Aging and Disease最新文献

{"title":"Insights into Biomarkers of Alzheimer's Disease: From Core Markers to Emerging Directions.","authors":"Weiyao Zhu, Yu Wang, Ming Qin, Qinghe Zhao, Lina Feng, Mingquan Li","doi":"10.14336/AD.2025.0761","DOIUrl":"https://doi.org/10.14336/AD.2025.0761","url":null,"abstract":"<p><p>Alzheimer's disease (AD) represents a neurodegenerative condition characterized by steadily increasing prevalence and incidence, arising significant challenge to both patients and social insurance. However, the etiology of AD remains controversial so far, and pathogenesis is far more complicated. Presently, no definitive therapeutic methodologies were available for AD, and only partial symptomatic relief can be achieved. Consequently, early diagnosis and intervention are emergently needed for AD patients. The diagnostic criteria for AD are continuously evolving, and biomarker testing is becoming increasingly critical for diagnosis. Currently, the diagnosis of AD primarily relies on the detection of pathological proteins through cerebrospinal fluid (CSF) testing and positron emission tomography (PET). However, factors such as high costs, operational contraindications, and invasiveness limited the application of these technologies, making them particularly challenging to implement in large-scale clinical trials and screenings. Core fluid biomarkers for AD including β-amyloid (Aβ), phosphorylated tau protein (p-tau), total tau protein (t-tau), and their combinations were found in CSF. Although these biomarkers were demonstrated with significant specificity and sensitivity, challenges remain high concerning the collection of CSF. Blood-derived biomarkers for Aβ and tau proteins are essential for preliminary screening, diagnosis, and monitoring of AD. Additionally, other bodily fluids such as saliva, urine, and tears have been investigated for their potential as biomarkers, offering unique characteristics and applications. Emerging biomarkers, including neurofilament light chain (NfL), neurogranin (Ng), Beta-site APP cleaving enzyme 1 (BACE1), synaptosome associated protein 25 (SNAP-25), as well as inflammation-related and gene-related factors, provided valuable insights into the diagnosis and pathogenesis of AD from diverse perspectives. Despite the substantial progress made in AD biomarker research, there are still baskets of limitations concerning the complication of the disease. The current review focused on the reported literature to summarize the biomarkers associated with AD. By critically analyzing studies published over the past decade, we aimed to strengthen the recent research progress, theoretical frameworks, and unresolved challenges related to AD biomarkers.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793256","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 Cerebro-Renovascular Link: Implications of Renal Haemodynamics on Intracranial Arterial Calcification.","authors":"Joseph Amihere Ackah, Xiang-Yan Chen, Huixing Zeng, Yiming Liu, Youcheng Rong, Xuelong Li, Ben Yuk-Fai Fong, Ximin Pan, Feng Zhang, Jing Cai","doi":"10.14336/AD.2025.0489","DOIUrl":"https://doi.org/10.14336/AD.2025.0489","url":null,"abstract":"<p><p>Evidence hints that the cerebro-renovascular pathway could offer promising approaches to enhancing renal health and reducing the associated risk and burden of intracranial arterial calcification (IAC), a crucial marker for ageing-related intracranial atherosclerosis. This study explored whether renal function and renovascular haemodynamic metrics could predict the severity and load of IAC and elucidate the clinical distinctiveness between intimal and medial IAC. Seventy-seven Chinese participants were enrolled in this cross-sectional study. Kidney functions were evaluated using the estimated glomerular filtration rate (eGFR). Renovascular haemodynamics (on resistance) was assessed using duplex ultrasound to record metrics such as the resistive index (RI) of renal and interlobar arteries. Non-enhanced computed tomography (CT) assessed the count, severity, and load of IAC and classified IAC into intimal and medial. Regression models were fitted for analyses. Among 69 patients with IAC, 29% exhibited predominantly intimal and 71% predominantly medial calcification. Of those with IAC, 26 (37.7%) had an eGFR below 60 ml/min/1.73m?, 19 (27.5%) had values between 60-90 ml/min/1.73m?, and 24 (34.8%) had scores above 90 ml/min/1.73m?. Measures of eGFR &;lt60 ml/min/1.73m? were independently associated with higher renal RI [adjusted OR=3.45 (95%CI: 1.38-8.59, p=.008)]. Patients with predominantly medial IAC had higher renovascular resistance. Higher renal RI independently predicted higher IAC load [adjusted OR=1.88 (95%CI: 1.06-3.35, p=0.032)]. In summary, renovascular haemodynamics significantly determine the load and severity of IAC, particularly in individuals with reduced renal function (eGFR &;lt60 ml/min/1.73m?). The impact of renal impairment is more pronounced on medial IAC than on intimal IAC.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793254","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":"Tissue Fibrosis Decoded via Cellular Senescence: Mechanisms, Treatments, and Emerging Technologies.","authors":"Wenjie Cai, Haoyu Zhang, Zhouzhou Li, Mingyun Cai, Shiwen Yu, Peng Chen, Xinyu Song","doi":"10.14336/AD.2025.0503","DOIUrl":"https://doi.org/10.14336/AD.2025.0503","url":null,"abstract":"<p><p>Cellular senescence is one of the hallmarks of aging, and it is closely related to tissue fibrosis in various age-related diseases. By integrating multi-level and multi-dimensional data, emerging technologies can comprehensively analyze the complex mechanisms of aging and fibrosis diseases, discover new biomarkers and therapeutic targets, and promote the development of precision medicine. Most of the current reviews still focus on the molecular mechanisms of cellular senescence and fibrosis diseases, but lack a comprehensive summary of anti-aging drugs for the treatment of fibrosis-related diseases, and emerging technologies and integrated analysis of multi-omics data. This review discusses the latest evidence on the role of cellular senescence in tissue fibrosis, especially lungs, liver, and kidney fibrosis. In addition, we also introduce the application of anti-aging strategies in fibrotic diseases, especially drugs to eliminate senescent cells, and the latest application of emerging technologies in aging and fibrotic diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793259","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":"Targeting Ferroptosis to Eliminate Senescent Cells: Mechanisms and Therapeutic Potential.","authors":"Sanjay Kumar Kureel, Blake B Rasmussen","doi":"10.14336/AD.2025.0141","DOIUrl":"https://doi.org/10.14336/AD.2025.0141","url":null,"abstract":"<p><p>Cellular senescence is involved in early development, wound healing, and tumor suppression. However, the accumulation of senescent cells (SCs) drives tissue dysfunction and many age associated pathologies such as cancer and neurodegeneration. SCs demonstrate irreversible cessation of cell cycle, overexpression of anti-apodotic proteins, and senescence associated secretory phenotype (SASP), cause tissue dysfunction. Traditional senolytics induces apoptosis but have poor selectivity, uncertain long-term efficacy, and resistant SCs, limiting their use. Ferroptosis, an iron-dependent, non-apoptotic form of programmed cell death, has emerged as a promising alternative. SCs bypass the apoptosis by overexpression of an anti-apoptotic pathway, but ferroptosis uses oxidative damage to overcome these defenses, thus, making it effective for eliminating SCs. This review critically evaluates ferroptosis-mediated processes such as elevated level of iron, polyunsaturated fatty acids (PUFAs) and oxidative damages in elimination of SCs and its therapeutic potential for age related pathologies including fibrosis, cancer and neurodegenerative diseases. This review highlights the molecular mechanisms underlying ferroptosis and its potential for treating age-related diseases such as fibrosis, atherosclerosis, osteoarthritis, and neurodegeneration. By addressing the translational challenges of ferroptosis-based therapies, we emphasize its potential as a next generation senolytic for targeting senescence and aging-related pathologies.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793257","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":"Advances in the Regulation by Immune Cells of Skeletal Myositis Outcomes.","authors":"Shuxian Huang, Yongling Zhao, Yuanpeng Xin, Ziqi Yao, Yi Deng, Qihui Cai, Junyi Xie, Ruixue Wang, Zhaohong Liao","doi":"10.14336/AD.2025.0549","DOIUrl":"https://doi.org/10.14336/AD.2025.0549","url":null,"abstract":"<p><p>Skeletal myositis prevalence is increasing annually, impairing mobility and potentially causing acute organ failure. Following muscle injury, various factors within damaged muscle trigger immune cell exudation from the bloodstream to the injured area, influencing disease progression. This paper synthesizes global research on cellular/molecular mechanisms in skeletal myositis, examining immune cell regulation in exogenous-induced skeletal myositis, dystrophic myopathy, and idiopathic inflammatory myopathy (IIM). We conclude that cytokines from intramuscular immune cells represent key targets for clinical management and therapeutic development.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666790","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 Cognitive Functions Dementia Battery: A Novel Computerized Tool for Neurocognitive Disorders.","authors":"Raquel Lemos, Sofia Areias-Marques, Alexandros Lazaridis, Johanna Zils, Cristina Martins, Sílvia Almeida, Luísa Alves, David Brieber, Albino J Oliveira-Maia","doi":"10.14336/AD.2025.0412","DOIUrl":"https://doi.org/10.14336/AD.2025.0412","url":null,"abstract":"<p><p>The Cognitive Functions Dementia (CFD) is a computerized battery to assess the cognitive domains included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for neurocognitive disorders. We aimed at examining the psychometric properties and the clinical validity of the CFD for neurocognitive disorders. Psychometric characterization was conducted in healthy individuals, stratified according to age, sex, and education to represent a norming sample. Analyses included structural validity and measurement invariance, assessed through confirmatory factor analyses (CFA) and multi-group CFA, as well as internal consistency, and re-test reliability of the battery index values. Patients with major or minor neurocognitive disorder contributed data to compute receiver operating characteristics to assess diagnostic accuracy of the CFD indices relative to healthy participants. Data from 422 healthy volunteers and 81 patients were collected for the study. The confirmatory factor analysis model confirmed the validity of the structure proposed for CFD, with the five cognitive domains (attention, verbal long-term memory, expressive language, executive functions, and perceptual motor functions) describing an overall factor (CFD-Index). Good to excellent values of internal consistency and of re-test reliability were obtained for all indices. Importantly, CFD indexes were accurate in discriminating patients with neurocognitive disorders from healthy participants. The CFD battery is a valid and reliable computerized instrument to characterize patients with neurocognitive dysfunction.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666817","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":"Age-, sex-, and ancestry-specific prevalence of hearing loss in UK Biobank and All of Us Research Program.","authors":"Jun He, Sharon G Curhan, Gary C Curhan, Renato Polimanti","doi":"10.14336/AD.2025.0754","DOIUrl":"10.14336/AD.2025.0754","url":null,"abstract":"<p><p>Hearing loss (HL) is a leading cause of global disease burden, but limited information is available regarding differences among individuals of diverse ancestral backgrounds. Here, we assessed age-, sex-, and ancestry-specific prevalence of HL in 827 406 participants from UK Biobank (UKB, N = 448 193) and All of Us Research Program (AoU, N = 379 213). HL was defined based on electronic health records and self-reported information, and HL prevalence was calculated for each subgroup. Age trends and prevalence differences between sexes and ancestries were tested. Age-standardized prevalence was computed for UKB and AoU using the combined sample size of the two cohorts as the standard population. The overall HL prevalence was 28% in UKB (24% in females; 34% in males) and 16% in AoU (13% in females; 20% in males). Sex differences were statistically significant across all age groups in UKB, and among participants aged &;gt55 years in AoU. Across ancestry groups, males had a higher prevalence of HL than females, except for those of African descent in the AoU sample (10% in females and 9.5% in males). The ancestry-specific prevalence was highest among those of European descent in both UKB (29%) and AoU (20%), and lowest among those of African descent (12%) in UKB and Central/South Asian descent (7.3%) in AoU. The HL polygenic risk score was associated with HL in both female and male samples. Overall, this study provides comprehensive evidence that sex differences in HL prevalence should be considered in the context of population diversity.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666791","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":"VCAM-1 in Cognitive Impairment: Mechanisms, Biomarker Potential, and Therapeutic Targeting.","authors":"Xilong Guan, Xiaoling Zhu, Linan Zha, Wen Yu, Xiuqin Rao, Yanhong Xiong, Yu Jin, Mojiao Zhang, Tao Luo, Xiangfei Huang, Xifeng Wang, Fuzhou Hua, Jing Xu","doi":"10.14336/AD.2025.0675","DOIUrl":"https://doi.org/10.14336/AD.2025.0675","url":null,"abstract":"<p><p>Cognitive impairment (CI), a progressive decline in memory, reasoning, and executive functions, arises from neurodegenerative and cerebrovascular pathologies. Globally, 10% of adults aged ≥65 exhibit mild CI (MCI), with 15% progressing annually to dementia. Alzheimer's disease (AD) constitutes 60-70% of dementia cases, showing a higher incidence in women, while vascular dementia (VaD) accounts for 20%. By 2050, dementia cases may reach 152 million, straining healthcare systems. Vascular cell adhesion molecule 1 (VCAM-1), a key immune-inflammatory mediator, is implicated in CI pathogenesis. Expressed abundantly on endothelial cells, VCAM-1 disrupts blood-brain barrier (BBB) integrity and exacerbates neuroinflammation. This review delineates VCAM-1's role in BBB dysregulation, neuroinflammatory interactions, and its potential as a biomarker/therapeutic target. Future research should clarify VCAM-1 signaling mechanisms and develop targeted interventions for early CI management.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666819","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":"Cardiovascular Health, as per Life's Essential 8, and Impaired Lower-Extremity Function in Older Adults.","authors":"David Gómez-Ángel, Mercedes Sotos-Prieto, David Martínez-Gómez, Auxiliadora Graciani, Esther García-Esquinas, Fernando Rodríguez-Artalejo, Rosario Ortolá","doi":"10.14336/AD.2025.0347","DOIUrl":"https://doi.org/10.14336/AD.2025.0347","url":null,"abstract":"<p><p>Cardiovascular health (CVH) is a broad construct that encompasses multiple behavioral and biological factors. A decline in CVH has been associated with various adverse health outcomes, but its role in impaired lower-extremity function (ILEF), a major contributor to disability, diminished quality of life and mortality in older adults, is unknown. Therefore, we examined the cross-sectional and prospective association between CVH and lower-extremity function. Using data from 2,487 individuals aged ≥65y from the Seniors-ENRICA-2 cohort, we estimated CVH at baseline using the American Heart Association's Life's Essential 8 (LE8) score (range 0 to 100, with higher values indicating better CVH). We assessed ILEF at baseline and at 2.4-year and 5.2-year follow-ups using the Short Physical Performance Battery (SPPB). Statistical analyses were conducted with logistic regression with adjustment for the main confounders. ILEF was present in 26.8% of participants at baseline (666 events). The cumulative incidence over 2.4 and 5.2 years was 24.8% (278 events) and 22.5% (157 events), respectively. A 10-point higher LE8 score at baseline was associated with lower prevalence of ILEF (SPPB ≤9) at baseline (odds ratio [OR] 0.75, 95% confidence interval [CI]: 0.69-0.80), and lower risk of incident ILEF over 2.4 years (OR 0.77, 95% CI: 0.68-0.87) and 5.2 years (OR 0.76, 95% CI: 0.65-0.89). Physical activity, glucose levels, body mass index and nicotine exposure stood out as major contributors to the lower risk of incident ILEF associated with a higher LE8 score. A higher LE8 score was associated with both a lower prevalence and incidence of ILEF in older adults. Comprehensive evaluation of CVH offers insight into older adults' lower-extremity function and how it may progress over time, identifying opportunities for early intervention.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666792","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":"Spinal Cord Injury and Ageing: The Role of Chronic Neuroinflammation.","authors":"Tianwei Wang, Zhaoyang Zhang, Jian Liu, Liping Zhang, Qingbin Ni, Baoliang Sun, Jingyi Sun","doi":"10.14336/AD.2025.10630","DOIUrl":"https://doi.org/10.14336/AD.2025.10630","url":null,"abstract":"<p><p>As the global population ages, there is an increasing prevalence of spinal cord injury (SCI) among elderly individuals, accompanied by significant challenges in treatment and recovery. Age-related conditions, such as osteoporosis, muscle atrophy, and impaired balance, predispose older adults to falls and traumatic injuries, leading to worse neurological outcomes compared to younger patients. SCI pathophysiology consists of two phases: the initial mechanical injury and the secondary injury that involves a cascade of pathological events, including ischemia, apoptosis, and neuronal cell death. Chronic neuroinflammation has emerged as a central factor in driving long-term damage after SCI, particularly in older people, where immune senescence and a decreased ability to resolve inflammation contribute to persistent, unresolved inflammation. This prolonged inflammatory state further impedes neural regeneration and functional recovery. Aged animal models have revealed that chronic neuroinflammation is exacerbated by sustained activation of microglia and astrocytes, the infiltration of peripheral immune cells, and the secretion of pro-inflammatory cytokines, creating a pro-inflammatory microenvironment that hinders repair. Furthermore, ageing-related factors such as immunosenescence, autophagy dysfunction, and mitochondrial abnormalities exacerbate inflammation, establishing a vicious injury cycle. Despite promising studies targeting inflammation in young SCI models, there is a critical need for age-specific therapeutic approaches for elderly SCI patients. This review explores the mechanisms of chronic inflammation in aged SCI, examines key cellular mediators, and discusses potential therapeutic strategies, including pharmacological treatments, gene therapy, exosome-based interventions, and rehabilitation. Focusing on age-related differences in inflammation and healing, this work aims to provide a foundation for precision medicine tailored to the ageing population with SCI, ultimately improving clinical outcomes and quality of life for elderly patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666816","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}