Cytomegalovirus (CMV), oxidative stress, and inflammation: implications for immunosenescence and age-related diseases in the MARK-AGE population.

IF 4.1 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Laura Cianfruglia, Carlo Fortunato, Gretta Veronica Badillo Pazmay, Alexander Bürkle, María Moreno-Villanueva, Tilman Grune, Daniela Weber, Efstathios S Gonos, Bertrand Friguet, Isabelle Petropoulos, Francesco Piacenza, Maurizio Cardelli, Monia Cecati, Miriam Capri, Claudio Franceschi, Martijn E T Dollé, Eugène Jansen, Birgit Weinberger, Ewa Sikora, Florence Debacq-Chainiaux, Wolfgang Stuetz, Mikko Hurme, P Eline Slagboom, Jürgen Bernhardt, Duncan Talbot, Fabiola Olivieri, Marco Malavolta, Robertina Giacconi
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引用次数: 0

Abstract

Cytomegalovirus (CMV) drives immunosenescence, while its reactivation is associated with inflammation and oxidative stress. This study investigates the interplay between CMV, oxidative stress and inflammation in a cohort of 2065 age-stratified individuals randomly recruited from the general population (RASIG), as part of the MARK-AGE study, to better understand the role of CMV in immunosenescence and its potential impact on age-related diseases. CMV IgG titers were associated with oxidative stress, antioxidant, and inflammatory biomarkers. Stepwise-linear regression identified positive associations with age, BMI, apolipoprotein J (ApoJ/Clu), ceruloplasmin, α-2-macroglobulin, proteasome peptidase activity, and malondialdehyde, and negative associations with α-tocopherol, selenium, and vitamin D. Notably, the associations with ApoJ/Clu and proteasome peptidase activity represent novel findings that point to a potential involvement of proteostasis dysregulation and cellular stress responses in CMV-related immune alterations. Quartile-based analyses revealed significantly lower antioxidant levels (α-tocopherol, selenium, ascorbic acid and vitamin D) and higher oxidative stress markers (plasma 8-isoprostanes, malondialdehyde) in the highest quartile (Q4) compared to lower quartiles. Inflammatory markers (homocysteine, ceruloplasmin and α-2-macroglobulin) ApoJ/Clu and proteasome peptidase activity were elevated in Q4. This group also exhibited a higher prevalence of cardiovascular diseases, hypertension, and diabetes. This study highlights a link between CMV IgG titers, oxidative stress, inflammation, and the prevalence of cardiovascular and metabolic diseases. Our findings suggest that CMV may contribute to immunosenescence through mechanisms involving redox imbalance and dysregulation of protein degradation pathways. Further research is needed to explore the role of CMV reactivation in aging, and its impact on age-related metabolic and cardiovascular diseases.

巨细胞病毒(CMV)、氧化应激和炎症:对MARK-AGE人群免疫衰老和年龄相关疾病的影响
巨细胞病毒(CMV)驱动免疫衰老,而它的再激活与炎症和氧化应激有关。作为MARK-AGE研究的一部分,本研究调查了从普通人群(RASIG)随机招募的2065名年龄分层个体的CMV,氧化应激和炎症之间的相互作用,以更好地了解CMV在免疫衰老中的作用及其对年龄相关疾病的潜在影响。CMV IgG滴度与氧化应激、抗氧化和炎症生物标志物相关。逐步线性回归发现,与年龄、BMI、载脂蛋白J (ApoJ/Clu)、铜蓝蛋白、α-2巨球蛋白、蛋白酶体肽酶活性和丙二醛呈正相关,与α-生育酚、硒和维生素d呈负相关。值得注意的是,与ApoJ/Clu和蛋白酶体肽酶活性的关联代表了新的发现,指出cmv相关免疫改变中蛋白质平衡失调和细胞应激反应的潜在参与。基于四分位数的分析显示,与较低四分位数相比,最高四分位数(Q4)的抗氧化水平(α-生育酚、硒、抗坏血酸和维生素D)明显较低,氧化应激标志物(血浆8-异前列腺素、丙二醛)较高。炎症标志物(同型半胱氨酸、铜蓝蛋白和α-2巨球蛋白)ApoJ/Clu和蛋白酶体肽酶活性在Q4升高。这一群体还表现出更高的心血管疾病、高血压和糖尿病患病率。这项研究强调了CMV IgG滴度、氧化应激、炎症和心血管和代谢疾病患病率之间的联系。我们的研究结果表明,巨细胞病毒可能通过氧化还原失衡和蛋白质降解途径失调的机制促进免疫衰老。CMV再激活在衰老中的作用及其对年龄相关代谢和心血管疾病的影响有待进一步研究。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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