npj aging最新文献_第7页

Social isolation of aged mice drives dramatic release of inflammatory lipoxygenase-derived oxylipins. 老年小鼠的社会隔离驱动炎症性脂氧化酶衍生的氧脂素的急剧释放。

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npj aging Pub Date : 2026-05-16 DOI: 10.1038/s41514-026-00405-6

Mareike Wichmann-Costaganna, Raphaëlle Petit, Julia Lindner, Madlen Haase, Vivien Bachmann, Robert Klaus Hofstetter, Markus Werner, Christiane Frahm, Oliver Werz, Patrick Schädel

{"title":"Social isolation of aged mice drives dramatic release of inflammatory lipoxygenase-derived oxylipins.","authors":"Mareike Wichmann-Costaganna, Raphaëlle Petit, Julia Lindner, Madlen Haase, Vivien Bachmann, Robert Klaus Hofstetter, Markus Werner, Christiane Frahm, Oliver Werz, Patrick Schädel","doi":"10.1038/s41514-026-00405-6","DOIUrl":"10.1038/s41514-026-00405-6","url":null,"abstract":"Oxylipins, signalling molecules derived from polyunsaturated fatty acids, act as key mediators controlling inflammatory processes. Ageing fuels the disruption of this network, promoting inflammageing. Social isolation, a common feature of ageing, may contribute to the emergence of pro-inflammatory responses, further aggravating conditions like cognitive decline and frailty. Here, we studied how repeated social isolation impacts inflammation-related oxylipin profiles in seven different organs and serum of aged mice. Additionally, we explored physical exercise as a tool to ameliorate age- and isolation-associated inflammation. Our results show that social isolation induces significant increases in interleukin-1β levels and stimulates a dramatic production of lipoxygenase (LOX)-derived oxylipins in an organ-dependent manner, particularly pronounced in liver, lung, and spleen. Physical exercise failed to mitigate the pro-inflammatory effects induced by social isolation. These effects did not occur in the circulatory system as serum oxylipin levels remained relatively unchanged by isolation. The unexpected and striking elevation of oxylipins across the organs highlights the detrimental effect of social isolation and proposes key roles of oxylipins in stress-related inflammageing.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"12 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960423","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

p75 neurotrophin receptor preserves neuromuscular synapse stability and muscle strength during aging. P75神经营养因子受体在衰老过程中保持神经肌肉突触的稳定性和肌肉力量。

IF 13

npj aging Pub Date : 2026-05-16 DOI: 10.1038/s41514-026-00399-1

Viviana Pérez, Sebastián Aedo-Cares, Francisca Bermedo-García, Jessica Mella, Camila Uribe-Martínez, Francisca C Bronfman, Juan Pablo Henríquez

{"title":"p75 neurotrophin receptor preserves neuromuscular synapse stability and muscle strength during aging.","authors":"Viviana Pérez, Sebastián Aedo-Cares, Francisca Bermedo-García, Jessica Mella, Camila Uribe-Martínez, Francisca C Bronfman, Juan Pablo Henríquez","doi":"10.1038/s41514-026-00399-1","DOIUrl":"10.1038/s41514-026-00399-1","url":null,"abstract":"Age-related decline of the neuromuscular junction (NMJ), the peripheral synapse that controls muscle contraction, contributes to muscle weakness and impaired motor function in aging. The NMJ comprises a motor axon terminal, a skeletal muscle fibre, and terminal Schwann cells (tSC). Neurotrophin signalling is essential for mature NMJ organisation, with the p75 receptor acting as a key regulator of its morphology and function. However, the potential contribution of p75 to age-related NMJ decline remains unexplored. In this study, we used germline p75 knockout (p75⁻/⁻) mice to examine how the lifelong absence of p75 impacts NMJ stability and muscle function during aging through quantitative morphometric analyses, postsynaptic receptor dynamics, muscle histology, and functional strength testing. Although NMJ morphology was preserved, aged p75⁻/⁻ mice exhibited pronounced denervation and reduced tSC coverage, hallmarks of age-associated NMJ degeneration. Moreover, postsynaptic domains of aged p75⁻/⁻ mice displayed reduced stability of membrane-bound acetylcholine receptors. Glycolytic muscle fibres also showed signs of atrophy. Notably, aged p75⁻/⁻ mice exhibited a significant reduction in muscle strength compared with age-matched controls. Together, our findings are consistent with cumulative effects of persistent p75 deficiency on NMJ integrity and function during aging, supporting its potential relevance for interventions aimed at preventing age-associated neuromuscular decline.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950595","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

Vaginal aging: from concealed symptoms to defined biomarkers. 阴道老化：从隐蔽的症状到明确的生物标志物。

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npj aging Pub Date : 2026-05-15 DOI: 10.1038/s41514-026-00404-7

Tong Wu, Yibao Huang, Rui Li, Yin Xie, Mingfu Wu

引用次数: 0

Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies. 老化与眼部疾病中的金属离子：生物学、病理生理学和治疗策略。

IF 13

npj aging Pub Date : 2026-05-14 DOI: 10.1038/s41514-026-00396-4

Chun Zhang, Junying Wu, Xinyue Shen, Yidan Liu, Jieying He, Xintong Zheng, Wen Ding, Zhidong Li, Yingting Zhu, Zhuping Xu, Wenru Su, Xiuxing Liu, Yehong Zhuo

{"title":"Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.","authors":"Chun Zhang, Junying Wu, Xinyue Shen, Yidan Liu, Jieying He, Xintong Zheng, Wen Ding, Zhidong Li, Yingting Zhu, Zhuping Xu, Wenru Su, Xiuxing Liu, Yehong Zhuo","doi":"10.1038/s41514-026-00396-4","DOIUrl":"10.1038/s41514-026-00396-4","url":null,"abstract":"Metal ions are indispensable for sustaining normal cellular functions and preserving tissue integrity, as they participate in enzymatic catalysis, signal transduction, and antioxidant defense. However, dysregulation of metal ion homeostasis, particularly during aging, disrupts cellular balance and significantly drives the development and progression of age-related ocular diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and cataracts. Specifically, metal ions modulate key stress responses that are central to aging and ocular pathogenesis. Excessive accumulation of redox-active metals triggers the generation of reactive oxygen species that induce oxidative damage to lipids, proteins, and DNA. Meanwhile, deficiencies in essential metals, such as iron, zinc, copper, and calcium, impair antioxidant enzyme activity and disrupt DNA repair, exacerbating cellular dysfunction and senescence. The therapeutic potential of these metal chelators and antioxidants in restoring their balance, alleviating oxidative stress, and slowing the progression of age-related ocular diseases has been well documented. A deeper understanding of how metal ions influence these processes is crucial for developing more targeted and effective treatments. This article systematically reviews the roles of metal ions in age-related ocular diseases, with a focus on their effects on stress responses and potential therapeutic strategies.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944315","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

Neural signatures of dual-task walking demands in individuals at risk of cognitive impairment. 认知障碍风险个体双任务行走需求的神经特征。

IF 13

npj aging Pub Date : 2026-05-14 DOI: 10.1038/s41514-026-00402-9

Pierfilippo De Sanctis, Denis Barbusse, Theo Vanneau, Wenzhu B Mowrey, Maya A Hoff, Claudia Schneider, Jeannette R Mahoney, Johanna Wagner, John J Foxe, Sophie Molholm

{"title":"Neural signatures of dual-task walking demands in individuals at risk of cognitive impairment.","authors":"Pierfilippo De Sanctis, Denis Barbusse, Theo Vanneau, Wenzhu B Mowrey, Maya A Hoff, Claudia Schneider, Jeannette R Mahoney, Johanna Wagner, John J Foxe, Sophie Molholm","doi":"10.1038/s41514-026-00402-9","DOIUrl":"10.1038/s41514-026-00402-9","url":null,"abstract":"Difficulties in complex daily activities are a hallmark of dementia syndromes. We examined neural signatures of complex daily activity using electroencephalography in forty-five older adults performing a dual-task walking paradigm. Participants were stratified by risk of cognitive impairment (CI). Brain activation linked to gait-related and cognitive events was recorded during single- and dual-task conditions. We hypothesized that a higher risk of CI is associated with poorer performance and distinct fronto-parietal activation during dual-task walking. Cognitive performance declined during walking, with individuals at higher risk of CI performing worse. Increased brain activity during the cognitive task was associated with a lower risk of CI. Both groups showed increased gait-related activation of sensorimotor and fronto-medial cortices during dual-task walking; however, greater sensorimotor activation was observed in individuals at higher risk of CI. Neural signatures of complex daily activity may help identify early signs of cognitive decline and inform prevention strategies.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944270","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

Region-specific transcriptional signatures of brain aging in the absence of neuropathology at the single-cell level. 在单细胞水平上，在没有神经病理的情况下，脑衰老的区域特异性转录特征。

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npj aging Pub Date : 2026-05-13 DOI: 10.1038/s41514-026-00391-9

Monica E Mesecar, Megan F Duffy, Dominic J Acri, Jinhui Ding, Rebekah G Langston, Syed I Shah, Mike A Nalls, Xylena Reed, Sonja W Scholz, D Thad Whitaker, Pavan K Auluck, Stefano Marenco, Alex R DeCasien, J Raphael Gibbs, Mark R Cookson

{"title":"Region-specific transcriptional signatures of brain aging in the absence of neuropathology at the single-cell level.","authors":"Monica E Mesecar, Megan F Duffy, Dominic J Acri, Jinhui Ding, Rebekah G Langston, Syed I Shah, Mike A Nalls, Xylena Reed, Sonja W Scholz, D Thad Whitaker, Pavan K Auluck, Stefano Marenco, Alex R DeCasien, J Raphael Gibbs, Mark R Cookson","doi":"10.1038/s41514-026-00391-9","DOIUrl":"10.1038/s41514-026-00391-9","url":null,"abstract":"As age is a significant risk factor for multiple neurodegenerative diseases, investigating normal brain aging may help identify molecular events contributing to increased disease risk over time. Single-nucleus RNA sequencing (snRNA-seq) enables analysis of gene expression changes within specific cell-types, offering insights into the molecular mechanisms underlying aging. However, most brain aging snRNA-seq datasets use age-matched controls from studies focused on pathology and sample cortical regions. Therefore, there is a need to investigate non-pathological aging within brain regions vulnerable to age-related diseases. We report a snRNA-seq study of 6 young (20-30 years) and 7 aged (60-85 years) individuals encompassing four different brain regions: the entorhinal cortex, middle temporal gyrus, subventricular zone, and putamen. We captured over 150,000 nuclei representing 10 broad cell-types. Region- and cell-type-specific differential expression analyses identified over 8000 age-associated genes. Notably, within a given cell-type, most of these associations were region-specific. Functional enrichment analyses of gene sets for each cell-type-region subgroup reflected multiple hallmarks of aging, including: proteostasis, interactions with cytokines, vesicular trafficking, metabolism, inflammation, metal ion homeostasis, and cellular senescence. Overall, our findings suggest that unique cell-types exhibit distinct transcriptional aging profiles both at the cell-type level and across different brain regions.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936611","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 life events and biological aging in women over 50: evidence from DNA methylation clocks. 50岁以上女性的生殖生命事件和生物衰老：来自DNA甲基化时钟的证据。

IF 13

npj aging Pub Date : 2026-05-13 DOI: 10.1038/s41514-026-00394-6

Ya-Qian Xu, Jinming Fu, Chongyu Ding, Hui Zhang, Yulu Gong, Darong Hao, Xiao Sun, Ping Zeng, Xiangwei Li

{"title":"Reproductive life events and biological aging in women over 50: evidence from DNA methylation clocks.","authors":"Ya-Qian Xu, Jinming Fu, Chongyu Ding, Hui Zhang, Yulu Gong, Darong Hao, Xiao Sun, Ping Zeng, Xiangwei Li","doi":"10.1038/s41514-026-00394-6","DOIUrl":"10.1038/s41514-026-00394-6","url":null,"abstract":"As global aging intensifies, elucidating reproductive health's epigenetic aging associations is crucial. However, the impact of reproductive history on multi-generational DNA methylation (DNAm) clocks remains insufficiently characterized, representing a significant gap in understanding biological vs. chronological aging divergence. This study analyzed 1117 U.S. women aged 50 or older from NHANES 1999-2002 to examine associations between reproductive history and 12 DNA methylation (DNAm) algorithms. Multivariable linear/logistic regression models assessed associations between reproductive indicators and DNAm age acceleration, adjusting for sociodemographic/biological confounders. The β coefficients represent the change in DNAm age acceleration in years. Pregnancy frequency (per additional pregnancy) showed positive associations with PhenoAgeacc (β = 0.14, 95%CI:0.01-0.27) and GrimAge2Mortacc (β = 0.10, 0.03-0.18). Categorical analyses revealed that high pregnancy parity (≥5) significantly increased the odds of GrimAge2Mortacc (OR = 2.34, 95% CI: 1.15-4.71), while high live birth parity (≥5) was associated with increased odds of HannumAgeacc (OR = 2.57, 95% CI: 1.01-6.92). Most primary associations involving second-generation clocks remained robust after false discovery rate correction. While menarche timing showed no significant associations, later menopause and a longer reproductive lifespan were significantly associated with decelerated biological aging after multiple testing correction. These findings suggest that parity and reproductive timing are associated with biological aging trajectories through methylation mechanisms, advancing our understanding of sex-specific aging drivers.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936617","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

Aging dictates tumor-specific genomic alterations across cancer types. 衰老决定了不同癌症类型的肿瘤特异性基因组变化。

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npj aging Pub Date : 2026-05-12 DOI: 10.1038/s41514-026-00392-8

Isabella N Grabski, Jaime L Schneider, Sara Hanahan, Arvind Ravi, Justin F Gainor, Kevin M Haigis, Rafael A Irizarry, Marcia C Haigis

{"title":"Aging dictates tumor-specific genomic alterations across cancer types.","authors":"Isabella N Grabski, Jaime L Schneider, Sara Hanahan, Arvind Ravi, Justin F Gainor, Kevin M Haigis, Rafael A Irizarry, Marcia C Haigis","doi":"10.1038/s41514-026-00392-8","DOIUrl":"10.1038/s41514-026-00392-8","url":null,"abstract":"Cancer risk increases exponentially with age. As the world's population grows older, the absolute number of cancer diagnoses and cancer-related deaths continues to rise globally, despite declines in age-adjusted cancer mortality in many high-income countries. However, there is still little known about how molecular features of tumors differ according to patient age and how these genomic alterations may impact the treatment of patients of advanced age compared to younger patients who are diagnosed with malignancy. In this study, we survey the largest clinically- and genomically-annotated database available and identify age-associated mutations across distinct cancer types, defined as genes whose mutation rates in cross-sectional cancer populations differ by age. By interrogating paired clinical and genomic data from the AACR Project GENIE database across brain, breast, colorectum, lung, pancreas, and skin cancers, we identified somatic mutations in tumors with distinct age-dependent patterns. We also uncovered age-specific associations in the co-mutation patterns among these genes, demonstrating relationships among mutations that strengthen or weaken with age, as well as connections between age-specific mutation patterns and environmental covariates. Finally, in an exploratory analysis, we observed age-associated trends between PTPRT mutations in lung cancer and clinical response to immune checkpoint inhibitors, highlighting the possibility that certain genomic alterations may differentially associate with outcomes across patient age groups.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936573","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

Circulating levels of insulin-like growth factor binding protein 7 are associated with risks of chronic diseases and death. 胰岛素样生长因子结合蛋白7的循环水平与慢性疾病和死亡的风险有关。

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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

sc-ChromAging: A Single-Cell Chromatin Accessibility-based Clock Decodes Cell-Type-Specific Epigenetic Aging Trajectories. sc-ChromAging：基于单细胞染色质可及性的时钟解码细胞类型特异性表观遗传衰老轨迹。

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npj aging Pub Date : 2026-05-09 DOI: 10.1038/s41514-026-00398-2

Xindi Wei, Youcheng Dong, Hongchang Lai, Junyu Shi

引用次数: 0