Aging Cell最新文献_第7页

Natural Killer Cell Dysfunction Is Emerging During Midlife Obesity. 自然杀伤细胞功能障碍在中年肥胖中出现。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-09-01 DOI: 10.1111/acel.70707

Ruojia Biao, Xudong Wang, Jiantao Fu, Yifan Guo, Junming He, Juan Du

{"title":"Natural Killer Cell Dysfunction Is Emerging During Midlife Obesity.","authors":"Ruojia Biao, Xudong Wang, Jiantao Fu, Yifan Guo, Junming He, Juan Du","doi":"10.1111/acel.70707","DOIUrl":"10.1111/acel.70707","url":null,"abstract":"Individuals in the middle-aged demographic are notably more vulnerable to obesity, facing a higher risk of mortality from all causes. However, it remains unclear whether the reduction in life expectancy is related to dysregulated natural killer (NK) cell function triggered by the microenvironment of adiposity in middle age. In the present study, we observed that healthy middle-aged donors and mice displayed compromised NK cell function compared to their younger counterparts, particularly in males. The quantity and maturation of NK cells were significantly diminished in both spleen and white adipose tissues (WATs), coinciding with an increase in WAT volume and a reduced basal metabolic rate in middle-aged mice. We further established that heightened apoptosis coupled with a reduction in cell proliferation might contribute to the diminished NK cell counts in the spleens of middle-aged mice. NK cell function was significantly reduced in the spleen, bone marrow, and adipose tissues of these middle-aged mice. Young mice with diet-induced obesity also exhibited impaired NK cell function. In summary, our findings indicate a reduction in both the quantity and functional efficacy of NK cells, which is associated with the rising prevalence of obesity during middle age.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 9","pages":"e70707"},"PeriodicalIF":7.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The GLP-1-Mitochondria Axis in Metabolic Aging. glp -1-线粒体轴在代谢衰老中的作用。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70676

Renin Chang, Andy P Tsai, Boyang Wang, Chia-Jung Li

{"title":"The GLP-1-Mitochondria Axis in Metabolic Aging.","authors":"Renin Chang, Andy P Tsai, Boyang Wang, Chia-Jung Li","doi":"10.1111/acel.70676","DOIUrl":"https://doi.org/10.1111/acel.70676","url":null,"abstract":"Metabolic aging underlies a cluster of chronic conditions-type 2 diabetes, cardiovascular disease, sarcopenia, and neurodegeneration-that account for a substantial share of global morbidity and mortality. A common feature is progressive mitochondrial dysfunction: impaired bioenergetics, disrupted quality control, and loss of metabolic resilience. Reduced mitochondrial DNA copy number in peripheral blood leukocytes is associated with cardiometabolic disease and mortality, but pre-analytical variability, dependence on blood-cell composition, and uncertain relationship to tissue-level function mean it should be regarded as a candidate risk-associated biomarker rather than a validated measure of mitochondrial integrity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control, engage pathways implicated in mitochondrial biogenesis, dynamics, and mitophagy; whether these effects reflect direct receptor signaling, indirect consequences of weight loss, or secondary mediators such as interleukin-6 remains debated and appears tissue-dependent. In SELECT, semaglutide reduced major adverse cardiovascular events by 20% in obesity without diabetes, and a 2025 multi-omic study in aged male mice found GLP-1 RA treatment attenuated age-associated molecular signatures despite only modest changes in food intake and body weight. No trial, however, has incorporated a prespecified mitochondrial endpoint, human mechanistic evidence remains limited, and access to these therapies remains uneven worldwide. Here we synthesize mechanistic, preclinical, and clinical evidence for a proposed GLP-1-mitochondria axis, classify this evidence by receptor dependence and translational stage, distinguish disease-specific treatment effects from evidence for aging modification, examine four major controversies, and outline a research and policy agenda for responsible, evidence-graded development of GLP-1-based geroscience interventions.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70676"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRF2 Recovers Ischemic Postconditioning Cardioprotection in Aged Myocardiocytes by Regulating CSNK2A2 Localization and FUNDC1 Dephosphorylation. TRF2通过调节CSNK2A2定位和FUNDC1去磷酸化恢复老年心肌细胞缺血后适应心脏保护作用

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70669

Xuan Zhang, Ji Ma, Ruichen Shu, Yuan Li, Ying Zheng, Yiqing Yin

{"title":"TRF2 Recovers Ischemic Postconditioning Cardioprotection in Aged Myocardiocytes by Regulating CSNK2A2 Localization and FUNDC1 Dephosphorylation.","authors":"Xuan Zhang, Ji Ma, Ruichen Shu, Yuan Li, Ying Zheng, Yiqing Yin","doi":"10.1111/acel.70669","DOIUrl":"10.1111/acel.70669","url":null,"abstract":"Ischemic postconditioning (I/Post), which is an effective intervention by activating endogenous cardioprotective pathways, recovers ischemia/reperfusion injury. However, this intervention is not as effective in older patients, and its mechanism needs to be further investigated. In this study, we found that myocardial telomeric repeat binding factor 2 (TRF2) protein expression in male aged mice (18 months of age) was lower than that in male adult mice (4 months of age). After ligation of the anterior descending branch of the heart to establish an in vivo model of ischemia/reperfusion injury, we found that TRF2 expression was further decreased after I/Post. To investigate the role of TRF2 in cardioprotection in I/Post in the senescent heart, we performed echocardiography, blood biochemical testing, and apoptosis-related detection after injecting adeno-associated virus type 9 overexpressing TRF2 into aged mice. We found that TRF2 improved myocardial I/Post protection in vivo. Knockdown of TRF2 in a cardiomyocyte cell line (HL-1) increased inflammatory factor release and aggravated mitochondrial and DNA damage in senescent myocardiocytes following hypoxic postconditioning (H/Post). TRF2 also inhibited activation of the cGAS/STING pathway by increasing mitophagy during H/Post in aged myocardiocytes. Moreover, TRF2 interacted with casein kinase 2 alpha 2 polypeptide (CSNK2A2) to regulate the dephosphorylation of FUN14 domain-containing protein 1 (FUNDC1), which contributed to the protective effect of hypoxic postconditioning.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70669"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline. ANGPTL8-AKT2-mTOR轴驱动脂肪衰老和衰老相关功能衰退。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70671

Yi He, Limeng Pan, WenJun Ping, Chen Meng, Xiaoyu Meng, Yaming Guo, Ranran Kan, Yuxi Xiang, Beibei Mao, Siyi Wang, Danpei Li, Xuefeng Yu

{"title":"An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline.","authors":"Yi He, Limeng Pan, WenJun Ping, Chen Meng, Xiaoyu Meng, Yaming Guo, Ranran Kan, Yuxi Xiang, Beibei Mao, Siyi Wang, Danpei Li, Xuefeng Yu","doi":"10.1111/acel.70671","DOIUrl":"10.1111/acel.70671","url":null,"abstract":"Adipose tissue senescence is increasingly recognized as a key driver of systemic aging and age-related functional decline, yet the endocrine regulators that actively promote this process remain poorly defined. Angiopoietin-like protein 8 (ANGPTL8) is a metabolic factor implicated in lipid metabolism and inflammation and has been associated with multiple aging-related disorders. However, its direct role in adipose tissue senescence and organismal aging remains unclear. Here, we identify ANGPTL8 as a previously unrecognized regulator of adipose tissue aging through integrative analyzes of human cohorts, animal models, transcriptomics, and cellular studies. In a large human cohort, circulating ANGPTL8 levels were strongly associated with biological aging and mortality risk and significantly improved machine learning-based models for age and survival prediction. Consistent with these findings, genetic deletion of Angptl8 in mice extended lifespan, attenuated aging-associated functional decline, and reduced senescence markers in adipose tissue. Transcriptomic analyzes revealed age-dependent upregulation of ANGPTL8 in adipocytes accompanied by activation of pro-senescent transcriptional programs. Mechanistically, ANGPTL8 directly interacted with AKT2 and activated the AKT-mTOR-S6K signaling pathway, thereby promoting cell-autonomous adipocyte senescence. Genetic or pharmacological inhibition of this pathway abolished the pro-senescent effects of ANGPTL8. Collectively, our findings identify ANGPTL8 as an endocrine regulator linking metabolic dysfunction to adipose tissue senescence and systemic aging, highlighting the ANGPTL8-AKT2-mTOR axis as a potential therapeutic target for delaying age-associated functional decline.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70671"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types. 人类脑细胞类型间依赖于sasp的衰老旁分泌扩散的特征。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70673

Taylor Russo, Markus Riessland

{"title":"Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types.","authors":"Taylor Russo, Markus Riessland","doi":"10.1111/acel.70673","DOIUrl":"10.1111/acel.70673","url":null,"abstract":"One of the defining phenotypes of a senescent cell is the senescence-associated secretory phenotype (SASP), which can propagate senescence in neighboring cells both in vitro and in vivo. Importantly, this paracrine spreading of senescence can act in a cell non-autonomous manner, influencing neighboring cell populations and contributing to immune cell recruitment. As cellular senescence has recently been linked to both age-related neurodegenerative phenotypes and local inflammation and is more clearly defined across brain cell types in a cell-type-dependent manner, an urgent question remains regarding how a cell-type-specific paracrine spreading of senescence occurs in the brain. Here, we set out to profile the cell-type-specific features of the SASP and characterize the directionality of paracrine senescence-spreading between major brain cell types. Through this analysis, we identified key SASP ligand-receptor pairs involved in this paracrine dissemination. Targeting selected factors with specific inhibitors, we ameliorated some aspects of the paracrine spreading of senescence in a brain cell-type-dependent manner. Taken together, we identified specific SASP targets for therapeutic intervention in the context of human brain cells and thereby informed the SASP-dependent reaction of immune cells and age-related tissue dysfunction across both normal aging and models of neurodegenerative disease.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70673"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal Stromal Cell Rejuvenation Strategies to Enhance Clinical Translation in Cell Therapy. 间充质间质细胞再生策略在细胞治疗中的临床应用。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70672

Astrid Sodomaco, Irene Bernardi, Aretha Rambaldi, Pierluigi Lombardi, Maura Rossi, Francesca Paris, Lucia Manzoli, Stefano Ratti, Francesco Alviano

{"title":"Mesenchymal Stromal Cell Rejuvenation Strategies to Enhance Clinical Translation in Cell Therapy.","authors":"Astrid Sodomaco, Irene Bernardi, Aretha Rambaldi, Pierluigi Lombardi, Maura Rossi, Francesca Paris, Lucia Manzoli, Stefano Ratti, Francesco Alviano","doi":"10.1111/acel.70672","DOIUrl":"10.1111/acel.70672","url":null,"abstract":"Cell therapies represent a promising frontier in modern medicine. Mesenchymal stromal cells (MSCs) constitute a valuable source due to their minimal ethical concerns, low immunogenicity, negligible tumorigenicity in vivo, and robust paracrine activity mediated by the secretion of anti-inflammatory and angiogenic factors. Despite these advantages, MSCs undergo rapid replicative senescence accompanied by a progressive loss of stemness markers and functional potency. In this context, cellular rejuvenation has been emerging as a pivotal strategy to restore their original biological features. These approaches aim to modulate the hallmarks of aging; as these processes are highly interconnected, multiple and complementary targets have been proposed. This review aims to discuss and analyze the main rejuvenation strategies reported in the literature for MSCs, with particular attention to approaches that can enhance their functionality and translational potential. In this context, the review focuses on five key categories of interventions: epigenetic modifications, metabolic reprogramming, modulation of cellular senescence, telomere biology, and extracellular vesicles. These strategies represent the fundamental axes through which cellular aging can be counteracted and the efficacy of cell-based therapies improved.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70672"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease. 不同的转座因子转录模式在衰老和阿尔茨海默病中的小胶质细胞。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70653

Randy A Grant, Rachel L Doser, Thomas J LaRocca

{"title":"Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease.","authors":"Randy A Grant, Rachel L Doser, Thomas J LaRocca","doi":"10.1111/acel.70653","DOIUrl":"10.1111/acel.70653","url":null,"abstract":"Microglia, the brain's resident immune cells, are transcriptionally diverse and highly dynamic, but during aging and disease they lose their transcriptomic flexibility and adopt a chronically activated state that is associated with neuroinflammation and pathology. An emerging transcriptomic process that is also increasingly implicated in brain aging, neuroinflammation, and disease is the dysregulation of transposable elements (TEs), repetitive genomic sequences with the potential to cause cellular stress/dysfunction. However, there are limited data on microglial TE transcript patterns in these contexts. Here, we analyzed multiple RNA-seq datasets from isolated human and mouse microglia across aging, Alzheimer's disease (AD), and AD-associated pathology. In contrast to previous observations based on whole-brain tissue and other brain cell types, we found that microglial TE transcript levels remained relatively consistent throughout most of the human lifespan before increasing in late life. We also found that TE transcript levels in microglia from AD patients showed minimal changes compared to age-matched controls, and in RNA-seq analyses of transgenic AD mouse models we observed pathology-associated TE transcript decreases. Subsequent analyses identified inverse associations between TE transcript levels and autophagy/lysosome-related gene expression, and in vitro studies suggested that aging- and AD-relevant stimuli, as well as pharmacological autophagy inhibition, modulate TE transcript expression in cultured human microglia. Together, these data provide novel insight into TE transcript dynamics in microglia, highlighting TE transcript patterns that differ from those observed in whole-brain samples and other cell types in aging and AD.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70653"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting RANKL Prevents Bone Loss, Improves Muscle Function and Extends Lifespan in Progeroid Mice. 靶向RANKL预防骨质流失，改善肌肉功能，延长衰老小鼠寿命

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70655

Sandra Freitas-Rodríguez, Alejandra Valle-Cao, Francisco Rodríguez, Manuel Fernández-Sanjurjo, Benjamín Fernández-García, Vanessa Loredo, María Teresa Fernández-García, Carmen Fiuza-Luces, Alejandro Lucia, Carlos López-Otín, Alejandro López-Soto, Alicia R Folgueras

{"title":"Targeting RANKL Prevents Bone Loss, Improves Muscle Function and Extends Lifespan in Progeroid Mice.","authors":"Sandra Freitas-Rodríguez, Alejandra Valle-Cao, Francisco Rodríguez, Manuel Fernández-Sanjurjo, Benjamín Fernández-García, Vanessa Loredo, María Teresa Fernández-García, Carmen Fiuza-Luces, Alejandro Lucia, Carlos López-Otín, Alejandro López-Soto, Alicia R Folgueras","doi":"10.1111/acel.70655","DOIUrl":"10.1111/acel.70655","url":null,"abstract":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by the early development of pathological features associated with aging, ultimately leading to premature death. HGPS primarily affects tissues of mesenchymal origin, as evidenced by the clinical manifestations characteristic of this premature aging disorder, including, but not limited to, osteoporosis, muscle wasting, lipodystrophy, and cardiovascular disease. In this study, we used preclinical mouse models and both genetic and translational approaches to investigate whether an antiresorptive strategy, based on RANKL targeting, ameliorated the bone loss phenotype of progeroid mice. Here we show that osteocyte-derived RANKL deletion in the Zmpste24-/- mouse model of HGPS reverted bone loss in both long bones and vertebrae. These mice also exhibited increased grip strength and improved endurance capacity. Furthermore, Zmpste24-/- mice showed increased survival upon osteocyte-specific RANKL deletion. Notably, the use of a translational approach based on the administration of a neutralizing antibody against RANKL also restored bone mass, reduced muscle fibrosis, and extended the lifespan of Zmpste24-/- mice. Altogether, these findings support that targeting RANKL exerts a beneficial effect on both osseous and extra-osseous phenotypes of HGPS, suggesting the potential of this therapeutic approach to explore in the treatment of this disease.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70655"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AK050834 Deficiency Prevents Vascular Aging via Opposite Regulation of Two Senescence-Sensitive Genes ATF3 and p21. AK050834缺陷通过两个衰老敏感基因ATF3和p21的相反调控来防止血管衰老。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70670

Haoran Wu, Ping Yang, Yang Liu, Qiuting Li, Xinglin Wang, Linyi Tang, Liyun Li, Ting Huang, Xin Zhang, Chunxiang Zhang

{"title":"AK050834 Deficiency Prevents Vascular Aging via Opposite Regulation of Two Senescence-Sensitive Genes ATF3 and p21.","authors":"Haoran Wu, Ping Yang, Yang Liu, Qiuting Li, Xinglin Wang, Linyi Tang, Liyun Li, Ting Huang, Xin Zhang, Chunxiang Zhang","doi":"10.1111/acel.70670","DOIUrl":"https://doi.org/10.1111/acel.70670","url":null,"abstract":"Vascular aging, not only a victim of vascular cell senescence but also a driving hub of systemic aging, is a complex process in which both anti-aging and pro-aging proteins are involved. Thus, the ideal anti-aging medication should have multiple protein targets; in this case, an lncRNA might be a good choice. AK050834 is a conserved lncRNA, but its roles in vascular biology and vascular aging are currently unknown. Here, we identified that AK050834 was highly expressed in vascular walls and in vascular smooth muscle cells (VSMCs). Notably, AK050834 expression was remarkably increased in aged vessels. By using gain-of-function, loss-of-function, and gene knockout approaches, we identified that AK050834 is a strong regulator of VSMC senescence and vascular aging. In terms of the mechanisms, we found that AK050834 suppressed the expression of the anti-aging protein ATF3 via direct interaction with its promoter, which was further confirmed by a rescue experiment. In addition, AK050834 increased the expression of the pro-aging protein p21 by stabilizing its mRNA. Finally, we found that AK050834 deficiency could effectively prevent vascular aging in mice in vivo. The interesting dual and opposite effects of AK050834 on the anti-aging protein ATF3 and the pro-aging protein p21 suggest that AK050834 might be a novel diagnostic marker as well as an ideal therapeutic and preventive target for vascular aging and many related diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70670"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic Reprogramming of Brain Microglia: Implications for Aging and Aging-Associated Neurodegenerative Diseases. 脑小胶质细胞的代谢重编程：衰老和与衰老相关的神经退行性疾病的意义。

IF 7.1 1区医学

Aging Cell Pub Date : 2026-08-01 DOI: 10.1111/acel.70660

Seokjo Kang, Helen S Goodridge

{"title":"Metabolic Reprogramming of Brain Microglia: Implications for Aging and Aging-Associated Neurodegenerative Diseases.","authors":"Seokjo Kang, Helen S Goodridge","doi":"10.1111/acel.70660","DOIUrl":"10.1111/acel.70660","url":null,"abstract":"Microglia, the resident macrophages of the central nervous system (CNS), are key players in maintaining brain and spinal cord homeostasis and protecting the CNS from damage and disease. During aging, the brain undergoes profound changes-including chronic low-grade inflammation, synaptic dysfunction, and increased vulnerability to neurodegenerative diseases-all of which are closely related to alterations in microglial function. One emerging theme is that microglial metabolism is a crucial determinant of their immune and homeostatic activity. In this mini-review, we explore how metabolic programs shape brain microglial behavior and how these processes change during aging and in neurodegenerative diseases. We first highlight the link between specific metabolic pathways and key microglial functions, including phagocytosis, cytokine production, and the oxidative stress response. We then discuss how microglial metabolism is reprogrammed during healthy aging and in Alzheimer's disease and Parkinson's disease, including sex-specific differences. Finally, we examine regulators that influence microglial metabolic states and discuss how these pathways contribute to disease susceptibility and progression. Collectively, recent findings highlight the central role of metabolic reprogramming in shaping microglial responses during aging and in neurodegenerative diseases. We emphasize the need for integrative studies that consider microglial subsets, sex differences, disease context, and upstream molecular regulators to better understand how microglial metabolism contributes to brain health and pathology. A deeper understanding of these pathways may offer new opportunities for therapeutic strategies aimed at restoring microglial homeostasis and mitigating harmful neuroinflammatory processes.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":"25 8","pages":"e70660"},"PeriodicalIF":7.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0