Faculty of Applied Sciences & Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, 173229, India.
Biogerontology. 2021 Dec;22(6):571-587. doi: 10.1007/s10522-021-09936-9. Epub 2021 Sep 6.
An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Our understanding of the biological impact of immunosenescence is relatively well-understood, but such knowledge regarding cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be elucidated. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.
免疫功能受损与组织衰老细胞随年龄积累之间的复杂关系正在迅速显现。免疫系统是独一无二的，因为随着年龄的增长，它经历着免疫衰老和细胞衰老相互包容和有害的过程。虽然诱导免疫衰老和细胞衰老的因素可能是共同的，但这两个过程在根本上是不同的，它们整体上影响衰老的免疫系统。我们对免疫衰老的生物学影响的理解相对较好，但对于免疫细胞中细胞衰老的认识，特别是在巨噬细胞等固有免疫细胞中，才刚刚开始阐明。组织驻留巨噬细胞寿命长，虽然在组织特异性和小生境特异性微环境中发挥作用，但巨噬细胞中的衰老可以直接受到衰老宿主细胞的影响，这可能会影响机体的衰老。此外，年龄相关的免疫代谢变化作为改变巨噬细胞表型和功能的驱动因素的证据，如炎症衰老，也正在出现。本综述描述了衰老巨噬细胞中细胞衰老与免疫衰老的新兴影响、与其他衰老非免疫细胞的生物学相关性，以及已知的免疫代谢调节剂。还回顾了我们目前知识中的空白，以及旨在了解巨噬细胞中细胞衰老及其治疗的策略。
