Aging Cell最新文献

{"title":"1275-nm Photobiomodulation Alleviates Brain Drainage Impairment as a Promising Therapeutic Strategy for Aging-Related Neurological Decline.","authors":"Hao Lin, Shaojun Liu, Qihang Yang, Junming Li, Jue Wang, Oxana Semyachkina-Glushkovskaya, Dongyu Li, Tingting Yu, Dan Zhu","doi":"10.1111/acel.70261","DOIUrl":"https://doi.org/10.1111/acel.70261","url":null,"abstract":"<p><p>Aging imposes a significant socioeconomic and healthcare burden worldwide, while effective therapy is still lacking. Impaired brain drainage and excessive accumulation of metabolites and toxins such as advanced glycation end products (AGEs) are characteristics of aging that contribute to the development of neurological disorders. Recent discoveries have highlighted the role of meningeal lymphatic vessels (MLVs) in the clearance of toxic metabolites, cells, tumors, and viruses from the brain, positioning them as significant targets for the treatment of various brain diseases. In this study, we demonstrate that noninvasive 1275-nm photobiomodulation (PBM) effectively improves brain drainage and promotes lymphatic clearance of AGEs in a D-galactose-induced aging model (AM) in male mice, while being safe due to its minimal thermal effects. These improvements are associated with nitric oxide release-mediated dilation of MLVs. PBM can also effectively ameliorate redox imbalance, neuroinflammation, and neuronal damage, as well as improve spatial learning ability and short-term recognition memory in AM mice. These findings introduce a promising and easily accessible strategy for nonpharmacological phototherapy of meningeal brain drainage and neurological decline in individuals with aging and aging-related neurodegenerative diseases, offering high potential for rapid implementation into routine clinical practice.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70261"},"PeriodicalIF":7.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate Secretion by Monocytes as a Determinant of Innate Immune Cell Fitness in Healthy Elderly.","authors":"Lisa Smeehuijzen, Frank Vrieling, Jenny Jansen, Hendrik J P van der Zande, Thomas M Houslay, Gabriele Gross, Janna A van Diepen, Lydia A Afman, Rinke Stienstra","doi":"10.1111/acel.70220","DOIUrl":"https://doi.org/10.1111/acel.70220","url":null,"abstract":"<p><p>Immune cell metabolism is increasingly recognized as an important regulator of immune function, but its role in age-related immune dysfunction, chronic inflammation, and cardiometabolic complications in humans remains incompletely understood. This study investigated the impact of aging on monocyte metabolic and functional signatures in a healthy elderly population. We aimed to leverage these immunometabolic signatures to identify healthy elderly individuals with reduced immune cell fitness and, therefore, potentially at a higher risk for age-related complications. We characterized lactate and cytokine secretion, phagocytic capacity, and glycolytic and oxidative metabolic responses in monocytes from 103 elderly individuals and included 52 young adults as a reference group with healthy immune responses. We observed strong similarities in monocyte functional and metabolic signatures between young adults and elderly individuals. However, monocytes from the elderly secreted significantly more cytokines and displayed more ATP-linked respiration and a reduced proton leak compared to young adults. These significant differences were driven by a subgroup within the elderly population characterized by higher monocyte lactate secretion compared to the remainder of the elderly and young adults and were therefore classified as \"immune-unfit\". The immune-unfit elderly exhibited \"hyperactive\" monocytes, evidenced by significantly higher metabolic and functional signatures. Interestingly, compared to immune-fit individuals, immune-unfit elderly individuals had significantly elevated levels of circulating vascular endothelial growth factor and low-density lipoprotein cholesterol. Hence, we propose lactate secretion from monocytes as a parameter to classify \"immune-unfit\" elderly individuals with divergent immunometabolic properties of monocytes that could reflect increased susceptibility to age-related cardiometabolic complications. Trial Registration: NCT05940337.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70220"},"PeriodicalIF":7.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Cognitive Decline by Restoring Senescent Microglial Function via NF-κB-SREBP1 Pathway Inhibition.","authors":"Aihong Liang, Li Zhang, Jing Peng, Yanan Li, Yunduo Zhou, Chao Yang, Jie Wang, Yizhong Yan, Hua Mei, Jun Zhu, Siqi Wang, Na Xiao, Yu Zhou, Lamei Cheng","doi":"10.1111/acel.70259","DOIUrl":"https://doi.org/10.1111/acel.70259","url":null,"abstract":"<p><p>Aging is a major risk factor for neurodegenerative diseases, yet the role of senescent microglia in age-related cognitive dysfunction remains incompletely understood. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been extensively studied for their significant potential in anti-aging. In this study, we demonstrated that hUC-MSCs ameliorate age-related cognitive decline and downregulate senescence-associated markers in the aged hippocampus. Furthermore, co-culture experiments showed that senescent microglia exacerbate neuronal senescence and neuroinflammation, while also suppressing the apoptosis of senescent neurons. These findings suggested that senescent microglia contribute to age-related cognitive decline by exacerbating neuronal damage and impairing senescent neurons' clearance. We also elucidated a novel mechanism by which hUC-MSCs alleviate age-related cognitive decline by targeting senescent microglia. Specifically, we showed that hUC-MSCs reduce senescence-associated markers, decrease lipid droplet accumulation, and restore phagocytic function in senescent microglia through the inhibition of the NF-κB-SREBP1 pathway. This pathway modulation attenuates neuronal damage and promotes the apoptosis of senescent neurons, facilitating the clearance of damaged neurons. These findings highlight the therapeutic potential of hUC-MSCs in age-related neurodegenerative disorders.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70259"},"PeriodicalIF":7.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain DNA Methylation Atlas of App^NL-G-F Alzheimer's Disease Model Mice Across Age and Region Reveals Choline-Induced Resilience.","authors":"Andre Krunic, Thomas A Bellio, Benjamin Z Cohen, Adam Labadorf, Thor D Stein, Honghuang Lin, Tiffany J Mellott, Jan K Blusztajn","doi":"10.1111/acel.70241","DOIUrl":"https://doi.org/10.1111/acel.70241","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common type of dementia. Current treatments for AD are inadequate, and there is a need to design preventive strategies that would improve the resistance or resilience to AD pathology. Because aberrant brain DNA methylation (DNAm) is associated with hallmarks of AD, we tested the hypothesis that a nutritional approach using choline, an essential nutrient and methyl donor, would modulate DNAm to ameliorate AD pathologies. Previous studies showed that perinatal choline supplementation (PCS) reduced AD-like neuropathology and inflammation while improving cognitive performance in AD mouse models. Here we investigated hippocampal and cerebral cortical DNAm patterns by reduced representation bisulfite sequencing from 3 to 12 months in wild-type (WT) and App^NL-G-F AD model mice fed a 1.1 g/kg control or 5.5 g/kg PCS diet from conception to weaning. App^NL-G-F mice showed extensive CpG DNAm changes, which were associated with the age-dependent progression of amyloidosis. PCS induced genotype-specific DNAm patterns and reversed DNAm changes in multiple genes in App^NL-G-F mice. By associating DNAm with matched transcriptomics, we found that DNAm in App^NL-G-F mice correlated with the expression of microglial genes, while DNAm-associated genes modulated by PCS were related to synaptic function. Moreover, we found that methylation levels of several CpGs were associated with levels of beta amyloidosis, relating epigenetic changes to neuropathology. Overall, our data suggest that DNAm in the brain serves as an epigenetic mechanism for abnormal gene expression in App^NL-G-F mice and indicate that PCS may promote resilience to synaptic dysfunction through modulating DNAm.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70241"},"PeriodicalIF":7.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of Autophagy May Be a Mechanism Behind Healthy Aging.","authors":"Arsun Bektas, Shepherd H Schurman, Julián Candia, Olaya Santiago-Fernández, Susmita Kaushik, Ana Maria Cuervo, Luigi Ferrucci","doi":"10.1111/acel.70246","DOIUrl":"https://doi.org/10.1111/acel.70246","url":null,"abstract":"<p><p>Autophagy is intricately linked with protective cellular processes, including mitochondrial function, proteostasis, and cellular senescence. Animal studies have indicated that autophagy becomes dysfunctional with aging and may contribute to T cell immunosenescence. In humans, it remains unclear whether autophagy is impaired in CD4⁺ T cells as people age. To answer this question, we examined basal and inducible autophagic activity in a series of experiments comparing CD4⁺ T cells from younger (23-35 years old) and older (67-93 years old) healthy donors. We used immunofluorescence to detect LC3 (a marker of autophagosomes and autolysosomes) and LAMP2 (a marker of endolysosomes) in conjunction with bafilomycin A₁ (which inhibits the acidification of lysosomes) and CCCP (a mitochondrial uncoupler) to manipulate autophagic flux. We found a significantly higher autophagy flux in CD4⁺ T cells from older compared to younger donors and a higher number of LC3⁺ compartments among older donors. Since the overall amount of autophagosomes degraded was comparable between the two groups, we concluded that autophagosome biogenesis was reduced in the older group. Rather than a decline, our findings in healthy older donors point toward a compensatory enhancement of human CD4⁺ T cell autophagy with age, which may be a mechanism behind healthy aging.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70246"},"PeriodicalIF":7.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in App^NL-G-F Mice.","authors":"Thomas A Bellio, Andre Krunic, Mary S Campion, Rohan Dupaguntla, Adam Labadorf, Thor D Stein, Honghuang Lin, Tiffany J Mellott, Jan K Blusztajn","doi":"10.1111/acel.70148","DOIUrl":"https://doi.org/10.1111/acel.70148","url":null,"abstract":"<p><p>Alzheimer's disease (AD)-the leading cause of dementia-has no cure, inadequate treatment options, and a limited understanding of prevention measures. We have previously shown that perinatal dietary supplementation with the nutrient choline ameliorates cognitive deficits and reduces amyloidosis across the brain in App^NL-G-F AD model mice. Here, we analyzed transcriptomic abnormalities in these mice and tested the hypothesis that they may be attenuated by perinatal choline supplementation (PCS). Wild-type (WT) and App^NL-G-F dams consumed a diet containing 1.1 (control) or 5 g/kg (supplemented) of choline chloride from 2 weeks prior to mating until weaning. At 3, 6, 9, or 12 months of age, the offspring RNA was sequenced in the hippocampus and cerebral cortex. As compared to WT, the App^NL-G-F mice reared on the control diet had age-dependent upregulation of expression of mRNAs and lncRNAs related to inflammation and reduced expression of mRNAs related to neuronal function. As compared to App^NL-G-F mice on the control diet, PCS App^NL-G-F mice increased expression of synaptic genes and downregulated inflammation-related genes starting at 6 months in the cortex; increased expression of GABAergic function and ATP metabolism genes, and decreased expression of inflammatory genes in the hippocampus at 12 months. These changes counteracted the effects of App^NL-G-F genotype seen in mice on the control diet. The expression of many of these choline-protected genes correlated with clinical dementia rating, inflammation, and tauopathy in human postmortem dorsolateral prefrontal cortex AD samples, indicating their relevance to the disease process. The results suggest that adequate choline intake could be a preventive strategy for AD.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70148"},"PeriodicalIF":7.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Mitochondrial Adenine Nucleotide Translocase 1 (ANT1) Correlates With Aging-Associated Airway Remodeling.","authors":"Roshani Jha, Jian Shi, Maggie J Sedgwick, Justin Sui, Timothy E Corcoran, Corrine R Kliment","doi":"10.1111/acel.70264","DOIUrl":"https://doi.org/10.1111/acel.70264","url":null,"abstract":"<p><p>Aging generates a variety of phenotypes in the lungs with increased alveolar airspaces or emphysema, decreased surface area, and increased disease susceptibility. Senescence, oxidative stress, and mitochondrial dysfunction are known contributory factors. However, the underlying mechanisms promoting unhealthy aging remain unclear. Adenine nucleotide Translocase 1 (ANT1), a mitochondrial ADP/ATP transporter, is important for mitochondrial metabolism. Loss of ANT1 has been implicated in the development of pulmonary fibrosis, a disease characterized by accelerated lung aging, through mitochondrial dysfunction and senescence. To determine the role of ANT1 in normal lung aging, we analyzed aged human lung data from the Human Lung Cell Atlas and evaluated the ANT1-related mechanism in an aged genetic mouse and in vitro models. Analysis of SLC25A4 (ANT1) gene expression in the Human Lung Cell Atlas data from healthy adults (ages 20-80) revealed an age-associated reduction in SLC25A4 in alveolar type 2 pneumocytes (AT2), and airway ciliated and basal cells. Using an Ant1-deficient mouse model, aged Ant1-null mice developed increased airway thickening and airway resistance on lung function testing compared to aged wildtype mice. In human airway epithelial cells, ANT1 knockdown resulted in upregulation of senescence and tissue remodeling genes, including COL8A1. Aged Ant1-null mice and aged human airways similarly had increased p21 expression in AT2 and airway club cells, increased SASP markers, and increased COL8A1 expression in the airways. We demonstrate for the first time that ANT1, an important multifunctional mitochondrial protein, plays a significant role in the pathogenesis of lung aging by regulating senescence and airway matrix remodeling.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70264"},"PeriodicalIF":7.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Associated Inflammatory Monocytes Are Increased in Menopausal Females and Reversed by Hormone Replacement Therapy.","authors":"R P H De Maeyer, J Sikora, O V Bracken, B Shih, A F Lloyd, H Peckham, K Hollett, K Abdelhamid, W Cai, M James, P E Pfeffer, M Vukmanovic-Stejic, A N Akbar, E S Chambers","doi":"10.1111/acel.70249","DOIUrl":"https://doi.org/10.1111/acel.70249","url":null,"abstract":"<p><p>Biological sex is a crucial, but poorly understood variable in age-related susceptibility to infection. Monocytes are important immune cells responsible for initiating and resolving inflammatory responses to infection. While changes in monocyte populations result in increased susceptibility to infection, there is limited research on the impact of age and sex on human monocyte phenotype and function. The aim of this work was to dissect the impact of increasing age and biological sex on human monocyte phenotype and function. Here, we show that older females have increased inflammatory intermediate and non-classical monocytes compared to young. These monocyte subsets were the most inflammatory ex vivo, and their frequency correlated with markers of inflammageing. Proteomic analysis of sorted monocyte populations demonstrated that the three human monocyte subsets have largely distinct phenotypes. Key age-associated protein pathways were identified, including complement cascade and phagocytosis. We confirmed the proteomics findings, showing that circulating C3 concentrations were reduced with age in females but not males. This decrease in complement in older females resulted in reduced monocyte phagocytosis. Crucially, we demonstrate that in peri/menopausal females, hormone replacement therapy (HRT) reversed this expansion in intermediate monocytes and decreased circulating CRP as compared to age-matched controls. Importantly, peri/menopausal females on HRT had increased C3 serum concentrations and significant improvement in monocyte phagocytosis. The data presented here indicate the importance of menopause in aging monocyte phenotype and function. These data highlight the potential use of HRT in restoring monocyte function in females during aging and potentially improving anti-pathogen immunity.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70249"},"PeriodicalIF":7.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of Organ-Specific Proteomic Aging in Relation to Lifestyle, Diseases, and Mortality.","authors":"Qi Wang, Jingting Huang, Qida He, Mengtong Sun, Michael P Snyder, Linyan Li","doi":"10.1111/acel.70251","DOIUrl":"https://doi.org/10.1111/acel.70251","url":null,"abstract":"<p><p>Aging occurs in a heterogeneous manner across different organs, leading to varying risks of chronic diseases and mortality. Biological age offers a more comprehensive reflection of the aging process and is a stronger predictor of disease risk and lifespan. Recent advances in plasma proteomics have enabled the development of organ-specific aging clocks, revealing the distinct aging trajectories and their clinical implications. We used protein-based aging estimators for 11 organs, applying them to plasma data using elastic net regularization. A comprehensive analysis of associations was conducted with 86 lifestyle and environmental factors, 657 diseases through phenome-wide association studies (PheWAS), and all-cause mortality. Our findings revealed that organ aging is influenced by lifestyle factors and baseline health conditions, highlighting its dynamic and modifiable nature. Additionally, accelerated organ aging is associated with a higher incidence of disease and an increased risk of all-cause mortality, particularly when it occurs earlier in life. Our large-scale lifestyle atlas and PheWAS offer actionable insights into the modifiable drivers of organ aging, advancing strategies for disease prevention and longevity.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70251"},"PeriodicalIF":7.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSPA12B Protects Against Age-Related Endothelial Cell Senescence by Regulating STING Degradation.","authors":"Tingting Li, Peilin Zhu, Joseph Adams, Fei Tu, Jialing Wang, Chloe Garbe, Suman Dalal, Krishna Singh, Xiaojin Zhang, Li Liu, David L Williams, Chuanfu Li, Xiaohui Wang","doi":"10.1111/acel.70260","DOIUrl":"https://doi.org/10.1111/acel.70260","url":null,"abstract":"<p><p>Cardiovascular diseases remain the leading cause of mortality worldwide, with aging as a major risk factor. Endothelial cell (EC) dysfunction, driven by cellular senescence, is central to age-related cardiomyopathy. Despite its clinical significance, the molecular mechanisms underlying endothelial senescence remain incompletely defined. In this study, we observed that the expression of the endothelial-specific gene heat shock protein family A member 12B (HSPA12B) declines significantly with age. HSPA12B deficiency in mice accelerates age-related EC senescence and cardiac dysfunction, whereas HSPA12B overexpression mitigates EC senescence, highlighting its protective role against vascular aging. Mechanistically, HSPA12B deficiency impairs X-box binding protein 1 (XBP1) transcriptional activity and consequently reduces the expression of its downstream target genes suppressor/enhancer of lin-12-like (SEL1L) and HMG-CoA reductase degradation protein-1 (HRD1). This disruption compromises endoplasmic reticulum-associated degradation (ERAD) of Stimulator of interferon genes (STING), resulting in persistent activation of the cyclic GMP-AMP synthase (cGAS)-STING pathway, a critical driver of EC senescence. In contrast, increased HSPA12B expression enhances XBP1 nuclear translocation and upregulates SEL1L and HRD1, thereby attenuating age-related STING activation. Importantly, pharmacological inhibition of STING reversed the senescent phenotype caused by HSPA12B deficiency. Similarly, enhancing XBP1 activity restored SEL1L and HRD1 expression, reduced STING activation, and alleviated EC senescence. Conversely, SEL1L deficiency or HRD1 inhibition exacerbated STING activation and abolished the protective effects of HSPA12B. Collectively, these findings reveal a previously unrecognized role for HSPA12B in preserving endothelial homeostasis during aging by regulating XBP1-mediated ER-associated degradation of STING and highlight HSPA12B as a potential therapeutic target for age-related cardiovascular dysfunction.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70260"},"PeriodicalIF":7.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}