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Evaluating music interventions to treat depression in people living with dementia 评估音乐干预对痴呆症患者抑郁症的治疗效果。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-09 DOI: 10.1038/s43587-025-01055-1
Hannah Walters
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引用次数: 0
Socioeconomic reforms are needed to address disparities for the aging rural-to-urban migrant workforce in China. 中国需要进行社会经济改革,以解决农村向城市流动劳动力老龄化的差距问题。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-09 DOI: 10.1038/s43587-025-01051-5
Huaxiong Jiang
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引用次数: 0
Author Correction: Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. 作者更正:线粒体自噬诱导剂尿素A对年龄相关免疫衰退的影响:一项随机、安慰剂对照试验。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-05 DOI: 10.1038/s43587-025-01060-4
Dominic Denk, Anurag Singh, Herbert G Kasler, Davide D'Amico, Julia Rey, Lucía Alcober-Boquet, Johanna M Gorol, Christoph Steup, Ritesh Tiwari, Ryan Kwok, Rafael J Argüello, Julie Faitg, Kathrin Sprinzl, Stefan Zeuzem, Valentina Nekljudova, Sibylle Loibl, Eric Verdin, Chris Rinsch, Florian R Greten
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引用次数: 0
Brain neuron-derived WDFY1 induces bone loss. 脑神经元源性WDFY1诱导骨质流失。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-05 DOI: 10.1038/s43587-025-01032-8
Chun-Yuan Chen, Zun Wang, Chun-Gu Hong, Yi-Juan Tan, Yan-Xin Duan, Yi Luo, Xin Wang, Hai-Jin Zeng, Jing-Yao Luo, Teng-Fei Wan, Hao Yin, Xi-Xi Liu, Hao Zhu, Yong Zhou, Zheng-Guang Wang, Ze-Hui He, Xin-Yue Hu, Guo-Wen Hu, Hai-Li Lang, Zhen-Xing Wang, Jia Cao, Shan-Shan Rao, Hui Xie

Brain health is closely linked to bone homeostasis. Skeletal aging is characterized by inadequate bone formation and marrow adiposity, but whether the brain contributes to this imbalance remains unknown. This study shows that aged brain neurons, mainly those in the hippocampus and cerebral cortex, produce excess WD repeat and FYVE domain containing 1 (WDFY1) protein and transfer it to the bone via extracellular vesicles (EVs), leading to bone-fat imbalance and osteoporosis. Increasing brain Wdfy1 expression causes premature skeletal aging. Conversely, suppressing Wdfy1 in the whole brain, hippocampus or neurons, genetically deleting neuronal Wdfy1, and selectively inhibiting neuronal EV release all improve bone health. Mechanistically, WDFY1 binds to the retromer complex to promote the endosome-to-Golgi recycling of cathepsin D and peroxiredoxin 2, thus inhibiting osteogenesis and augmenting adipogenesis. This study identifies the role of aged brain neuronal EVs as an important messenger in triggering bone-fat imbalance by transferring WDFY1 to bone.

大脑健康与骨骼稳态密切相关。骨骼老化的特征是骨骼形成不足和骨髓肥胖,但大脑是否有助于这种不平衡仍然未知。本研究表明,老化的大脑神经元,主要是海马和大脑皮层的神经元,产生过量的WD重复和含有1的FYVE结构域(WDFY1)蛋白,并通过细胞外囊泡(EVs)将其转移到骨骼中,导致骨脂失衡和骨质疏松。大脑Wdfy1表达增加导致骨骼过早老化。相反,抑制全脑、海马或神经元中的Wdfy1,基因删除神经元Wdfy1,选择性抑制神经元EV释放,都能改善骨骼健康。机制上,WDFY1与逆转录复合物结合,促进组织蛋白酶D和过氧化物还氧蛋白2的内体到高尔基体的再循环,从而抑制成骨和增加脂肪生成。本研究确定了衰老的脑神经元ev通过将WDFY1转移到骨骼中,作为触发骨脂失衡的重要信使的作用。
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引用次数: 0
Rejuvenating the aging gut by targeting senescence 通过靶向衰老使衰老的肠道恢复活力。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-02 DOI: 10.1038/s43587-025-01045-3
Marina Kolesnichenko
Aging erodes the regenerative capacity of the gut, which weakens barrier function and repair. Eskiocak, Gewolb, Shah, Rouse, Chowdhury and colleagues show that senescent epithelial cells accumulate and drive this decline. Selective elimination of cells that express the senescence-associated surface marker uPAR using senolytic chimeric antigen receptor T cells restores stem cell function and rejuvenates the aged mouse gut.
衰老会侵蚀肠道的再生能力,从而削弱屏障功能和修复能力。Eskiocak, Gewolb, Shah, Rouse, Chowdhury和他们的同事表明,衰老的上皮细胞积累并推动了这种衰退。使用抗衰老嵌合抗原受体T细胞选择性消除表达衰老相关表面标记物uPAR的细胞可恢复干细胞功能并使衰老小鼠肠道恢复活力。
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引用次数: 0
Squishing, squeezing and stretching age hematopoietic stem cells 挤压、挤压和拉伸使造血干细胞衰老。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-02 DOI: 10.1038/s43587-025-01044-4
Chih-Ling Wang, Mary Mohrin
Two recent studies, from Shang et al. and Mejía-Ramírez et al., identify complementary mechanical mechanisms that regulate hematopoietic stem cell aging: external shear stress and internal nuclear envelope tension. These forces represent an evolutionary tradeoff between immediate immune defense and long-term stem cell maintenance.
最近来自Shang等人和Mejía-Ramírez等人的两项研究发现了调节造血干细胞衰老的互补机械机制:外部剪切应力和内部核膜张力。这些力量代表了即时免疫防御和长期干细胞维护之间的进化权衡。
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引用次数: 0
Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging 剪切应力控制造血干细胞的命运,促进炎症诱导的衰老。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-02 DOI: 10.1038/s43587-025-01039-1
Tongyao Shang, Li Zhao, Shibo Ying, Lida Su, Yue Yang, Jiadong Liu, Yingying Wang, Jipeng Xue, Cheng Cheng, Yixin Wu, Shiyao Chen, Hongmei Dong, Xuequn Chen, Hailin Ma, Qi Zhang, Tingbo Liang, Wei Yang, Ye Feng, Marong Fang, Xinjiang Lu
Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to induce HSC proliferation and myelopoiesis. We show that shear stress induces PIEZO1-mediated ion currents and Ca2+ influx in both mouse and human HSCs, with downstream effects on proliferation and myeloid differentiation mediated via JAM3 and CAPN2 pathways. GsMTx4, a PIEZO1 antagonist, attenuated inflammation-induced aging in mice by inhibiting HSC activation. These findings link the mechanical sensor PIEZO1 to HSC proliferation and myeloid differentiation via multi-tiered signaling, highlighting its role in accelerating inflammation-induced aging. Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.
造血干细胞(Hematopoietic stem cells, hsc)以静止状态存在于骨髓中,但在炎症、细胞因子刺激、神经活动或缺氧的反应下,可以被动员到血液中。慢性炎症是衰老的标志,通过促进髓细胞偏向分化和降低自我更新能力来加速HSC衰老,然而机械刺激在调节这些过程中的作用仍然知之甚少。在这里,我们发现PIEZO1感知血流中的剪切应力,从而诱导HSC增殖和骨髓形成。我们发现剪切应力在小鼠和人造血干细胞中诱导piezo1介导的离子电流和Ca2+内流,并通过JAM3和CAPN2途径介导增殖和骨髓分化的下游影响。GsMTx4是一种PIEZO1拮抗剂,通过抑制HSC激活来减轻小鼠炎症诱导的衰老。这些发现将机械传感器PIEZO1通过多层信号传导与HSC增殖和髓细胞分化联系起来,突出了其在加速炎症诱导衰老中的作用。
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引用次数: 0
Linking single-cell multiomics with GWAS to reveal key regulators of disease risk 将单细胞多组学与GWAS联系起来,揭示疾病风险的关键调节因子。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2026-01-02 DOI: 10.1038/s43587-025-01047-1
We developed scMORE (single-cell multiomics regulon enrichment), a computational framework that integrates single-cell multiomics with genome-wide association study summary statistics to identify transcription factor–chromatin–gene regulatory networks (eRegulons) that underlie complex diseases. Applying scMORE to 31 traits (including Parkinson’s disease), we investigated immune- and aging-associated eRegulons, and revealed how genetic variants shape cell-type-specific regulatory programs.
我们开发了scMORE(单细胞多组学调控富集),这是一个将单细胞多组学与全基因组关联研究汇总统计相结合的计算框架,用于鉴定复杂疾病背后的转录因子-染色质-基因调控网络(eRegulons)。将scMORE应用于31个特征(包括帕金森病),我们研究了免疫和衰老相关的eRegulons,并揭示了遗传变异如何塑造细胞类型特异性调控程序。
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引用次数: 0
Cancer-cell-secreted DDAH1 induces TGF-β1/Smad3 signaling pathway to promote fibrosis and aging in lung 癌细胞分泌的DDAH1诱导TGF-β1/Smad3信号通路促进肺纤维化和衰老。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2025-12-24 DOI: 10.1038/s43587-025-01024-8
Liu Liu, Qianyue Wang, Meng Chen, Haifeng Zhou, Xu Li, Ziqi Yuan, Yong Hu, Chaoqun Wang, Xiaohui Zhang, Sheng Hu, Xiaoting Wu, Meixin Li, Juanjuan Li, Aijun Chen, Wei Yan
Lung aging is a multifactorial series of molecular alterations that leads to gradual deterioration of lung function and increased vulnerability to cancer. Tumor communicates with host organs partially through extracellular vesicles; however, the mechanistic drivers and consequences of lung aging in the context of cancer remain unclear. Here we identify cancer cell-secreted dimethylarginine dimethylaminohydrolase-1 (DDAH1) protein induces citrulline accumulation and promotes lung fibrosis and aging. Mechanistically, our single-cell sequencing and genetic knockout mice evidence that citrulline availability elevation inhibits peptidyl arginine deiminase 4-mediated transforming growth factor-β1 (TGF-β1) citrullination, thereby inducing the TGF-β1/Smad3 signaling pathway in lung fibroblasts. Notably, vacuolar protein sorting assists the packaging of DDAH1 into the late endosomes. The administration of DDAH1 inhibitor reduces fibrosis and alleviates lung aging. Conclusively, our findings reveal tumor-derived DDAH1 protein contributes to citrulline accumulation to promote lung aging, shedding light on the treatment and diagnosis of tumors by inhibiting senescent lung fibroblasts. Liu et al. show that tumor-secreted dimethylarginine dimethylaminohydrolase-1 protein induces citrulline accumulation and promotes lung fibrosis and aging, shedding light on the cancer treatment and diagnosis by inhibiting senescent lung fibroblasts.
肺老化是一系列多因素的分子改变,导致肺功能逐渐恶化,对癌症的易感性增加。肿瘤部分通过细胞外囊泡与宿主器官交流;然而,在癌症背景下,肺衰老的机制驱动因素和后果尚不清楚。在这里,我们发现癌细胞分泌的二甲基精氨酸二甲氨基水解酶-1 (DDAH1)蛋白诱导瓜氨酸积累,促进肺纤维化和衰老。机制上,我们的单细胞测序和基因敲除小鼠证明瓜氨酸有效性升高抑制肽基精氨酸脱亚胺酶4介导的转化生长因子-β1 (TGF-β1)瓜氨酸化,从而诱导肺成纤维细胞中TGF-β1/Smad3信号通路。值得注意的是,液泡蛋白分选有助于DDAH1包装到晚期核内体。给予DDAH1抑制剂可减少纤维化,减轻肺老化。总之,我们的研究结果表明,肿瘤来源的DDAH1蛋白有助于瓜氨酸的积累,从而促进肺衰老,从而通过抑制衰老的肺成纤维细胞来治疗和诊断肿瘤。
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引用次数: 0
CDK3 induces neuronal death and brain atrophy in Alzheimer’s disease CDK3诱导阿尔茨海默病的神经元死亡和脑萎缩。
IF 19.4 Q1 CELL BIOLOGY Pub Date : 2025-12-19 DOI: 10.1038/s43587-025-01026-6
Kai Zhuang, Liu Zi, Xiao Su, Chen Hu, Xinrui Li, Shuzhong Wang, Yujun Xia, Bo Wu, Yuemin Su, Shaokun Chen, Haojie Li, Siqi Wang, Mengdan Wang, Jieyin Li, Wenting Xie, Yanbing Chen, Lige Leng, Huifang Li, Li Zhong, Jiechao Zhou, Yan Liu, Qingsong Liu, Karl Herrup, Jie Zhang
Progressive neuronal loss and brain atrophy are principal determinants of cognitive decline in Alzheimer’s disease (AD), yet most mouse models fail to recapitulate these features. Here we identify cyclin-dependent kinase 3 (CDK3) as a key driver of neurodegeneration in AD. CDK3 is elevated in human AD brains and correlates with disease severity. As laboratory mice carry a nonfunctional Cdk3 mutation, we generated two models with restored CDK3 activity and then crossed to AD backgrounds. Both models exhibited substantial neuronal loss, hippocampal atrophy, and cognitive deficits. Single-nucleus RNA sequencing revealed neurons simultaneously activating cell cycle and cell death pathways, indicating cell cycle reentry-induced death. Proteomics implicated synaptic proteins as CDK3 substrates. Finally, we developed BMX330, an inhibitor of CDK3, which mitigated neuronal death and rescued cognitive decline in CDK3-restored AD mice. These findings position CDK3 as a therapeutic target and provide pathologically relevant AD models. Zhuang, Zi et al. identify cyclin-dependent kinase 3 (CDK3) as a driver of neuron loss in Alzheimer’s disease that is associated with brain atrophy and memory decline in mice. Inhibition of CDK3 (BMX330) is shown to limit neuronal loss and improve cognition.
进行性神经元丧失和脑萎缩是阿尔茨海默病(AD)认知能力下降的主要决定因素,但大多数小鼠模型未能重现这些特征。在这里,我们发现周期蛋白依赖性激酶3 (CDK3)是阿尔茨海默病神经退行性变的关键驱动因素。CDK3在人类AD大脑中升高,并与疾病严重程度相关。由于实验室小鼠携带非功能性Cdk3突变,我们产生了两个具有恢复Cdk3活性的模型,然后交叉到AD背景。两种模型都表现出大量的神经元丢失、海马萎缩和认知缺陷。单核RNA测序显示神经元同时激活细胞周期和细胞死亡通路,提示细胞周期再进入诱导死亡。蛋白质组学暗示突触蛋白是CDK3底物。最后,我们开发了一种CDK3抑制剂BMX330,它可以减轻CDK3修复AD小鼠的神经元死亡并挽救认知能力下降。这些发现将CDK3定位为治疗靶点,并提供了病理相关的AD模型。
{"title":"CDK3 induces neuronal death and brain atrophy in Alzheimer’s disease","authors":"Kai Zhuang,&nbsp;Liu Zi,&nbsp;Xiao Su,&nbsp;Chen Hu,&nbsp;Xinrui Li,&nbsp;Shuzhong Wang,&nbsp;Yujun Xia,&nbsp;Bo Wu,&nbsp;Yuemin Su,&nbsp;Shaokun Chen,&nbsp;Haojie Li,&nbsp;Siqi Wang,&nbsp;Mengdan Wang,&nbsp;Jieyin Li,&nbsp;Wenting Xie,&nbsp;Yanbing Chen,&nbsp;Lige Leng,&nbsp;Huifang Li,&nbsp;Li Zhong,&nbsp;Jiechao Zhou,&nbsp;Yan Liu,&nbsp;Qingsong Liu,&nbsp;Karl Herrup,&nbsp;Jie Zhang","doi":"10.1038/s43587-025-01026-6","DOIUrl":"10.1038/s43587-025-01026-6","url":null,"abstract":"Progressive neuronal loss and brain atrophy are principal determinants of cognitive decline in Alzheimer’s disease (AD), yet most mouse models fail to recapitulate these features. Here we identify cyclin-dependent kinase 3 (CDK3) as a key driver of neurodegeneration in AD. CDK3 is elevated in human AD brains and correlates with disease severity. As laboratory mice carry a nonfunctional Cdk3 mutation, we generated two models with restored CDK3 activity and then crossed to AD backgrounds. Both models exhibited substantial neuronal loss, hippocampal atrophy, and cognitive deficits. Single-nucleus RNA sequencing revealed neurons simultaneously activating cell cycle and cell death pathways, indicating cell cycle reentry-induced death. Proteomics implicated synaptic proteins as CDK3 substrates. Finally, we developed BMX330, an inhibitor of CDK3, which mitigated neuronal death and rescued cognitive decline in CDK3-restored AD mice. These findings position CDK3 as a therapeutic target and provide pathologically relevant AD models. Zhuang, Zi et al. identify cyclin-dependent kinase 3 (CDK3) as a driver of neuron loss in Alzheimer’s disease that is associated with brain atrophy and memory decline in mice. Inhibition of CDK3 (BMX330) is shown to limit neuronal loss and improve cognition.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"6 1","pages":"200-220"},"PeriodicalIF":19.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795751","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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Nature aging
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