IF 13

npj aging Pub Date : 2026-08-22 DOI: 10.1038/s41514-026-00491-6

Reza Gheitasi, Mahnaz Rezaei, Parvaneh Nafisi Fard, Daniela Roel, Sabine Baumgart, Diana Dudziak, Norman Rose, Simon M Petzinna, Thomas Kamradt, Carsten Watzl, Mathias W Pletz, Valentin S Schäfer

引用次数: 0

Exploring the link between body physiology and cognition: the role of the brain and aging. 探索身体生理和认知之间的联系：大脑和衰老的作用。

IF 13

npj aging Pub Date : 2026-07-31 DOI: 10.1038/s41514-026-00456-9

Irina Buianova, Narun Pat

引用次数: 0

FOSL2-driven SASP in endometrial stroma promotes the inflammation of endometriosis. 子宫内膜基质中fosl2驱动的SASP促进了子宫内膜异位症的炎症。

IF 13

npj aging Pub Date : 2026-07-24 DOI: 10.1038/s41514-026-00447-w

Weiwei Shi, Xinyi Tang, Fei Yang, Han Yin, Quan Zhou, Fangyue Sun, Shanbo Ding, Udo Jeschke, Lin Peng

{"title":"FOSL2-driven SASP in endometrial stroma promotes the inflammation of endometriosis.","authors":"Weiwei Shi, Xinyi Tang, Fei Yang, Han Yin, Quan Zhou, Fangyue Sun, Shanbo Ding, Udo Jeschke, Lin Peng","doi":"10.1038/s41514-026-00447-w","DOIUrl":"10.1038/s41514-026-00447-w","url":null,"abstract":"Endometriosis (EMs) is characterized by chronic pelvic inflammation, but the etiology of this inflammation remains poorly understood. The senescence-associated secretory phenotype (SASP), whereby senescent cells secrete pro-inflammatory cytokines, is a potential mechanism. This study investigates the pro-inflammatory SASP in EMs and its underlying influences. Through molecular assays and single-cell RNA-seq analysis, we found a subgroup of endometrial stromal cells (ESCs) marked by SASP in both eutopic endometrium and endometriotic lesions of EMs patients. The transcription factor FOSL2 was aberrantly overexpressed in this ESC subgroup; its overexpression induced cellular senescence and the secretion of SASP factors, while FOSL2 knockdown reversed these effects. Conditioned medium from ESCs with high FOSL2 expression promoted M2 macrophage polarization and recruitment. Mechanistically, FOSL2 overexpression in ESCs was regulated by the PGE2/cAMP/PKA signaling pathway, and FOSL2 modulated SASP through the activation of NF-κB signaling. In conclusion, the SASP in ESCs, regulated by FOSL2, contributes to chronic pelvic inflammation and immune system disruption in EMs patients. Targeting FOSL2 to reverse the SASP may offer a promising therapeutic strategy for EMs.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"12 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586356","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

Early-life sugar rationing, brain aging, and long-term neurodegenerative and psychiatric health outcomes: a population-based natural experiment study. 早期生活糖配给、脑老化和长期神经退行性和精神健康结果：一项基于人群的自然实验研究

IF 13

npj aging Pub Date : 2026-07-22 DOI: 10.1038/s41514-026-00452-z

Xingji Lian, Amei Chen, Xiaoyan Zhu, Yuyu Huang, Chongzhe Yang, Yan Huang, Meilong Ran, Longyan Yin, Bing Zhang

{"title":"Early-life sugar rationing, brain aging, and long-term neurodegenerative and psychiatric health outcomes: a population-based natural experiment study.","authors":"Xingji Lian, Amei Chen, Xiaoyan Zhu, Yuyu Huang, Chongzhe Yang, Yan Huang, Meilong Ran, Longyan Yin, Bing Zhang","doi":"10.1038/s41514-026-00452-z","DOIUrl":"https://doi.org/10.1038/s41514-026-00452-z","url":null,"abstract":"Early-life nutrition is linked to adult brain health, yet evidence from quasi-experimental studies remains scarce. Leveraging the UK's historical sugar rationing as a natural experiment, we examined whether early-life sugar restriction reduces the risk of neurodegenerative and psychiatric disorders in later life. Among 60,394 UK Biobank participants (born 1951-1956), three groups were defined: in-utero-only, in utero plus 2 years, and non-rationed controls. Compared with non-rationed individuals, those exposed to sugar restriction during the first 1000 days after conception, showed significantly lower risks of all-cause dementia (by 27%), Alzheimer's disease (46%), depression (11%), and anxiety (20%). Dose-response analyses revealed stronger protective associations against depression and anxiety when postnatal sugar restriction extended beyond 6 months of age. Sex-stratified analyses showed consistent protective effects in women for Alzheimer's disease, depression, and anxiety. Neuroimaging revealed decelerated brain aging, reflected by a 0.39-year reduction in the brain age gap, alongside structural changes in reduced gray-white matter contrast and larger subcortical volumes, including the hippocampus and thalamus. Minimal associations were observed for in‑utero‑only exposure. These quasi-experimental findings suggest that early-life sugar restriction is associated with attenuated neurobiological aging and lower risks of dementia and psychiatric disorders, highlighting sugar intake as a potential modifiable factor of lifelong brain health.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551888","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

Geroprotective insights into the natural metabolite spermidine in aging and age-related diseases. 天然代谢物亚精胺在衰老和年龄相关疾病中的保护作用。

IF 13

npj aging Pub Date : 2026-07-20 DOI: 10.1038/s41514-026-00448-9

Zhirui Jiang, Sen Tong, James L Kirkland, Yu Sun

引用次数: 0

How epigenetic clocks tick: unpacking the black box by deciphering biological pathways and transcriptomic signatures of accelerated aging. 表观遗传时钟如何运行：通过破译加速衰老的生物途径和转录组特征来打开黑盒子。

IF 13

npj aging Pub Date : 2026-07-20 DOI: 10.1038/s41514-026-00446-x

Thalida Em Arpawong, Steve Cole, Harshanna Badhesha, Jung Ki Kim, Christopher R Beam, Eric T Klopack, Kimberly Siegmund, Bharat Thyagarajan, Eileen M Crimmins

{"title":"How epigenetic clocks tick: unpacking the black box by deciphering biological pathways and transcriptomic signatures of accelerated aging.","authors":"Thalida Em Arpawong, Steve Cole, Harshanna Badhesha, Jung Ki Kim, Christopher R Beam, Eric T Klopack, Kimberly Siegmund, Bharat Thyagarajan, Eileen M Crimmins","doi":"10.1038/s41514-026-00446-x","DOIUrl":"10.1038/s41514-026-00446-x","url":null,"abstract":"Epigenetic clocks derived from DNA methylation robustly predict biological aging, health, and mortality, yet differ substantially in their predictive profiles. The biological processes underlying these differences remain poorly understood. Using data from 3227 participants in the U.S. Health and Retirement Study, with contemporaneous DNA methylation and RNA-sequencing, we examined the five most widely used epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE). We conducted differential gene expression analyses to identify clock-specific gene expression levels and enriched biological pathways, to reveal substantial heterogeneity in the molecular processes captured by each clock. We further derived transcriptomic aging gene scores (TAGS) from differentially expressed genes associated with each age acceleration clock, and evaluated their associations with aging-related phenotypes. TAGS complemented DNAm clocks, and in several cases, showed stronger associations with age-related morbidities and mortality. Findings unveiled more unique than common biological processes underlying clocks, illuminating their internal mechanisms, and advancing their interpretability for aging research and clinical applications.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537945","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

Intermittent chloroquine treatment extends lifespan and prevents mammary hyperplasia in female rats while reducing serum ldl and igfbp3 levels. 间歇性氯喹治疗延长雌性大鼠寿命，防止乳腺增生，同时降低血清ldl和igfbp3水平。

IF 13

npj aging Pub Date : 2026-07-20 DOI: 10.1038/s41514-026-00455-w

Marius Viorel Ionica, Cristin Coman, Anthony William Oliver, Diana-Larisa Ancuta, Thorsten R Doeppner, Dirk M Hermann, Ionica Pirici, Aurel Popa-Wagner

{"title":"Intermittent chloroquine treatment extends lifespan and prevents mammary hyperplasia in female rats while reducing serum ldl and igfbp3 levels.","authors":"Marius Viorel Ionica, Cristin Coman, Anthony William Oliver, Diana-Larisa Ancuta, Thorsten R Doeppner, Dirk M Hermann, Ionica Pirici, Aurel Popa-Wagner","doi":"10.1038/s41514-026-00455-w","DOIUrl":"https://doi.org/10.1038/s41514-026-00455-w","url":null,"abstract":"In a previous study, chloroquine (CLQ) administration extended lifespan in middle-aged male NMRI mice without systemic toxicity, challenging the view that blockage of autophagy is uniformly detrimental. Here, we evaluated a modified step-down intermittent CLQ regimen in aged female Sprague-Dawley rats designed to minimize long-term toxicity while maintaining biological activity. CLQ treatment significantly extended median lifespan and increased maximum lifespan by 19%. Treated rats exhibited a significant ~10-12% reduction in food consumption compared with controls, which may have partially contributed to the longevity effects observed in this study. CLQ administration was also associated with changes in endocrine and metabolic parameters, including alterations in the IGF axis, improved lipid profiles, preserved diurnal thermoregulation, stable reproductive hormone levels, and reduced mammary gland proliferative lesions without evidence of hepatic or renal toxicity within the parameters measured. These findings indicate that intermittent CLQ treatment is associated with extended lifespan and coordinated physiological adaptations in aged rats, while the underlying molecular mechanisms remain to be determined.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538038","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

Systemic mapping of senescence characteristics across septic tissues. 脓毒组织衰老特征的系统制图。

IF 13

npj aging Pub Date : 2026-07-17 DOI: 10.1038/s41514-026-00453-y

Chen Zhou, Yunmeng Bai

{"title":"Systemic mapping of senescence characteristics across septic tissues.","authors":"Chen Zhou, Yunmeng Bai","doi":"10.1038/s41514-026-00453-y","DOIUrl":"https://doi.org/10.1038/s41514-026-00453-y","url":null,"abstract":"Sepsis triggers profound organism-wide disturbances, yet the cellular logic underlying its systemic impact remains poorly defined. By integrating single-cell transcriptomes from six septic tissues, we uncovered a conserved cross-tissue program characterized by inflammation-driven senescence, disrupted intercellular communication, and coordinated transcriptional reprogramming. Senescence signatures were broadly elevated across cell types and strongly coupled to altered communication networks, suggesting that septic stress induces both cell-intrinsic and network-level remodeling. We identified several key transcription factors, with activation of Atf4, Cebpb and Cebpd, alongside repression of Foxo1, Gata4, and Yy1, which might rewire inflammatory and stress-adaptive programs toward senescence-like states. Endothelial and neutrophil populations were inferred to act as the principal amplifiers of this response through predicted Cxcl1-Cxcr2 and Cxcl2-Ackr1 circuits, potentially establishing self-reinforcing inflammatory-senescent loops. Finally, the neutrophil-derived signature serves as a robust molecular adjunct to traditional clinical metrics, significantly improving risk stratification and enhancing the prognostic accuracy for sepsis patients. Together, our findings position sepsis as a potent driver of accelerated immunological aging and provide conserved regulatory mechanisms that may represent therapeutic targets for mitigating both acute injury and long-term sequelae.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475032","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

Network-based discovery of regulatory drivers of cognitive decline in alzheimer's disease. 基于网络发现阿尔茨海默病认知能力下降的调节驱动因素。

IF 13

npj aging Pub Date : 2026-07-16 DOI: 10.1038/s41514-026-00443-0

Danish Anwer, Arina A, Agata Marchi, Eduard Kerkhoven, Annikka Polster

{"title":"Network-based discovery of regulatory drivers of cognitive decline in alzheimer's disease.","authors":"Danish Anwer, Arina A, Agata Marchi, Eduard Kerkhoven, Annikka Polster","doi":"10.1038/s41514-026-00443-0","DOIUrl":"10.1038/s41514-026-00443-0","url":null,"abstract":"Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder marked by progressive cognitive decline, yet its transcriptional regulatory architecture remains poorly understood. Here, we model sample-specific gene regulatory networks (GRNs) from dorsolateral prefrontal cortex transcriptomes of 87 individuals with AD and 67 non-cognitively impaired (NCI) controls and use a machine learning classifier to detect consistent disease-specific network features. This sample-specific network approach captures inter-individual variation in transcriptional regulation and revealed 22 key transcription factor-gene regulations that distinguish AD from NCI with 96% weighted accuracy. The key transcription factor-gene interactions were enriched in pathways central to AD pathology, including synaptic signalling, mitochondrial function, proteostasis, and neuroinflammation. Network analysis uncovered significant differences in regulatory connectivity between AD and controls, with ZNF225, ZNF849, and ZNF548 emerging as AD-specific regulatory hubs. Moreover, several key regulatory edges showed significant correlations with longitudinal cognitive decline, supporting their clinical relevance. Our findings highlight pervasive transcriptional dysregulation in AD, emphasizing sample-specific GRN modelling's value in uncovering regulatory mechanisms.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"12 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474968","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

Reproductive behaviors, genetic susceptibility and accelerated aging risk. 生殖行为、遗传易感性和加速衰老风险。

IF 13

npj aging Pub Date : 2026-07-08 DOI: 10.1038/s41514-026-00440-3

Jinghui Zhong, Deyan Kong, Genpei Luo, Yiran Dong, Mingming Yu, Pan Zhang, Yingjie Xu, Xinfeng Liu, Wen Sun

{"title":"Reproductive behaviors, genetic susceptibility and accelerated aging risk.","authors":"Jinghui Zhong, Deyan Kong, Genpei Luo, Yiran Dong, Mingming Yu, Pan Zhang, Yingjie Xu, Xinfeng Liu, Wen Sun","doi":"10.1038/s41514-026-00440-3","DOIUrl":"https://doi.org/10.1038/s41514-026-00440-3","url":null,"abstract":"We examined the associations of reproductive behaviors and genetic susceptibility with aging indicators among female participants in the UK Biobank. Reproductive behaviors included the number of children ever born (NEB), age at first birth (AFB), age at last birth (ALB), and span of years of births (SYB). Aging indicators included frailty, PhenoAge acceleration, KDM-BA acceleration, and brain age difference (BrainAGE-diff). In multivariable analyses, reproductive behaviors showed nonlinear associations with aging indicators. Women with NEB of 2-3 had lower frailty risk, PhenoAge acceleration, KDM-BA acceleration, and BrainAGE-diff. Later AFB and later ALB were also associated with lower levels of several aging indicators, whereas longer SYB was associated with higher frailty risk and PhenoAge acceleration. Mendelian randomization suggested that genetically predicted higher NEB was associated with higher frailty risk and greater PhenoAge acceleration, while genetically predicted later AFB was associated with lower frailty risk and lower PhenoAge and KDM-BA acceleration. Joint analyses showed that high polygenic risk scores combined with NEB > 3, AFB < 25 years, or SYB ≥ 6 years were associated with higher aging burden, although multiplicative interactions were not statistically significant.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414535","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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