IF 6

npj aging Pub Date : 2026-05-09 DOI: 10.1038/s41514-026-00400-x

Zhi Li, Chengzhe Tao, Ziyi Zhou, Michael N Pollak, Edward L Giovannucci, Mingyang Song

引用次数: 0

Modifiable risk factors attenuated longevity genetic predisposition on life expectancy in the oldest old. 可改变的风险因素降低了长寿遗传倾向对老年人预期寿命的影响。

IF 6

npj aging Pub Date : 2026-05-05 DOI: 10.1038/s41514-026-00393-7

Shimin Chen, Ke Han, Shengshu Wang, Shanshan Yang, Yueting Shi, Wenchang Wang, Shengyan Du, Xiaoxin Ye, Yanhao Wan, Jianhua Wang, Miao Liu, Yao He

{"title":"Modifiable risk factors attenuated longevity genetic predisposition on life expectancy in the oldest old.","authors":"Shimin Chen, Ke Han, Shengshu Wang, Shanshan Yang, Yueting Shi, Wenchang Wang, Shengyan Du, Xiaoxin Ye, Yanhao Wan, Jianhua Wang, Miao Liu, Yao He","doi":"10.1038/s41514-026-00393-7","DOIUrl":"https://doi.org/10.1038/s41514-026-00393-7","url":null,"abstract":"In this prospective cohort study of 1545 participants aged 80 years and older from the China Hainan Centenarian Cohort Study, we investigated the independent and joint associations of modifiable risk factors and genetic predisposition with life expectancy. A weighted modifiable risk factor score (MRFS) based on 11 factors and a polygenic risk score (PRS) for longevity were constructed. A favorable modifiable risk factor profile (low MRFS) was associated with a 40.7% lower death risk (HR 0.593, 95%CI 0.505-0.696) compared with high MRFS. Genetic predisposition to longer lifespan (high PRS) conferred a 13.0% lower risk (HR 0.870, 95%CI 0.768-0.986). Participants with both low MRFS and high PRS had the lowest mortality (HR 0.544, 95%CI 0.432-0.686), with a borderline significant multiplicative interaction (P = 0.040). Life expectancy gains from a low MRFS were more pronounced in those with high PRS (6.92 years at age 80) than low PRS (5.35 years). Among the oldest-old Han Chinese, favorable modifiable risk profiles and genetic predisposition independently and jointly contribute to substantially longer life expectancy. Importantly, an unfavorable modifiable profile may largely negate genetic longevity benefits, emphasizing the critical role of managing these factors even in advanced age and irrespective of genetic inheritance.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

D-pinitol extends the lifespan of Caenorhabditis elegans through integrated antioxidant defense, proteostasis, and autophagy signaling. d -蒎醇通过综合抗氧化防御、蛋白质平衡和自噬信号延长秀丽隐杆线虫的寿命。

IF 6

npj aging Pub Date : 2026-04-27 DOI: 10.1038/s41514-026-00381-x

Lin Shi, Yu-Long Liu, Meng-Ni Dai, Ya-Xuan Ma, Jia-Ning Wu, Le Guo, Lei Luo, Hui-Hui Fu, Chen-Yan Huang, Jing-Yi Zhang, Yi-Nuo Kou, Huai-Rong Luo, Gui-Sheng Wu

{"title":"D-pinitol extends the lifespan of Caenorhabditis elegans through integrated antioxidant defense, proteostasis, and autophagy signaling.","authors":"Lin Shi, Yu-Long Liu, Meng-Ni Dai, Ya-Xuan Ma, Jia-Ning Wu, Le Guo, Lei Luo, Hui-Hui Fu, Chen-Yan Huang, Jing-Yi Zhang, Yi-Nuo Kou, Huai-Rong Luo, Gui-Sheng Wu","doi":"10.1038/s41514-026-00381-x","DOIUrl":"https://doi.org/10.1038/s41514-026-00381-x","url":null,"abstract":"Aging is driven in part by progressive deterioration of proteostasis and antioxidant defense, leading to cellular dysfunction and age-associated disease. The naturally occurring methylated inositol D-pinitol (DP) was reported to present metabolic, antioxidant, and anti-inflammatory effects, as well as to extend the lifespan of D. melanogaster and C. elegans through the insulin/IGF-1 signaling pathway. But the mechanism of DP on delay aging remains poorly understand. Here, we showed that 200 μM of DP increased mean lifespan of C. elegans by 28.6%, as well as healthspan phenotypes including preserved locomotor function and delayed lipofuscin accumulation. DP also attenuated proteotoxicity and delays functional decline in C. elegans models of Parkinson's, Huntington's, and Alzheimer's diseases. Moreover, DP suppressed cellular senescence in multiple mammalian cell types. Genetic and reporter analyses show that DP activates conserved stress-response regulators Nrf2/SKN-1 and HSF-1 through the p38 MAPK signaling cascade to improve resistance to oxidative and thermal stress. DP further enhanced HLH-30-dependent autophagy and mitophagy activities, which are essential for lifespan extension. Together, these findings identify DP as a conserved modulator of proteostasis, redox homeostasis, and autophagy, positioning it as a promising, low-toxicity candidate for promoting healthy aging and mitigating age-related neurodegenerative pathology.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reduction of glycation stress as a geroscience intervention: protocol for a pilot RCT in postmenopausal women. 减少糖基化应激作为一种老年科学干预：绝经后妇女的试点随机对照试验方案。

IF 6

npj aging Pub Date : 2026-04-23 DOI: 10.1038/s41514-026-00373-x

Vineeta Tanwar, Pankaj Kapahi, John C Newman, Brianna Stubbs

{"title":"Reduction of glycation stress as a geroscience intervention: protocol for a pilot RCT in postmenopausal women.","authors":"Vineeta Tanwar, Pankaj Kapahi, John C Newman, Brianna Stubbs","doi":"10.1038/s41514-026-00373-x","DOIUrl":"10.1038/s41514-026-00373-x","url":null,"abstract":"Advanced glycation end products (AGEs) drive metabolic dysfunction, inflammation, and age-related disease, and their accumulation accelerates after menopause. Preclinical studies show that GLYLO, a five-compound glycation-lowering formulation (alpha-lipoic acid, nicotinamide, pyridoxine, benfotiamine, and piperine), reduces AGE burden and improves metabolic health, but its translational relevance in humans is unknown. The Glycation Reduction and Aging: a Clinical Evaluation (GRACE) trial is a randomized, double-blind, placebo-controlled pilot study testing whether six months of GLYLO supplementation lowers circulating AGEs and methylglyoxal (MGO) in postmenopausal women (45-65 years) with elevated adiposity (BMI ≥ 25 kg/m² or waist circumference ≥88 cm) and elevated HbA1c (5.5-6.4%). Secondary and exploratory endpoints include HOMA-IR, body composition, and reproductive hormones, cognitive and physical function, retinal aging, and systemic inflammation. GRACE is designed to address a critical gap in geroscience by evaluating whether targeting glycation can mitigate early metabolic and functional decline in postmenopausal women. ClinicalTrials.gov identifier NCT06813261.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Visual noise in augmented reality improves vision in age-related macular degeneration. 增强现实中的视觉噪声改善了年龄相关性黄斑变性患者的视力。

IF 6

npj aging Pub Date : 2026-04-22 DOI: 10.1038/s41514-026-00389-3

Pratik Raul, Taehwan Lee, Richard Barry, Faran Sabeti, Jeroen J A van Boxtel

{"title":"Visual noise in augmented reality improves vision in age-related macular degeneration.","authors":"Pratik Raul, Taehwan Lee, Richard Barry, Faran Sabeti, Jeroen J A van Boxtel","doi":"10.1038/s41514-026-00389-3","DOIUrl":"https://doi.org/10.1038/s41514-026-00389-3","url":null,"abstract":"Exudative age-related macular degeneration (eAMD) is a degenerative eye disease of the central retina that results in central vision loss, significantly affecting the daily functioning and quality of life of affected individuals. Although first-line treatments are quite effective in improving vision in eAMD, they are invasive and not suitable or efficacious for everyone. The non-invasive methods to enhance visual acuity (VA) in eAMD, are often limited in scope and burdensome for patients. Stochastic resonance (SR), a phenomenon in which optimal noise improves sensory perception, offers a promising non-invasive strategy with broad clinical potential. In this study, we tested whether visual noise delivered via an augmented reality (AR) headset enhanced binocular VA in binocular eAMD (N = 12) and in healthy individuals (N = 17) via the SR effect. Using a standard clinical letter chart, we observed an immediate improvement in vision, without the need for any training. Improvements were 2.5 letters and 2 letters at optimal noise levels for eAMD and healthy individuals, respectively. These findings demonstrate the potential of noise-based AR as a practical, wearable visual aid for individuals with eAMD or other visual disorders, offering enhancements that may complement or extend the benefits of current first-line treatments.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ordinal GWAS analysis of the frailty phenotype identified a novel locus at 12q22 that underscores the role of the neurological and immune systems. 对脆弱表型的有序GWAS分析在12q22发现了一个新的位点，强调了神经系统和免疫系统的作用。

IF 6

npj aging Pub Date : 2026-04-22 DOI: 10.1038/s41514-026-00363-z

Sayem Borhan, Le Minh An Nguyen, Marie Pigeyre, Guillaume Pare, Jonathan Adachi, Alexandra Papaioannou, Lauren E Griffith, Lehana Thabane, Parminder Raina

{"title":"Ordinal GWAS analysis of the frailty phenotype identified a novel locus at 12q22 that underscores the role of the neurological and immune systems.","authors":"Sayem Borhan, Le Minh An Nguyen, Marie Pigeyre, Guillaume Pare, Jonathan Adachi, Alexandra Papaioannou, Lauren E Griffith, Lehana Thabane, Parminder Raina","doi":"10.1038/s41514-026-00363-z","DOIUrl":"https://doi.org/10.1038/s41514-026-00363-z","url":null,"abstract":"Frailty is a complex trait that significantly increases the risk for negative health consequences, including hospitalization and disability. However, the evidence regarding the genetic basis of frailty phenotype (FP) is very limited. We conducted a genome-wide association study (GWAS) on FP using the data from the Canadian Longitudinal Study on Aging (CLSA). We classified the participants as non-frail, pre-frail, and frail, and performed a GWAS utilizing the ordinal logistic regression adjusted for sex, number of chronic conditions, and 10 principal components. Several post-GWAS analyses, including cis-eQTL analyses, were conducted to investigate the potential functional significance. In total, 23,105 participants and more than 8 million imputed SNPs were included in the analysis. The average age was 63 years, and 50.35% of the participants were female. Most participants were non-frail (11,297; 48.89%) or pre-frail (10,261; 44.41%), whereas only 1547 (6.70%) were frail. One novel genomic variant (rs147311617) at the 12p22 locus was found significant at the level of genome-wide significance (p = 4.98×10 -8). This variant was identified near the PLXNC1 gene. The eQTL analysis identified the role of the SOCS2 gene. Our study demonstrated the role of genes, PLXCN1 and SOCS2, that contribute to frailty through neurological and immunological pathways.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"12 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cohort profile Davos Alzheimer's Collaborative DAC Egypt Cohort. 队列简介达沃斯阿尔茨海默病合作DAC埃及队列。

IF 6

npj aging Pub Date : 2026-04-21 DOI: 10.1038/s41514-026-00378-6

Sara A Moustafa, Salma Mowafi, Gharib Fawi, Mai Othman, Shimaa Heikal, Ahmed Sabry Mohamed, Hossam Habib, Omar Ahmed Hassan, Fares Meghaed, Asmaa Shaaban Youssef, Eman Mohamed Ali, Rehab Moustafa, Mahmoud Mohamed, Mahmoud Moustafa, Jana Sweilam, Malak Wahdan, Shahd Ezzeldin, Nourhan Shebl, Katren Khella, Layal Tantawi, Farah Mahmoud, Zeina Gaballah, Farah Zaki, Esraa Qansuwa, Menna El Taras, Shaimaa Sayed, Mohamed El Sayed, Ibrahim Srour, Shaimaa El Sayed Moustafa, Samra Sameer, El Sayed Gad, Mohamed Sweilam, Mie Rizig, Irene Meier, Vaibhav Narayan, Mohamed Salama

{"title":"Cohort profile Davos Alzheimer's Collaborative DAC Egypt Cohort.","authors":"Sara A Moustafa, Salma Mowafi, Gharib Fawi, Mai Othman, Shimaa Heikal, Ahmed Sabry Mohamed, Hossam Habib, Omar Ahmed Hassan, Fares Meghaed, Asmaa Shaaban Youssef, Eman Mohamed Ali, Rehab Moustafa, Mahmoud Mohamed, Mahmoud Moustafa, Jana Sweilam, Malak Wahdan, Shahd Ezzeldin, Nourhan Shebl, Katren Khella, Layal Tantawi, Farah Mahmoud, Zeina Gaballah, Farah Zaki, Esraa Qansuwa, Menna El Taras, Shaimaa Sayed, Mohamed El Sayed, Ibrahim Srour, Shaimaa El Sayed Moustafa, Samra Sameer, El Sayed Gad, Mohamed Sweilam, Mie Rizig, Irene Meier, Vaibhav Narayan, Mohamed Salama","doi":"10.1038/s41514-026-00378-6","DOIUrl":"10.1038/s41514-026-00378-6","url":null,"abstract":"The Davos Alzheimer's Collaborative (DAC) Egypt Cohort (DAC-Egypt) is a newly established longitudinal study of cognitive aging in a community-based convenience sample of older Egyptian adults. The cohort's purpose is to characterize trajectories of cognitive decline and dementia risk factors in an understudied population, filling a critical gap in aging research in the Middle East. Participants (n = 1,530) aged 55 and above were recruited via regionally diverse convenience sampling, with detailed baseline data collected on demographics, health status, lifestyle, and cognitive function. Cognitive assessments included both traditional neuropsychological testing and innovative digital tools (digital voice/speech & olfactory-sensory assessments) to enable comprehensive monitoring. Key preliminary findings indicated a high prevalence of chronic diseases and notable socioeconomic disparities in cognitive performance among older Egyptians. Blood samples were collected from 98% of participants, and dried blood spot (DBS) cards were obtained for 88% of participants to facilitate future biomarker and genetic research. This study seeks to enrich the scientific field of dementia and Alzheimer's disease and related disorders (ADRD) for early detection and intervention strategies for cognitive health in aging populations.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"12 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mild cognitive impairment cases affect the predictive power of Alzheimer's disease diagnostic models using routine clinical variables. 轻度认知障碍病例影响使用常规临床变量的阿尔茨海默病诊断模型的预测能力。

IF 6

npj aging Pub Date : 2026-04-21 DOI: 10.1038/s41514-026-00390-w

Caitlin A Finney, Artur Shvetcov

{"title":"Mild cognitive impairment cases affect the predictive power of Alzheimer's disease diagnostic models using routine clinical variables.","authors":"Caitlin A Finney, Artur Shvetcov","doi":"10.1038/s41514-026-00390-w","DOIUrl":"https://doi.org/10.1038/s41514-026-00390-w","url":null,"abstract":"Diagnostic models using primary care routine clinical variables have been limited in their ability to identify Alzheimer's disease (AD) patients. In this study, we sought to better understand the effect of mild cognitive impairment (MCI) on the predictive performance of AD diagnostic models. We sourced data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. CatBoost was used to assess the utility of routine clinical variables that are accessible to primary care physicians, such as hematological and blood tests and medical history, in multiclass classification between healthy controls, MCI, and AD. Our results indicated that MCI indeed affected the predictive performance of AD diagnostic models. Of the three subgroups of MCI that we found, this finding was driven by a subgroup of MCI patients who likely have prodromal AD. This work highlights the importance of continuing to focus on better classification of the different types of MCI to improve diagnostic models of AD, rather than focusing on binary classifications between AD and control cases. Future research should focus on distinguishing MCI from prodromal AD as the utmost priority for improving translational AD diagnostic models for primary care physicians.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study. semaglutide在SLIM肝研究中对表观遗传衰老和治疗反应的初步研究。

IF 6

npj aging Pub Date : 2026-04-21 DOI: 10.1038/s41514-026-00383-9

Michael J Corley, Alina P S Pang, Douglas W Kitch, Amy Kantor, Fred Sattler, Pablo F Belaunzaran-Zamudio, Todd T Brown, Alan Landay, Jordan E Lake, Kristine M Erlandson

{"title":"Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study.","authors":"Michael J Corley, Alina P S Pang, Douglas W Kitch, Amy Kantor, Fred Sattler, Pablo F Belaunzaran-Zamudio, Todd T Brown, Alan Landay, Jordan E Lake, Kristine M Erlandson","doi":"10.1038/s41514-026-00383-9","DOIUrl":"https://doi.org/10.1038/s41514-026-00383-9","url":null,"abstract":"Semaglutide, a GLP-1 receptor agonist, improves metabolic health and reduces liver fat in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). This post hoc analysis of the 24-week SLIM LIVER single-arm trial (ACTG A5371, No. NCT04216589, registered 02nd Jan 2020) in 41 PWH with MASLD receiving semaglutide (1.0 mg weekly) aimed to evaluate its effect on epigenetic aging and determine whether changes in epigenetic clocks associate with clinical responsiveness. Over 24 weeks, we observed DunedinPACE median change +0.018 (IQR -0.023 to +0.053), PCDNAmTL -0.006 kb (IQR -0.073 to +0.054), and PCGrimAge +0.54 years (IQR -0.33 to +1.26). Participants with decreased DunedinPACE (41.5%) showed greater liver fat reduction (p = 0.024) and trend towards improved gait speed (p = 0.081). Increased PCDNAmTL was associated with better gait speed (p = 0.012). These data suggest early signals of semaglutide responsiveness and relationships to epigenetic age biomarkers. Epigenetic biomarkers may enhance precision in GLP-1RA therapy and enable noninvasive monitoring of biological aging. Trial Registration: ClinicalTrials.gov ID: NCT04216589, registered 02nd Jan 2020.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global stagnation and misaligned priorities in BPH drug development: a 25-year landscape analysis of clinical trial registries. BPH药物开发的全球停滞和错位优先事项：临床试验注册的25年景观分析。

IF 6

npj aging Pub Date : 2026-04-18 DOI: 10.1038/s41514-026-00387-5

Zexuan Lv, Yi Wang, Chao Lv, Yin Lu, Qiang Cheng, Hongyu Zhang, Bingyang Guo, Fan Gao, Hai Huang, Hongzhao Li, Qing Yuan

{"title":"Global stagnation and misaligned priorities in BPH drug development: a 25-year landscape analysis of clinical trial registries.","authors":"Zexuan Lv, Yi Wang, Chao Lv, Yin Lu, Qiang Cheng, Hongyu Zhang, Bingyang Guo, Fan Gao, Hai Huang, Hongzhao Li, Qing Yuan","doi":"10.1038/s41514-026-00387-5","DOIUrl":"https://doi.org/10.1038/s41514-026-00387-5","url":null,"abstract":"Pharmacological innovation for benign prostatic hyperplasia (BPH) has stagnated. As disease burden rises, whether trial activity is addressing disease-modifying therapy remains unclear, while the published literature captures only reported successes. We reviewed BPH drug trial registrations in ClinicalTrials.gov and ChiCTR (2000-2025), standardized design, phase, status, mechanism, and result-reporting variables, and analyzed 224 eligible trials. Of these, 211 were non-ongoing, but only 55.0% had publicly available results. Among 43 studies targeting prostate volume reduction, 25 (58.1%) reported results and 12 (48.0%) showed efficacy; among 137 targeting volume-independent symptom improvement, 82 (59.9%) reported results and 63 (76.8%) showed efficacy. Classical mechanisms, including α1-adrenergic antagonists (24.6%) and 5α-reductase inhibitors (8.5%), dominated Phase III/IV trials (51.9% and 61.1%), whereas emerging mechanisms were concentrated in Phase I/II trials, accounting for 20.0-50.0% of early-phase research. Most trials evaluated single agents (78.6%), while combination and head-to-head studies were uncommon. Industry sponsorship predicted result disclosure (OR 6.67; P < 0.001); mechanism was associated with reporting overall (P = 0.02) and borderline in Phase III (P = 0.05); enrollment ratio was associated in Phase II (OR 13.97; P = 0.04). BPH drug development remains trapped in symptomatic relief, with limited disease modification and substantial hidden failure, requiring greater priority for disease-modifying mechanisms, transparency, and societal and industry investment.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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