Immunity & Ageing最新文献

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Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches. 利用免疫调节防治肌肉疏松症:当前的见解和可能的方法。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-08-05 DOI: 10.1186/s12979-024-00458-9
Ning Zhang, Liting Zhai, Ronald Man Yeung Wong, Can Cui, Sheung-Wai Law, Simon Kwoon-Ho Chow, Stuart B Goodman, Wing-Hoi Cheung
{"title":"Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches.","authors":"Ning Zhang, Liting Zhai, Ronald Man Yeung Wong, Can Cui, Sheung-Wai Law, Simon Kwoon-Ho Chow, Stuart B Goodman, Wing-Hoi Cheung","doi":"10.1186/s12979-024-00458-9","DOIUrl":"10.1186/s12979-024-00458-9","url":null,"abstract":"<p><p>Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 immunology of B-1 cells: from development to aging. B-1 细胞的免疫学:从发育到衰老。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-08-02 DOI: 10.1186/s12979-024-00455-y
Matheus Silvério Mattos, Sofie Vandendriessche, Ari Waisman, Pedro Elias Marques
{"title":"The immunology of B-1 cells: from development to aging.","authors":"Matheus Silvério Mattos, Sofie Vandendriessche, Ari Waisman, Pedro Elias Marques","doi":"10.1186/s12979-024-00455-y","DOIUrl":"10.1186/s12979-024-00455-y","url":null,"abstract":"<p><p>B-1 cells have intricate biology, with distinct function, phenotype and developmental origin from conventional B cells. They generate a B cell receptor with conserved germline characteristics and biased V(D)J recombination, allowing this innate-like lymphocyte to spontaneously produce self-reactive natural antibodies (NAbs) and become activated by immune stimuli in a T cell-independent manner. NAbs were suggested as \"rheostats\" for the chronic diseases in advanced age. In fact, age-dependent loss of function of NAbs has been associated with clinically-relevant diseases in the elderly, such as atherosclerosis and neurodegenerative disorders. Here, we analyzed comprehensively the ontogeny, phenotypic characteristics, functional properties and emerging roles of B-1 cells and NAbs in health and disease. Additionally, after navigating through the complexities of B-1 cell biology from development to aging, therapeutic opportunities in the field are discussed.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Heat-killed probiotic Levilactobacillus brevis MKAK9 and its exopolysaccharide promote longevity by modulating aging hallmarks and enhancing immune responses in Caenorhabditis elegans. 热杀死的益生菌Levilactobacillus brevis MKAK9及其外多糖通过调节衰老标志和增强优雅鼠的免疫反应促进长寿。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-08-02 DOI: 10.1186/s12979-024-00457-w
Arun Kumar, Manti Kumar Saha, Vipin Kumar, Anupam Bhattacharya, Sagar Barge, Ashis K Mukherjee, Mohan C Kalita, Mojibur R Khan
{"title":"Heat-killed probiotic Levilactobacillus brevis MKAK9 and its exopolysaccharide promote longevity by modulating aging hallmarks and enhancing immune responses in Caenorhabditis elegans.","authors":"Arun Kumar, Manti Kumar Saha, Vipin Kumar, Anupam Bhattacharya, Sagar Barge, Ashis K Mukherjee, Mohan C Kalita, Mojibur R Khan","doi":"10.1186/s12979-024-00457-w","DOIUrl":"10.1186/s12979-024-00457-w","url":null,"abstract":"<p><strong>Background: </strong>Proteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases.</p><p><strong>Results: </strong>This study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors.</p><p><strong>Conclusion: </strong>Our research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Correction: Single-cell landscape of immunological responses in elderly patients with sepsis. 更正:老年败血症患者免疫反应的单细胞图谱。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-08-02 DOI: 10.1186/s12979-024-00456-x
Wanxue He, Chen Yao, Kaifei Wang, Zhimei Duan, Shuo Wang, Lixin Xie
{"title":"Correction: Single-cell landscape of immunological responses in elderly patients with sepsis.","authors":"Wanxue He, Chen Yao, Kaifei Wang, Zhimei Duan, Shuo Wang, Lixin Xie","doi":"10.1186/s12979-024-00456-x","DOIUrl":"10.1186/s12979-024-00456-x","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling. 通过混合免疫克服年龄依赖性 SARS-CoV-2 疫苗反应:利用质谱分析体液免疫和细胞免疫。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-30 DOI: 10.1186/s12979-024-00454-z
Zayakhuu Gerelkhuu, Sehee Park, Kyoung Hwa Lee, Yong Chan Kim, Sook Jin Kwon, Kyoung-Ho Song, Eu Suk Kim, Young Goo Song, Yoon Soo Park, Jin Young Ahn, Jun Yong Choi, Won Suk Choi, Seongman Bae, Sung-Han Kim, Shin-Woo Kim, Ki Tae Kwon, Hye Won Jeong, Kyong Ran Peck, Eun-Suk Kang, June-Young Koh, Jae-Hoon Ko, Tae Hyun Yoon
{"title":"Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.","authors":"Zayakhuu Gerelkhuu, Sehee Park, Kyoung Hwa Lee, Yong Chan Kim, Sook Jin Kwon, Kyoung-Ho Song, Eu Suk Kim, Young Goo Song, Yoon Soo Park, Jin Young Ahn, Jun Yong Choi, Won Suk Choi, Seongman Bae, Sung-Han Kim, Shin-Woo Kim, Ki Tae Kwon, Hye Won Jeong, Kyong Ran Peck, Eun-Suk Kang, June-Young Koh, Jae-Hoon Ko, Tae Hyun Yoon","doi":"10.1186/s12979-024-00454-z","DOIUrl":"10.1186/s12979-024-00454-z","url":null,"abstract":"<p><strong>Background: </strong>Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear.</p><p><strong>Methods: </strong>This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points.</p><p><strong>Results: </strong>We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4<sup>+</sup> and CD8<sup>+</sup> T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4<sup>+</sup> T, CD8<sup>+</sup> T<sub>EM</sub>, CD8<sup>+</sup> T<sub>EMRA</sub>, and T<sub>FH</sub> cells, increased with age.</p><p><strong>Conclusions: </strong>Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks. 辐射和微重力在航天相关免疫健康风险中的协同作用。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-20 DOI: 10.1186/s12979-024-00449-w
Anna Wadhwa, Maria Moreno-Villanueva, Brian Crucian, Honglu Wu
{"title":"Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks.","authors":"Anna Wadhwa, Maria Moreno-Villanueva, Brian Crucian, Honglu Wu","doi":"10.1186/s12979-024-00449-w","DOIUrl":"10.1186/s12979-024-00449-w","url":null,"abstract":"<p><p>Spaceflight poses a myriad of environmental stressors to astronauts´ physiology including microgravity and radiation. The individual impacts of microgravity and radiation on the immune system have been extensively investigated, though a comprehensive review on their combined effects on immune system outcomes is missing. Therefore, this review aims at understanding the synergistic, additive, and antagonistic interactions between microgravity and radiation and their impact on immune function as observed during spaceflight-analog studies such as rodent hindlimb unloading and cell culture rotating wall vessel models. These mimic some, but not all, of the physiological changes observed in astronauts during spaceflight and provide valuable information that should be considered when planning future missions. We provide guidelines for the design of further spaceflight-analog studies, incorporating influential factors such as age and sex for rodent models and standardizing the longitudinal evaluation of specific immunological alterations for both rodent and cellular models of spaceflight exposure.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Assessing serum anti-nuclear antibodies HEp-2 patterns in synucleinopathies. 评估突触核蛋白病的血清抗核抗体 HEp-2 模式。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-18 DOI: 10.1186/s12979-024-00453-0
Jonas Folke, Marie Skougaard, Trine-Line Korsholm, Anne-Line Strange Laursen, Lisette Salvesen, Anne-Mette Hejl, Sara Bech, Annemette Løkkegaard, Tomasz Brudek, Sisse Bolm Ditlev, Susana Aznar
{"title":"Assessing serum anti-nuclear antibodies HEp-2 patterns in synucleinopathies.","authors":"Jonas Folke, Marie Skougaard, Trine-Line Korsholm, Anne-Line Strange Laursen, Lisette Salvesen, Anne-Mette Hejl, Sara Bech, Annemette Løkkegaard, Tomasz Brudek, Sisse Bolm Ditlev, Susana Aznar","doi":"10.1186/s12979-024-00453-0","DOIUrl":"10.1186/s12979-024-00453-0","url":null,"abstract":"<p><p>This study investigates the presence of antinuclear antibodies (ANA) in three primary synucleinopathies - Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), compared to healthy controls. Autoinflammatory disorders typically involve the immune system mistakenly attacking the body's own cells and start producing ANA. There is an increasing body of evidence that immune-mediated inflammation is a pathological feature linked to synucleinopathies. To investigate whether this could be autoimmune mediated we analyzed for ANA in the plasma of 25 MSA, 25 PD, and 17 DLB patients, along with 25 healthy controls, using the ANA HEp-2 indirect immunofluorescence antibody assay (ANA HEp-2 IFA). Contrary to initial expectations, results showed ANA HEp-2 positivity in 12% of PD, 8% of MSA patients, 18% of DLB patients, and 17% of healthy controls, indicating no increased prevalence of ANA in synucleinopathies compared to age-matched healthy individuals. Various ANA HEp-2 patterns were identified, but no specific pattern was associated with individual synucleinopathies. We conclude hereby that synucleinopathies are not associated with detectable presence of ANA in plasma.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Deciphering the impact of aging on splenic endothelial cell heterogeneity and immunosenescence through single-cell RNA sequencing analysis. 通过单细胞 RNA 测序分析破解衰老对脾脏内皮细胞异质性和免疫衰老的影响
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-18 DOI: 10.1186/s12979-024-00452-1
Yanjing Huang, Zhong Liu, Mengke Li, Dongliang Wang, Jinguo Ye, Qiuling Hu, Qikai Zhang, Yuheng Lin, Rongxin Chen, Xuanwei Liang, Xingyi Li, Xianchai Lin
{"title":"Deciphering the impact of aging on splenic endothelial cell heterogeneity and immunosenescence through single-cell RNA sequencing analysis.","authors":"Yanjing Huang, Zhong Liu, Mengke Li, Dongliang Wang, Jinguo Ye, Qiuling Hu, Qikai Zhang, Yuheng Lin, Rongxin Chen, Xuanwei Liang, Xingyi Li, Xianchai Lin","doi":"10.1186/s12979-024-00452-1","DOIUrl":"10.1186/s12979-024-00452-1","url":null,"abstract":"<p><strong>Background: </strong>Aging is associated with significant structural and functional changes in the spleen, leading to immunosenescence, yet the detailed effects on splenic vascular endothelial cells (ECs) and their immunomodulatory roles are not fully understood. In this study, a single-cell RNA (scRNA) atlas of EC transcriptomes from young and aged mouse spleens was constructed to reveal age-related molecular changes, including increased inflammation and reduced vascular development and also the potential interaction between splenic endothelial cells and immune cells.</p><p><strong>Results: </strong>Ten clusters of splenic endothelial cells were identified. DEGs analysis across different EC clusters revealed the molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the loss in vascular development function of aged ECs. Notably, four EC clusters with immunological functions were identified, suggesting an Endothelial-to-Immune-like Cell Transition (EndICLT) potentially driven by aging. Pseudotime analysis of the Immunology4 cluster further indicated a possible aging-induced transitional state, potentially initiated by Ctss gene activation. Finally, the effects of aging on cell signaling communication between different EC clusters and immune cells were analyzed.</p><p><strong>Conclusions: </strong>This comprehensive atlas elucidates the complex interplay between ECs and immune cells in the aging spleen, offering new insights into endothelial heterogeneity, reprogramming, and the mechanisms of immunosenescence.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration. 核α-突触核蛋白会加速细胞衰老和神经退行性变。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-12 DOI: 10.1186/s12979-024-00429-0
Tingfu Du, Guoxiang Li, Qinglan Zong, Haiyu Luo, Yue Pan, Kaili Ma
{"title":"Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration.","authors":"Tingfu Du, Guoxiang Li, Qinglan Zong, Haiyu Luo, Yue Pan, Kaili Ma","doi":"10.1186/s12979-024-00429-0","DOIUrl":"10.1186/s12979-024-00429-0","url":null,"abstract":"<p><strong>Background: </strong>The progression of Parkinson's disease (PD) is related to ageing. The accumulation of nuclear alpha-synuclein (α-syn) may accelerate the occurrence of neurodegenerative diseases, but its role in PD remains poorly understood.</p><p><strong>Methods: </strong>In the present study, α-syn expression was specifically targeted to the nucleus by constructing an adeno-associated virus (AAV) vector in which a nuclear localization sequence (NLS) was added to the α-syn coding sequence. Virus-mediated gene transfer, behavioural tests, RNA-Seq, immunohistochemistry, western blotting, and quantitative real-time PCR were then performed.</p><p><strong>Results: </strong>In vivo experiments using a mouse model showed that nuclear α-syn increased the severity of the PD-like phenotype, including the loss of dopaminergic neurons concomitant with motor impairment and the formation of α-syn inclusions. These nuclear inclusions contained α-syn species of high molecular weights and induced strong transcriptional dysregulation, especially induced high expression of p21 and senescence-associated secretory phenotype (SASP)-related genes. In addition, the transcriptional alterations induced by nuclear α-syn were associated with gliosis, inflammation, oxidative and DNA damage, and lysosomal dysfunction, and they eventually accelerated neuronal loss and neurodegeneration.</p><p><strong>Conclusions: </strong>Our results suggest that nuclear α-syn plays a crucial role in PD pathogenesis.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Yixin-Fumai granules modulate autophagy through the PI3K/AKT/FOXO pathway and lead to amelioration of aging mice with sick sinus syndrome. 益心复脉颗粒通过PI3K/AKT/FOXO途径调节自噬,从而改善衰老小鼠的病窦综合征。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-07-06 DOI: 10.1186/s12979-024-00439-y
Lianzi Jin, Ping Hou
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