Aging and Disease最新文献

{"title":"Crossing Pathological Boundaries: Multi-Target Restoration of the Neurovascular Unit in Alzheimer's and Vascular Dementia-From Modern Therapeutics to Traditional Chinese Medicine.","authors":"Tengyu Zhao, Pengyu Pan, Ying Jia, Yuhan Zhou, Xinyue Zhang, Huibo Guan, Quan Li, Yanyan Zhou","doi":"10.14336/AD.2025.0801","DOIUrl":"https://doi.org/10.14336/AD.2025.0801","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and vascular dementia (VD) are the two most common forms of dementia, and they share common mechanisms, especially in regard to neurovascular dysfunction. There has been increasing evidence that the disruption of the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, neurons, and basement membrane, is one of the key early events in both AD and VD. The objective of this review is to summarize the structure and physiological function of the NVU, then discuss the pathological remodeling of the NVU in AD and VD and finally, show emerging evidence of multi-target approaches that restore the NVU and neurovascular protection. We begin with a description of the structure, and dietary regulatory roles of the NVU in cerebral homeostasis, especially related to Aβ, the blood-brain barrier (BBB), and neurovascular coupling (NVC). The NVU is then related to the pathological events that cause AD and VD, specifically to impaired Aβ clearance, inflammatory cascades, oxidative stress, and neurovascular uncoupling. Finally, the discussion focuses on a multi-target approach involving exercise, estrogen therapy, mesenchymal stem cells/exosomes, remote ischemic conditioning (RIC), and mindfulness meditation, and analyzes its implications for recovering NVU structure and function. We also discuss the concept of traditional Chinese medicine (TCM) approaches associated with NVU modulation with herbal formulas, traditional Chinese exercises and acupuncture, which has integrative pathways for MVU modulation. NVU dysfunction has a significant and converging impact on the development of both AD and VD. There is considerable support for multi-pathway neurovascular unit targeting, which should show a significant delay in cognitive decline. Incorporating multi-modal evidence from contemporary and traditional medical systems could offer new insights for individualized, neurovascular-targeted therapy for dementia.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991142","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 Risk Prediction Model for Stroke-Heart Syndrome Following Endovascular Therapy.","authors":"Lanjing Wang, Shuangfeng Huang, Yongle Wang, Omar Elmadhoun, Changhong Ren, Wenbo Zhao, Yao Yu, Guiyou Liu, Xunming Ji, Sijie Li","doi":"10.14336/AD.2025.10710","DOIUrl":"https://doi.org/10.14336/AD.2025.10710","url":null,"abstract":"<p><p>Stroke-heart syndrome (SHS) significantly impacts patient prognosis, and reperfusion treatment strategies may have an impact on the occurrence of SHS following acute ischemic stroke (AIS). This study aimed to develop a nomogram-based SHS prediction model for anterior circulation stroke patients after endovascular therapy (EVT), addressing the current gap in early risk stratification of this population. This retrospective study enrolled 218 AIS patients who underwent EVT between January 2013 and June 2021, with an observed SHS incidence of 13.8% within the first two weeks post-EVT. We used the least absolute shrinkage and selection operator regression and multivariate logistic regression analysis to identify variables strongly associated with SHS. The results showed that age (OR 1.060, 95% CI 1.021-1.100, P = 0.002), hyperlipidemia (OR 3.400, 95% CI 1.289-8.968, P = 0.013), creatinine (OR 1.023, 95% CI 1.000-1.046, P = 0.049), and total anterior circulation infarct (TACI, OR 4.875, 95% CI 1.984-11.980, P = 0.001) were significantly associated with SHS and were subsequently incorporated into the construction of a nomogram-based prediction model. The area under receiver-operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow test, and Brier score were employed to comprehensively assess the accuracy and calibration of this model. The results demonstrate that the model exhibits good discriminatory ability (AUC = 0.812), calibration (Hosmer-Lemeshow test P = 0.855, Brier score = 0.098), and robustness (internal cross-validation AUC = 0.811). Furthermore, we assessed neurological outcomes at 3 months post-stroke using the modified Rankin Scale and found that SHS was independently associated with an increased risk of unfavorable functional outcome (OR 3.267, 95% CI 1.159-9.212, P = 0.025). In conclusion, SHS significantly increases the risk of unfavorable outcomes in AIS patients undergoing EVT. The nomogram, incorporating age, hyperlipidemia, TACI, and creatinine, exhibits strong predictive accuracy for early SHS; nevertheless, multicenter prospective validation is warranted prior to clinical implementation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991123","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":"Interaction between Brain Natriuretic Peptide and QTc Prolongation on Mortality in Patients with Stroke-Heart Syndrome.","authors":"Yongle Wang, Mingyi He, Lanjing Wang, Omar Elmadhoun, Fangyan Liu, Wenbo Zhao, Changhong Ren, Yuchuan Ding, Xunming Ji, Sijie Li","doi":"10.14336/AD.2025.10711","DOIUrl":"https://doi.org/10.14336/AD.2025.10711","url":null,"abstract":"<p><p>Stroke-heart syndrome (SHS) is associated with early mortality in patients with acute ischemic stroke (AIS). However, reliable methods for timely risk stratification remain elusive. Combined monitoring of neurohormonal activation and electrocardiography may help identifying early mortality risk in SHS patients. This study investigates the interaction between elevated BNP and QTc prolongation on short-term mortality in SHS patients. This cohort study included patients with suspected AIS and concomitant SHS. SHS is defined as new-onset cardiac dysfunction after AIS, including acute coronary syndrome, heart failure, and arrhythmias. All patients underwent laboratory tests and electrocardiographic evaluations. Prolonged QTc was defined as &;gt430 milliseconds (ms) in males and &;gt450 ms in females. Patients were followed up for three months, and the study outcomes were all-cause mortality and cardiovascular and cerebrovascular disease (CCVD) mortality. Cox regression models were used to assess the relationship between BNP, QTc interval, and mortality, and the interaction between BNP and the QTc interval on mortality was analyzed. A total of 448 patients were enrolled in this analysis. Prolonged QTc was present in 217 patients (48.44%). Elevated BNP was associated with prolonged QTc (OR 1.90; 95% CI, 1.20-3.01, p=0.006). Elevated BNP, but not prolonged QTc, increased the risk of all-cause and CCVD mortality (HR 5.94; 95% CI, 1.22-29.03, p=0.028 and HR 5.48; 95% CI, 1.01-29.70, p=0.048, respectively). There was a significant interaction between elevated BNP and prolonged QTc on all-cause mortality (p for interaction &;lt0.001). Patients with prolonged QTc and higher BNP had highest risk of all-cause mortality (HR 4.92, 95% CI, 1.03-23.39, p=0.045). This study highlights a significant interaction between prolonged QTc and elevated BNP levels in predicting short-term all-cause mortality among AIS patients with SHS. Prolonged QTc emerges as a critical marker of increased mortality risk, particularly in patients with elevated BNP levels.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991153","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":"Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.","authors":"Milad Shademan, Sarah Flannery, Erik Bos, Tom M J Evers, Vahid Sheikhhassani, Alireza Mashaghi, Benno Kusters, Baziel van Engelen, Thom T Sharp, Roman Fischer, Benedikt M Kessler, Vered Raz","doi":"10.14336/AD.2025.0699","DOIUrl":"https://doi.org/10.14336/AD.2025.0699","url":null,"abstract":"<p><p>Aggregation of RNA-binding proteins (RBPs) is a hallmark of several age-related neuromuscular diseases. However, our understanding of how these aggregates drive dysfunction is often limited by the use of non-disease-relevant models. Oculopharyngeal muscular dystrophy (OPMD) is caused by a short alanine expansion mutation in the PABPN1 gene, which leads to nuclear aggregation of the protein. To investigate how these aggregates impair muscle cell function, we developed a muscle cell model with inducible expression of the pathogenic PABPN1 (A16) variant and confirmed its relevance to OPMD. Using subcellular fractionation combined with mass spectrometry and RNA sequencing, we examined the molecular consequences of nuclear PABPN1 aggregation. In the cytoplasmic fraction, we observed significant impairments in cellular metabolism and biomechanics. In the nuclear fraction, RNA metabolism was broadly disrupted, and additional RBPs were significantly enriched in insoluble aggregates. Importantly, mRNAs trapped within the aggregates were associated with impaired nuclear export and decreased translation efficiency, and the pathogenic PABPN1 variant led to reduced endogenous PABPN1 levels. Our findings support a model in which OPMD pathology arises from reduced levels of soluble PABPN1 due to nuclear aggregation and establish a mechanistic link between RBP aggregation and muscle cell dysfunction, highlighting shared pathological pathways across neuromuscular and neurodegenerative diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991101","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":"Cross-Trait Meta-Analysis Reveals a Genetic Link between Inflammation and Aging in Giant Cell Arteritis.","authors":"Laura Martínez-Gutiérrez, Inmaculada Rodriguez-Martin, Gonzalo Borrego-Yaniz, Martin Kerick, Carlo Salvarani, José Hernández-Rodríguez, María Cinta Cid, Miguel Ángel González-Gay, Ann W Morgan, Javier Martín, Lourdes Ortiz-Fernández, Ana Márquez","doi":"10.14336/AD.2025.0609","DOIUrl":"https://doi.org/10.14336/AD.2025.0609","url":null,"abstract":"<p><p>Giant cell arteritis (GCA) is a complex inflammatory disease affecting individuals over 50 suggesting a strong link with aging-related immune and vascular changes. However, the precise mechanisms underlying this age-related susceptibility remain poorly understood. Considering the relevance of aging in GCA, genetic factors influencing biological aging markers, such as telomere shortening and epigenetic age acceleration (EAA), might also contribute to its development. This study investigated the shared genetic basis between GCA and these markers to enhance understanding of the role of aging in this vasculitis. Data from approximately 6.6 million variants obtained from previously published genome-wide association studies (GWASs) of GCA (3,498 cases and 15,550 controls), telomere length (472,174 individuals), and EAA (34,710 individuals) were meta-analysed using ASSET. Significant variants (p<5×10^-8) were functionally annotated, and causal genes were prioritized using FUMA. Potential therapeutic candidates were identified through drug repurposing. This study identified 21 genetic variants shared between GCA and at least one aging marker. Two pleiotropic signals were annotated at PTPN22 and PLG, known risk factors for GCA, whereas the remainder represent potentially new susceptibility loci for this vasculitis. Several prioritized causal genes, such as SERPING1, SAR1B, SESN1, and SMC4, are involved in both inflammation and senescence, shedding light on the molecular pathways linking aging and GCA. Interestingly, expression levels of some of the prioritized genes PDE1B, ATXN2, and CNEP1R1, were dysregulated in immune cells from active patients. Drug repurposing analysis highlighted promising therapeutic candidates for GCA, including sulfasalazine, an anti-inflammatory agent, and investigational drugs targeting inflammatory pathways like NF-κB. These findings uncover significant genetic overlap between GCA and aging markers, offering insights into shared molecular pathways and potential new therapies targeting both inflammation and cellular senescence.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991108","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 Clocks Identify Harmful Epigenetic Aging Linked to Depression Severity and Cognitive Deficits in Major Depressive Disorder.","authors":"Chao Liufu, Tao Pang, Haohao Zheng, Lei Yang, Li Yang, Xuebing Huang, Ying Qian, Suhua Chang","doi":"10.14336/AD.2025.0781","DOIUrl":"https://doi.org/10.14336/AD.2025.0781","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a prevalent mental illness characterized by significant morbidity and mortality. Cognitive impairment is a common feature of MDD, closely related to the aging process. Epigenetic aging calculated using DNA methylation is an important marker of biological aging. This study aims to investigate the relationships among MDD, epigenetic aging, and cognitive function. We assessed age acceleration using epigenetic clocks based on DNA methylation data in discovery dataset with 39 MDD patients and 40 healthy controls, and then validated the results in one independent MDD cohort with 359 cases and 68 controls. The results revealed that patients with MDD exhibited significantly greater age acceleration as measured by the DamAge clock and elevated mortality risk as indicated by the Zhang clock. Notably, the age acceleration of DamAge was positively correlated with depressive symptom severity. Epigenome-wide association study of the age acceleration of DamAge identified 1,472 significant CpG sites. Enrichment analyses further revealed that these CpG sites are potentially involved in cytoskeletal mechanisms, signaling pathways, and inflammatory response. Cognitive assessments showed significant correlations between emotion recognition task performance and age acceleration from multiple epigenetic clocks, suggesting a link between accelerated epigenetic aging and cognitive impairment in MDD. Our results underscore the potential role of epigenetic aging in understanding the biological underpinnings of MDD and its associated cognitive dysfunctions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991140","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":"Decentralizing Pulmonary Screening for China's Aging Population: From Hospitals to Communities.","authors":"Leiwen Fu, Wei Shu, Yuxian Sun, Liang Li, Jian Du","doi":"10.14336/AD.2025.1027","DOIUrl":"https://doi.org/10.14336/AD.2025.1027","url":null,"abstract":"<p><p>China's aging population faces a growing burden of chronic respiratory diseases, straining the public health system. Despite the Healthy China 2030 plan's emphasis on prevention and early detection, systemic barriers, such as low public awareness, urban-rural disparities, fragmented screening models, and uneven specialist distribution, hinder effective pulmonary care for older adults. To address these challenges, a shift toward community-based strategies, including mobile low-dose CT (LDCT) screening units, is proposed. These units improve accessibility, especially in rural areas, while AI integration enhances diagnostic accuracy and telemedicine bridges specialist gaps. Strengthening local healthcare capacity through training, policy support, and coordinated care among community health stations, hospitals, and the CDC is critical. Community engagement further boosts participation and follow-up. Success will be measured by early diagnosis rates, reduced disparities, and cost-effectiveness. Aligning with Healthy China 2030, this integrated approach promises equitable, sustainable respiratory care for aging populations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991168","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":"SCAP Interacts with Trim27 to Promote Vascular Neointimal Hyperplasia by Regulating the Stability and Ubiquitination of IκBα.","authors":"Yingcheng Yao, Xing Wang, Chengcheng Xuan, Da Li, Wenqin Huang, Li Wei, Xiong Z Ruan, Danyang Li, Yaxi Chen","doi":"10.14336/AD.2025.0584","DOIUrl":"https://doi.org/10.14336/AD.2025.0584","url":null,"abstract":"<p><p>Pathological vascular remodeling and intimal hyperplasia after vascular injury are representative pathological processes in age-associated vascular diseases. Previous data from our laboratory have indicated that sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) contributes to physiological angiogenesis during embryonic development. However, the role of SCAP in neointima formation is not fully understood. Here, we aimed to explore the mechanisms of SCAP in the proliferation and migration of vascular smooth muscle cells (VSMCs) during neointima formation after injury. We utilized three types of transgenic (Tg) mice to demonstrate that SCAP participates in the regulation of injury-induced neointima formation in the vascular wall by promoting the proliferation and migration of VSMCs. This novel function of SCAP is associated with the activation of the NF-κB/MMP2/9 signaling pathway. Importantly, we reported for the first time that SCAP activates the NF-κB pathway by promoting Trim27-mediated ubiquitination of the IκBα protein and accelerating its degradation, consequently activating MMP2/9 transcription, which resulted in migration and proliferation of VSMCs. We thus propose that SCAP/IκBα/NF-κB axis is a novel signaling pathway involved in the regulation of neointimal hyperplasia, and targeting this axis may have implications for preventing neointimal hyperplasia-related diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991095","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":"Association of Unhealthy Lifestyles with Cataract Risk, and The Mediating Role of Metabolic Signature: Analysis of the UK Biobank Prospective Cohort.","authors":"Jiao Qi, Kaimeng Su, Keke Zhang, Wenwen He, Jiaqi Meng, Yu Du Md, Yi Lu, Xiangjia Zhu","doi":"10.14336/AD.2025.0522","DOIUrl":"https://doi.org/10.14336/AD.2025.0522","url":null,"abstract":"<p><p>Emerging evidence has shown an association between certain unhealthy lifestyle factors and cataract risk. However, the synergistic effect of unhealthy lifestyle factors on cataract risk and their underlying mechanisms remains unknown. This study analyzed data from 199,415 baseline cataract-free participants from the UK Biobank prospective cohort study. Multivariable Cox proportional hazards models estimated the associations of individual unhealthy lifestyle factors (smoking, alcohol consumption, physical inactivity, unhealthy diet, and high body mass index) and their synergistic effect with cataract risk. Elastic net regression was performed to identify a metabolic signature reflecting unhealthy lifestyles, and the mediation effect was evaluated. Our results showed that only smoking and physical inactivity significantly increased cataract risk. Compared to the favorable lifestyle group, the cataract risk increased by 6% in the intermediate lifestyle group (95% confidence interval [CI]: 1.02-1.09) and by 14% in the unfavorable lifestyle group (95% CI: 1.08-1.20). The Cox regression model also revealed that the metabolic signature of unhealthy lifestyles was associated with cataract risk (adjusted hazard ratio, 1.31; 95% CI: 1.18-1.45). Mediation analysis demonstrated that the metabolic signature mediated the association between unhealthy lifestyles and cataract risk, with a mediation proportion of 18.01% (95% CI: 8.57-34.70%). Metabolic pathway analysis revealed that two metabolic pathways (fatty acids and lipoprotein particle concentration and size) played a crucial mediating role. Our study underscores novel insights into the effect of unhealthy lifestyle factors on cataract risk and the mediating role of metabolic factors in this process.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793250","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":"Hip Fragility Fractures: One Or Two Pathologies? A Systematic Review and Meta-Analysis of Demographic, Diagnostic and Therapeutic Aspects.","authors":"José Luis Dinamarca-Montecinos, Miguel Yáñez, Ana Aguilera, Jean-Gabriel Minonzio","doi":"10.14336/AD.2025.0414","DOIUrl":"https://doi.org/10.14336/AD.2025.0414","url":null,"abstract":"<p><p>There is evidence that hip fragility fractures (HFF) are at least two different types of disease: intra- and extracapsular fractures (ICF and ECF). However, they are still mainly considered as one entity. Differentiating them may provide clues to improve their prevention, treatments and prognosis, and to reduce clinical, organisational and economic impacts. This work addressed published evidence about differences between ICF and ECF in older people, comparing demographic, etiologic, and therapeutic aspects, producing a summary of the state of the art, and determining which variables are associated with significant differences. A systematic review based on PRISMA methodology was conducted, searching in Google Scholar, Springer and Scopus from 01.01.1980 to 01.03.2024. Publications with p-values obtained from quantitative tests (p &;lt 0.05 statistically significant) were included. For meta-analysis, Weighted Mean Method was used. 51 studies (19 countries, 5 continents, 129,075 subjects) were included. 78.4% of main objectives was searching for differences between both HFF. 60.8% provide evidence for demographic variables; 29.4% for diagnostic variables; 11,8% for therapeutic variables. ECF occurred at an older age (p &;lt 0.05) in 43 studies (84.3%). There were no differences in sex (96.1%). 14 routine orthogeriatric blood parameters were studied. Haemoglobin, vitamin-B12, albumin and parathormone presented differences in &;gt50% of the studies. Surgical management was significantly different in all studies. Significant demographic, diagnostic and therapeutic differences exist between ICF and ECF. There is a lack of studies combining variables, especially haematological exams.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793255","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}