长寿的免疫遗传学及其与人类内源性逆转录病毒K的关联
Lisa M James1,2,3, Apostolos P Georgopoulos1,2,3,4
1Department of Veterans Affairs Health Care System, The HLA Research Group, Brain Sciences Center, Minneapolis, MN, United States.
Frontiers in aging
|February 19, 2025
概括
某些人类白细胞抗原 (HLA) 基因基因可能通过增强对人类内源逆转录病毒K (HERVK) 的免疫反应来促进长寿. 高的HLA-HERVK结合亲和力是长寿的预测因素,并且在非常老的个体中得到丰富.
科学领域:
- 免疫遗传学 免疫遗传学
- 长寿研究的研究.
- 病毒免疫学 病毒免疫学
背景情况:
- 人类免疫系统利用人类白细胞抗原 (HLA) 分子向T细胞呈现异性抗原,这对于病原体消除至关重要.
- HLA多态性影响抗原结合,可能影响免疫反应的有效性和对与年龄有关的疾病的易感性.
- 调查特定的HLA基因,病毒抗原结合和人类寿命之间的联系对于了解免疫系统弹性至关重要.
研究的目的:
- 测试特定HLA等位基因增强对抗病毒抗原的能力,从而促进长寿的假设.
- 确定HLA-病毒结合亲缘关系是否预测参与者的年龄,以及某些HLA基因是否与异常长寿有关.
- 探索与人类寿命相关的HLA-HERVK结合亲缘关系的作用.
主要方法:
- 高分辨率基因型鉴定用于对986名年龄在24-90岁以上的参与者进行HLA和阿波利波蛋白E的鉴定.
- 在分析中预测了244个已识别的HLA基因和13种常见病毒之间的中位数结合亲缘关系,包括人类内源性逆转录病毒K (HERVK).
- 逐步的多重线性回归分析了参与者的年龄与HLA病毒结合亲缘关系之间的关联.
主要成果:
- 在参与者的年龄和HLA-HERVK结合亲和力 (P = 0.005) 之间发现了显著的正相关性.
- 13个HLA基因 (9 HLA-I,4 HLA-II) 在90岁以上的个体中更为频繁,与其他病毒相比,HERVK的预测结合亲缘关系显著更高.
- 在年轻人和老年人之间没有观察到阿波利波蛋白E基因型的显著差异.
结论:
- HLA-HERVK结合亲和力是长寿的强有力的预测因素.
- 赋予HERVK高结合亲和力的特定HLA基因在百岁老人中被丰富,这表明它在促进长寿方面发挥了作用.
- 这些发现强调了宿主免疫遗传学,病毒暴露和寿命之间的相互作用,突出显示了HLA等位基因在加强对HERVK等病毒的免疫反应中的潜在作用.
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