老年人的生长激素、免疫衰老和疫苗接种失败

José E Belizário, Miguel Garay-Malpartida
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引用次数: 2

摘要

在老龄化人群中,甾体和多肽生长激素分泌的纵向减少与衰老细胞在组织和器官中的积累直接相关。细胞低复制衰老状态是由代谢应激和持续的DNA损伤引起的,这些损伤导致p16INK4a细胞周期抑制剂、视网膜母细胞瘤和p53通路的激活。衰老增加了老年人身体虚弱、少肌症、糖尿病、动脉粥样硬化、传染病和癌症的易感性。由于先天和适应性系统的免疫衰老和免疫反应性降低,老年人对疫苗接种的反应较弱。高剂量的疫苗被推荐用于促进无反应老年人记忆T和B细胞的生长和激活,但不足以提供长期保护。在患有年龄相关疾病、慢性病毒感染和免疫缺陷的人群中,用重组人生长激素治疗已被证明可以再生胸腺并增加原始T细胞CD4+和CD8+T细胞及B细胞亚群。本文综述了老年人衰老生物学及其临床免疫学表现的最新进展。我们描述了可能的免疫机制,通过这种机制,个性化重组生长激素治疗可以延长推荐给老年人的疫苗的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GROWTH HORMONE, IMMUNOSENESCENCE AND VACCINATION FAILURE IN THE ELDERLY

In the aging population, the longitudinal decrease in the secretion of steroidal and polypeptides growth hormones is directly associated with accumulation of senescent cells in tissues and organs. The cellular hypo-replicative senescence state is caused by metabolic stress and persistent DNA damage, which lead to the activation of the p16INK4a cell-cycle inhibitor, retinoblastoma and p53 pathways. Aging increases the susceptibility to physical frailty, sarcopenia, diabetes, atherosclerosis, infectious disease and cancer in the older adults. As a consequence of immunosenescence and reduced immunoreactivity of the innate and adaptive systems, seniors have a weak response to vaccination. The high doses of vaccines have been recommended to boost growth and activation of memory T and B cells in non-responsive older individuals, but it is not sufficient for long-term protection. The treatment with recombinant human growth hormone has been shown to regenerate thymus and increase the repertoire of naive T cells CD4+ and CD8+ T cell and B cell subsets in people with age-related diseases, chronic viral infection and immunodeficiencies. This review presents an update on senescence biology and their clinical immunological manifestations in the elderly. We describe possible immune mechanisms by which personalized recombinant growth hormone therapy could act to prolong the effectiveness of the vaccines recommended to older adults.

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