Abstract:
Immunosenescence describes dysregulation of the immune system with ageing manifested in both the innate and adaptive immunity, including changes in T-cell checkpoint signaling. Through complex and nuanced process, T-cells lose excitatory signaling pathways and upregulate their inhibitory signaling, leading to ineffective immune responses that contribute to the formation of the ageing phenotype. Here we expand on the expression, function, and clinical potential of targeting the T-cell checkpoint signaling in age and highlight interventions offering the most benefits to older adults\' health. Notably, modifications in vaccination such as with mTOR inhibitors show immediate clinical relevance and good tolerability. Other proposed treatments, including therapies with monoclonal antibodies fail to show clinical efficacy or tolerability needed for implementation at present. Although T-cell co-signaling fits a valuable niche for translational scientists to manage immunosenescence, future study would benefit from the inclusion of older adults with multiple long-term conditions and polypharmacy, ensuring better applicability to actual patients seen in clinical settings.
摘要:
免疫衰老描述了免疫系统随着衰老的失调,表现在先天和适应性免疫中。包括T细胞检查点信号的变化。通过复杂而微妙的过程,T细胞失去兴奋性信号通路并上调其抑制性信号,导致导致衰老表型形成的无效免疫反应。在这里,我们扩展表达式,函数,以及针对年龄的T细胞检查点信号的临床潜力,并强调对老年人健康提供最大益处的干预措施。值得注意的是,对mTOR抑制剂等疫苗接种的修饰显示出直接的临床相关性和良好的耐受性.其他建议的治疗方法,包括使用单克隆抗体的疗法未能显示目前实施所需的临床疗效或耐受性。虽然T细胞共信号适合转化科学家管理免疫衰老的有价值的利基,未来的研究将受益于纳入具有多种长期疾病和多重用药的老年人,确保更好地适用于在临床环境中看到的实际患者。