炎性衰老在血液系统疾病中的研究进展

doi:10.16288/j.yczz.21-261

遗传 ›› 2021, Vol. 43 ›› Issue (12): 1132-1141.doi: 10.16288/j.yczz.21-261

炎性衰老在血液系统疾病中的研究进展

刘紫妍(), 高艾()

首都医科大学公共卫生学院, 北京 100069

收稿日期:2021-10-05 修回日期:2021-11-10 出版日期:2021-12-20 发布日期:2021-11-18
通讯作者: 高艾 E-mail:18801197471@163.com;gaoai428@ccmu.edu.cn
作者简介:刘紫妍,本科在读, 2016 级5年制预防医学。E-mail: 18801197471@163.com
基金资助:
国家自然科学基金项目资助(81773397);国家自然科学基金项目资助(82073520)

Progress on inflamm-aging in hematologic diseases

Ziyan Liu(), Ai Gao()

School of Public Health, Capital Medical University, Beijing 100069, China

Received:2021-10-05 Revised:2021-11-10 Online:2021-12-20 Published:2021-11-18
Contact: Gao Ai E-mail:18801197471@163.com;gaoai428@ccmu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(81773397);Supported by the National Natural Science Foundation of China(82073520)

摘要/Abstract

摘要：

随着人类寿命不断增长,全球人口老龄化加剧,老年性疾病发病率也随之上升。炎性衰老(inflamm-aging)指机体随增龄出现的促炎状态升高的现象。研究表明,炎性衰老与心脑血管疾病、神经退行性病变以及骨关节病变具有一定关联,但其发生机制仍不明确,尤其在血液系统疾病方面的研究也较为少见。全身性炎症如何通过衰老引起造血障碍进而参与血液系统疾病的发生尚不明晰。本文主要从炎性衰老的发生机制、炎性衰老与血液系统疾病的关系等方面展开综述,旨在揭示炎性衰老在血液系统疾病中的可能作用机制,为血液系统疾病的防治策略提供借鉴和参考。

关键词: 炎性衰老, 造血功能障碍, 血液系统疾病

Abstract:

With the increasing human life expectancy, the aging of the global population is intensifying, and the incidence of senile diseases is rising accordingly. Inflamm-aging refers to the phenomenon that the body's pro-inflammatory state increases with age. Studies have shown that inflamm-aging is related to cardiovascular and cerebrovascular diseases, neurodegenerative diseases, and osteoarthropathy, but its mechanism is still unclear, especially in blood system diseases. How systemic inflammation causes hematopoietic disorders through aging and then participates in the occurrence of hematological system diseases remains unclarified. This article reviews the pathogenesis of inflamm-aging, and the relationship between inflamm-aging and hematological diseases. It aims to reveal the possible mechanism of inflamm-aging in hematological diseases and provides a reference for the prevention and treatment of hematological diseases.

Key words: Inflamm-aging, hematopoietic dysfunction, hematological system diseases

刘紫妍, 高艾. 炎性衰老在血液系统疾病中的研究进展[J]. 遗传, 2021, 43(12): 1132-1141.

Ziyan Liu, Ai Gao. Progress on inflamm-aging in hematologic diseases[J]. Hereditas(Beijing), 2021, 43(12): 1132-1141.

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学说	发生机制	参考文献
氧化应激学说	ROS增加以及翻译后蛋白修饰→转导蛋白MyD88分子→激活TLRs信号通路→炎症细胞因子产生→慢性炎症→自由基累积→细胞衰老。	[11,13]
氧化应激学说	ROS→激活NALP3炎症小体→启动NF-κB-caspase1炎症复合体→加工pro IL-1和pro IL-18成为活性细胞因子→引发炎症反应→氧化损伤产物累积→细胞衰老。	[3,12,13]
细胞因子学说	炎性细胞因子→产生ROS并激活ATM/p53/p21(WAF1/Cip1)途径→诱导胆道上皮细胞衰老。	[16]
	大量促炎细胞因子→与CXCR2反应→人成纤维细胞衰老	[17]
	rasGAP SH3结合蛋白1(G3BP1)通过cGAS激活NF-κB和STAT3途径→促进SASP→分泌促炎细胞因子→细胞衰老。	[18]
线粒体功能障碍	衰老伴随MQC过程受损→细胞氧化猝灭(ROS积累)以及DAMPs释放→循环DAMPs与TLRs、NLRP3或干扰素基因DNA传感系统的刺激因子(STING)-胞浆环状GMP-AMP合成酶(cGAS)通路相互作用→激活炎症反应。	[3,20]
肠道微生物群变化	年轻或年老小鼠的LFL→增加野生型小鼠腹腔巨噬细胞p16和SAMHD1表达及NF-κB的激活。p16→抑制细胞周期素依赖性激酶CDK4和CDK6活性→细胞衰老。	[24]

疾病类型	发病机理	参考文献
老年性贫血	衰老→促炎状态升高→下调红系祖细胞EPO受体→影响其增殖分化	[45]
老年性贫血	靶向敲除IL-6或HAMP基因→改善老年鼠红细胞生成受损	[46]
MDS	衰老骨髓微环境DAMPs升高→上调小鼠MDSCs中的促炎因子和ROS→抑制红系集落和终末红细胞生成	[50]
MDS	MDS患者MSC (简称MSC-MDS)中CDKN2B显著上调→细胞周期停滞→MSC-MDS衰老及增殖潜能受损	[51]
AML	TNF-α→ERK-ETS1-IL27Ra信号通路→造血干细胞衰老	[52]
AML	miR-146a缺乏小鼠→炎性细胞因子表达增加→HSCs功能失调	[53]

炎性衰老在血液系统疾病中的研究进展

Progress on inflamm-aging in hematologic diseases

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