巨噬细胞
炎症
吞噬作用
体外
流式细胞术
细胞
生物
癌症研究
化学
免疫学
分子生物学
细胞生物学
生物化学
作者
Brandon M. Hall,Vitaly Balan,Anatoli S. Gleiberman,Evguenia Strom,Peter Krasnov,Lauren P. Virtuoso,Elena Rydkina,Slavoljub Vujcic,Karina Balan,Ilya Gitlin,Katerina I. Leonova,Alexander Polinsky,Olga B. Chernova,Andrei V. Gudkov
出处
期刊:Aging
[Impact Journals, LLC]
日期:2016-07-06
卷期号:8 (7): 1294-1315
被引量:264
标识
DOI:10.18632/aging.100991
摘要
Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and a target for anti-aging therapies. To understand mechanisms controlling the amount of SCs, we analyzed the phenomenon of rapid clearance of human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded into alginate beads preventing them from immunocyte attack. To identify putative SC killers, we analyzed the content of cell populations in lavage and capsules formed around the SC-containing beads. One of the major cell types attracted by secretory factors of SCs was a subpopulation of macrophages characterized by p16(Ink4a) gene expression and β-galactosidase activity at pH6.0 (β-gal(pH6)), thus resembling SCs. Consistently, mice with p16(Ink4a) promoter-driven luciferase, developed bright luminescence of their peritoneal cavity within two weeks following implantation of SCs embedded in alginate beads. p16(Ink4a)/β-gal(pH6)-expressing cells had surface biomarkers of macrophages F4/80 and were sensitive to liposomal clodronate used for the selective killing of cells capable of phagocytosis. At the same time, clodronate failed to kill bona fide SCs generated in vitro by genotoxic stress. Old mice with elevated proportion of p16(Ink4a)/β-gal(pH6)-positive cells in their tissues demonstrated reduction of both following systemic clodronate treatment, indicating that a significant proportion of cells previously considered to be SCs are actually a subclass of macrophages. These observations point at a significant role of p16(Ink4a)/β-gal(pH6)-positive macrophages in aging, which previously was attributed solely to SCs. They require re-interpretation of the mechanisms underlying rejuvenating effects following eradication of p16(Ink4a)/β-gal(pH6)-positive cells and reconsideration of potential cellular target for anti-aging treatment.
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