Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands; Cell Biology and Immunology Group, Wageningen University, De Elst 1, 6709 PG Wageningen, The Netherlands; Department of Immunology, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands; Amsterdam UMC, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands.
Trends Immunol. 2019 Feb;40(2):113-127. doi: 10.1016/j.it.2018.12.007. Epub 2019 Jan 6.
Aging is a complex process with an impact on essentially all organs. Declined cellular repair causes increased damage at genomic and proteomic levels upon aging. This can lead to systemic changes in metabolism and pro-inflammatory cytokine production, resulting in low-grade inflammation, or 'inflammaging'. Tissue macrophages, gatekeepers of parenchymal homeostasis and integrity, are prime inflammatory cytokine producers, as well as initiators and regulators of inflammation. In this opinion piece, we summarize intrinsic alterations in macrophage phenotype and function with age. We propose that alternatively activated macrophages (M2-like), which are yet pro-inflammatory, can accumulate in tissues and promote inflammaging. Age-related increases in endoplasmic reticulum stress and mitochondrial dysfunction might be cell-intrinsic forces driving this unusual phenotype.
衰老是一个复杂的过程，几乎会影响所有器官。随着年龄的增长，细胞修复能力下降会导致基因组和蛋白质组水平的损伤增加。这可能导致代谢和促炎细胞因子产生的全身性变化，从而导致低度炎症，即“炎症衰老”。组织巨噬细胞是实质内稳态和完整性的守门员，是主要的促炎细胞因子产生细胞，也是炎症的启动者和调节者。在这篇观点文章中，我们总结了巨噬细胞表型和功能随年龄的内在变化。我们提出，仍然具有促炎作用的交替激活的巨噬细胞（M2 样）可以在组织中积累并促进炎症衰老。内质网应激和线粒体功能障碍的年龄相关性增加可能是驱动这种异常表型的细胞内在力量。
