Tumor Immunosenescence Driven by Chronic Inflammation: Mechanisms, Microenvironment Remodeling and Therapeutic Strategies.","authors":"Yiran Liu, Yang Yu, Yuanyuan Chen, Jing Zhuang, Changgang Sun","doi":"10.14336/AD.2025.0471","DOIUrl":"https://doi.org/10.14336/AD.2025.0471","url":null,"abstract":"<p><p>The development of malignant tumors, as one of the most challenging public health issues today, is closely related to the interaction of chronic inflammation and immunosenescence. This review systematically analyzes the multidimensional mechanism of chronic inflammation driving immunosenescence. Chronic inflammation triggers immunosuppression and drives immunosenescence through interactions with inflammatory signals, the senescence-associated secretory phenotype (SASP), metabolic reprogramming, and microbiome. These processes remodel the tumor microenvironment via a multidimensional interaction network, which significantly weakens the anti-tumor immune response and accelerates tumor progression. This review proposes targeting strategies focusing on source intervention, SASP network blockade, and combination therapy optimization, as well as precise regulation with the help of novel technologies to break through the limitations of traditional immune checkpoint inhibition and provide new breakthroughs for overcoming tumor immune escape.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148758","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":"Gut Fungi in Alzheimer's Disease: Mechanisms, Biomarkers and Therapeutic Potential.","authors":"Ziyu Liu, Zhuo Chen, Xiaoyan Zhang, Yi Ge, Duo Yuan, Huihong Zhai","doi":"10.14336/AD.2024.1310","DOIUrl":"https://doi.org/10.14336/AD.2024.1310","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder of aging that imposes a heavy medical and socioeconomic burden. Its multifactorial pathology-including amyloid-β (Aβ) accumulation, tauopathy, and chronic neuroinflammation-lacks effective disease-modifying treatments. Recent studies highlight the gut-brain axis, specifically the intestinal mycobiome (fungal community), as a novel factor in AD. In this review, we summarize evidence on gut fungi in AD. Altered gut fungal profiles have been reported in AD patients, including enrichment of Candida tropicalis and Schizophyllum commune and reduction of Rhodotorula mucilaginosa, and in AD mouse models, such as increased abundance of the Dipodascaceae family. Fungi can translocate or release bioactive molecules that impact the brain; for instance, fungal proteins (enolase, β-tubulin) and polysaccharides (chitin) have been detected in AD brain tissue. Fungal metabolites also emerge as potential biomarkers; notably, plasma sterigmatocystin levels were significantly higher in AD patients compared to controls. Mechanistically, gut fungi (such as Candida or Malassezia species) may activate microglia and promote Aβ deposition via inflammatory pathways, while fungal prion-like proteins can accelerate AD protein aggregation in vitro. Conversely, certain fungi exert neuroprotective effects; oral administration of the probiotic yeast Saccharomyces boulardii attenuated cognitive deficits and Aβ pathology in APP/PS1 mice. Importantly, fecal fungal profiling is non-invasive and may serve as a practical AD screening tool. Collectively, these findings nominate gut fungi as potential biomarkers and therapeutic targets. Future work should validate specific mycobiome signatures and develop fungus-targeted interventions to enable earlier diagnosis and novel treatments for AD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148824","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":"Microglial Histaminergic Signaling Promotes Interleukin-10 Production and Ameliorates Motor Dysfunction in Parkinson's Disease.","authors":"Yining Wang, Minglai Zhao, Lingjuan Li, Xiaoying Liu, Liqin Lang, Xin Zhang, Zengxin Qi","doi":"10.14336/AD.2025.0088","DOIUrl":"https://doi.org/10.14336/AD.2025.0088","url":null,"abstract":"<p><p>Histamine functions as a neurotransmitter regulating multiple neural processes, whereas interleukin-10 (IL-10) is an anti-inflammatory cytokine with recognized neuroprotective properties. Previous research suggests that histamine can stimulate the release of various inflammatory mediators, including IL-10. However, the precise molecular mechanisms governing the interaction between histamine and IL-10, particularly their role in safeguarding dopaminergic neurons in Parkinson's disease (PD), have not been fully elucidated. The current findings suggest that, within the context of PD, histamine levels are elevated in the substantia nigra pars compacta (SNc) microglia, leading to an upregulation of IL-10 expression through activation of the H2 receptor and the downstream cAMP/PKA/p38β/CREB signaling cascade. However, the increased histamine concentration was negatively regulated by the IL-10 expression, allowing a limited increase in its concentration. Furthermore, the H2R-IL-10 pathway activation inhibited microglial activation and the production of inflammatory factors. Moreover, the H2R-IL-10 signaling axis modulated both membrane resistance and the expression of cleaved caspase-3 mRNA in dopaminergic neurons, contributing to the improvement of motor deficits in LPS-induced mouse models. These observations suggest that, in the pathological context of PD, microglia in the SNc exhibit increased production of histamine and IL-10 in a mutually regulatory manner. Elevated histamine levels further enhance IL-10 expression, which confers neuroprotection to dopaminergic neurons through its anti-inflammatory actions, ultimately alleviating motor impairments associated with PD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148754","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}