Hallmark Features of Immunosenescence Are Absent in Familial Longevity
Hallmark Features of Immunosenescence Are Absent in Familial Longevity
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DOI：
10.4049/jimmunol.1001629
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发表时间：
2010-10-15
影响因子：
4.4
通讯作者：
Pawelec, Graham
中科院分区：
文献类型：
--
作者：
Derhovanessian, Evelyna;Maier, Andrea B.;Pawelec, Graham
CMV 血清阳性是老年人纵向研究中与死亡率相关的“免疫风险状况”参数之一，可能会加速免疫衰老。因此，任何影响人类寿命的遗传因素都可能与 CMV 和 CMV 加速免疫衰老的易感性有关。为了验证这一点，我们分析了莱顿长寿研究 (LLS) 中的长寿家庭，其中后代的标准化死亡率降低了 30%，这可能是由于遗传富集。对 97 个 LLS 后代和 97 个对照（他们的伴侣，代表正常群体）之间的血清 C 反应蛋白水平和不同 T 细胞亚群的频率进行了比较。我们还测定了一小群 LLS 受试者和对照中 T 细胞对 CMV 免疫显性抗原作出反应的能力。 CMV 感染与一般人群中幼稚 T 细胞频率的年龄相关减少以及 CD45RA 重新表达和晚期分化效应记忆 T 细胞的积累密切相关，但与长寿家庭成员无关。后者的 C 反应蛋白水平也显着降低，表明与 CMV 感染对照相比，促炎状态较低。最后，来自较高比例后代的 T 细胞对 CMV Ag 产生了增殖反应，与对照组相比，这种反应的幅度更大、特异性更广。我们的数据表明，这些长寿基因丰富的稀有个体不太容易受到通常被认为是免疫衰老标志的巨细胞病毒相关年龄驱动的特征性免疫改变的影响，这可能反映了对病毒更好的免疫控制，并有助于降低死亡率。免疫学杂志，2010，185：4618-4624。
Seropositivity for CMV is one of the parameters of the "immune risk profile" associated with mortality in longitudinal studies of the very elderly and may accelerate immunosenescence. Thus, any genetic factors influencing human longevity may be associated with susceptibility to CMV and CMV-accelerated immunosenescence. To test this, we analyzed long-lived families in the Leiden Longevity Study (LLS) in which offspring enjoy a 30% reduced standardized mortality rate, possibly owing to genetic enrichment. Serum C-reactive protein levels and the frequency of different T cell subsets were compared between 97 LLS offspring and 97 controls (their partners, representing the normal population). We also determined the capacity of T cells to respond against immunodominant Ags from CMV in a smaller group of LLS subjects and controls. CMV infection was strongly associated with an age-related reduction in the frequency of naive T cells and an accumulation of CD45RA-re-expressing and late-differentiated effector memory T cells in the general population, but not in members of long-lived families. The latter also had significantly lower C-reactive protein levels, indicating a lower proinflammatory status compared with CMV-infected controls. Finally, T cells from a higher proportion of offspring mounted a proliferative response against CMV Ags, which was also of greater magnitude and broader specificity than controls. Our data suggest that these rare individuals genetically enriched for longevity are less susceptible to the characteristic CMV-associated age-driven immune alterations commonly considered to be hallmarks of immunosenescence, which might reflect better immunological control of the virus and contribute to their decreased mortality rate. The Journal of Immunology, 2010, 185: 4618-4624.