Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.
Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.
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DOI：
10.1016/s2666-7568(20)30011-8
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Witham MD
中科院分区：
文献类型：
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作者：
Cox LS;Bellantuono I;Lord JM;Sapey E;Mannick JB;Partridge L;Gordon AL;Steves CJ;Witham MD
2019冠状病毒病大流行有力地提醒人们，由于与衰老和免疫能力下降（免疫衰老）相关的合并症，老年人患传染病的不良后果的风险非常高。护理院的居民特别危险，因为与其他体弱的成年人同居，增加了接触和感染的风险，使生理脆弱性更加严重。免疫衰老不仅增加了对疾病的易感性，而且还削弱了疫苗的有效性1-我们预防感染的最有力工具之一-每年接种流感疫苗在风险最高的老年人群中只有30-40%的有效性。在研制新型冠状病毒疫苗的竞赛中，免疫衰老最有可能阻碍老年人参与试验，而对年轻人（< 65岁）有效的疫苗配方可能不会在老年人中产生免疫力。寻找缓解免疫衰老的方法是改善老龄人口健康的首要任务，但要做到这一点，需要对与年龄相关的衰退和免疫衰老的根本原因有深入的了解。生物衰老导致生理储备的丧失，即细胞、组织或器官系统对生理需求增加的反应超出其基础水平的能力。现在已知这种储备的丧失是由一组离散的生物学机制支撑的，这些机制可以被治疗靶向。一种这样的机制是细胞衰老，导致分泌组织降解蛋白酶加上促炎细胞因子和趋化因子的功能障碍细胞的积累，引起局部和全身性损害。免疫细胞的衰老（例如，通过增殖耗竭），结合通过胸腺萎缩导致的幼稚T细胞耗竭，加剧了年龄相关的对新病原体和疫苗的免疫力丧失。因此，旨在恢复免疫功能和改善组织和器官生理的方法可能对减轻感染对老年人的灾难性影响很重要。Geroprotectors是针对衰老的核心生物机制的药物2，3，并且能够
The COVID-19 pandemic serves as a potent reminder that older people are at very high risk of adverse outcomes from infectious disease because of comorbidities associated with ageing and decreased immunological competence (immunosenescence). Care home residents are particularly at risk because physiological vulnerability is compounded by cohabitation with other frail adults, increasing exposure and risk of infection. Immunosenescence not only increases susceptibility to disease but also blunts the effectiveness of vaccines1—one of our most powerful tools for preventing infections—with annual influenza vaccinations only 30–40% effective in the most at-risk older populations. In the race for creating a vaccine against COVID-19, immunosenescence is most likely to present a disincentive to the inclusion of older people in trials, and vaccine formulations effective in younger people (< 65 years) might not engender immunity in older populations. Finding ways to alleviate immunosenescence is a priority to improve the health of ageing populations, but to do so requires a robust understanding of the underlying causes of age-related decline and immunosenescence.Biological ageing results in loss of physiological reserve—the capacity of a cell, tissue, or organ system to function beyond its basal level in response to increases in physiological demands. This loss of reserve is now known to be underpinned by a discrete set of biological mechanisms that can be therapeutically targeted. One such mechanism is cellular senescence, leading to the accumulation of dysfunctional cells that secrete tissue-degrading proteases plus proinflammatory cytokines and chemokines, causing local and systemic harm. Senescence of immune cells (eg, via proliferative exhaustion), combined with depletion of naive T cells through thymic atrophy, exacerbates age-related loss of immunity to novel pathogens and vaccines. Approaches aimed at restoring immune function and improving tissue and organ physiology are thus likely to be important in mitigating the catastrophic effect of infections on older people. Geroprotectors are drugs that target core biological mechanisms underlying ageing2, 3 and are able to