炎性衰老在血液系统疾病中的研究进展

doi:10.16288/j.yczz.21-261

[an error occurred while processing this directive]

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

• Review • Previous Articles Next Articles

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)

Abstract

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

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

Figures/Tables 3

Table 1

Fig. 1

Table 2

References 59

[1]	Sander M, Oxlund B, Jespersen A, Krasnik A, Mortensen EL, Westendorp RG, Rasmussen LJ. The challenges of human population ageing. Age Ageing, 2015,44(2):185-187.
[2]	da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T. A synopsis on aging-theories, mechanisms and future prospects. Ageing Res Rev, 2016,29:90-112.
[3]	Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: role of inflammation triggers and cytokines. Front Immunol, 2018,9:586.
[4]	Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol, 2018,14(10):576-590.
[5]	Song BY. Research on pathogenesis of inflamm-aging. Journal of Xi'an University(Natural Science Edition), 2019,22(5):85-87.
	宋博雅. 炎性衰老的发生机理研究. 西安文理学院学报(自然科学版), 2019,22(5):85-87.
[6]	Fougère B, Boulanger E, Nourhashémi F, Guyonnet S, Cesari M. Chronic inflammation: accelerator of biological aging. J Gerontol A Biol Sci Med Sci, 2017,72(9):1218-1225.
[7]	Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Chronic inflammation in the etiology of disease across the life span. Nat Med, 2019,25(12):1822-1832.
[8]	Reiter RJ, Tan DX, Rosales-Corral S, Galano A, Zhou XJ, Xu B. Mitochondria: central organelles for melatonin's antioxidant and anti-aging actions. Molecules, 2018,23(2):509.
[9]	Bernatoniene J, Kopustinskiene DM. The role of catechins in cellular responses to oxidative stress. Molecules, 2018,23(4):965.
[10]	Papaconstantinou J. The role of signaling pathways of inflammation and oxidative stress in development of senescence and aging phenotypes in cardiovascular disease. Cells, 2019,8(11):1383.
[11]	Ma CY, Liu ZD, Zhang YL. Immunomodulatory effects of Lectin and TLRs signaling pathway. Science and Technology of Food Industry, 2019,40(24):355-360.
	马成瑶, 刘振东, 张彦龙. 凝集素与TLRs信号通路的免疫调节作用. 食品工业科技, 2019,40(24):355-360.
[12]	Song C, He LJ, Zhang J, Ma H, Yuan XN, Hu GY, Tao LJ, Zhang J, Meng J. Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL-1β/IL-1R1/MyD88/NF-κB pathway. J Cell Mol Med, 2016,20(11):2064-2077.
[13]	Caristia S, Vito MD, Sarro A, Leone A, Pecere A, Zibetti A, Filigheddu N, Zeppegno P, Prodam F, Faggiano F, Marzullo P. Is caloric restriction associated with better healthy aging outcomes? A systematic review and meta-analysis of Randomized Controlled Trials. Nutrients, 2020,12(8):2290.
[14]	Hirokawa K, Utsuyama M, Hayashi Y, Kitagawa M, Makinodan T, Fulop T. Slower immune system aging in women versus men in the Japanese population. Immun Ageing, 2013,10(1):19.
[15]	Rea IM, Maxwell LD, McNerlan SE, Alexander HD, Curran MD, Middleton D, Ross OA. Killer Immunoglobulin- like Receptors (KIR) haplogroups A and B track with natural killer cells and cytokine profile in aged subjects: observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST). Immun Ageing, 2013,10(1):35.
[16]	Xie XC, Zhang Y, Wang Z, Wang SS, Jiang XY, Cui HY, Zhou TT, He Z, Feng H, Guo QQ, Song XY, Cao L. ATM at the crossroads of reactive oxygen species and autophagy. Int J Biol Sci, 2021,17(12):3080-3090.
[17]	Yang J, Liu MM, Hong DC, Zeng MS, Zhang X. The paradoxical role of cellular senescence in cancer. Front Cell Dev Biol, 2021,9:722205.
[18]	Omer A, Barrera MC, Moran JL, Lian XJ, Di Marco S, Beausejour C, Gallouzi IE. G3BP1 controls the senescence-associated secretome and its impact on cancer progression. Nat Commun, 2020,11(1):4979.
[19]	Picca A, Guerra F, Calvani R, Coelho-Junior HJ, Bossola M, Landi F, Bernabei R, Bucci C, Marzetti E. Generation and release of mitochondrial-derived vesicles in health, aging and disease. J Clin Med, 2020,9(5):1440.
[20]	Picca A, Lezza AMS, Leeuwenburgh C, Pesce V, Calvani R, Landi F, Bernabei R, Marzetti E. Fueling Inflamm- aging through mitochondrial dysfunction: mechanisms and molecular targets. Int J Mol Sci, 2017,18(5):993.
[21]	Iske J, Seyda M, Heinbokel T, Maenosono R, Minami K, Nian YQ, Quante M, Falk CS, Azuma H, Martin F, Passos JF, Niemann CU, Tchkonia T, Kirkland JL, Elkhal A, Tullius SG. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation. Nat Commun, 2020,11(1):4289.
[22]	Zapata HJ, Quagliarello VJ. The microbiota and microbiome in aging: potential implications in health and age-related diseases. J Am Geriatr Soc, 2015,63(4):776-781.
[23]	Schütte K, Schulz C, Vilchez-Vargas R, Vasapolli R, Palm F, Simon B, Schomburg D, Lux A, Geffers R, Pieper DH, Link A, Malfertheiner P. Impact of healthy aging on active bacterial assemblages throughout the gastrointestinal tract. Gut Microbes, 2021,13(1):1966261.
[24]	Kim KA, Jeong JJ, Yoo SY, Kim DH. Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice. BMC Microbiol, 2016,16:9.
[25]	Sanders DJ, Inniss S, Sebepos-Rogers G, Rahman FZ, Smith AM. The role of the microbiome in gastrointestinal inflammation. Biosci Rep, 2021, 41(6): BSR20203850.
[26]	DeJong EN, Surette MG, Bowdish DME. The gut microbiota and unhealthy aging: disentangling cause from consequence. Cell Host Microbe, 2020,28(2):180-189.
[27]	Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larché MJ, Davidson DJ, Verdú EF, Surette MG, Bowdish DME. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, macrophage dysfunction. Cell Host Microbe, 2017, 21(4): 455-466.e4.
[28]	Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M, Giampieri E, Jennings A, Candela M, Turroni S, Zoetendal EG, Hermes GDA, Elodie C, Meunier N, Brugere CM, Pujos-Guillot E, Berendsen AM, De Groot L, Feskins EJM, Kaluza J, Pietruszka B, Bielak MJ, Comte B, Maijo-Ferre M, Nicoletti C, De Vos WM, Fairweather-Tait S, Cassidy A, Brigidi P, Franceschi C, O'Toole PW. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut, 2020,69(7):1218-1228.
[29]	Guglielmetti S, Bernardi S, Del Bo’ C, Cherubini A, Porrini M, Gargari G, Hidalgo-Liberona N, Gonzalez- Dominguez R, Peron G, Zamora-Ros R, Winterbone MS, Kirkup B, Kroon PA, Andres-Lacueva C, Riso P. Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial. BMC Geriatr, 2020,20(1):77.
[30]	Mrityunjaya M, Pavithra V, Neelam R, Janhavi P, Halami PM, Ravindra PV. Immune-boosting, antioxidant and anti-inflammatory food supplements targeting pathogenesis of COVID-19. Front Immunol, 2020,11:570122.
[31]	Garrido A, Cruces J, Ceprián N, Vara E, de la Fuente M. Oxidative-inflammatory stress in immune cells from adult mice with premature aging. Int J Mol Sci, 2019,20(3):769.
[32]	Saleh J, Peyssonnaux C, Singh KK, Edeas M. Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. Mitochondrion, 2020,54:1-7.
[33]	Jauhari A, Baranov SV, Suofu Y, Kim J, Singh T, Yablonska S, Li F, Wang XM, Oberly P, Minnigh MB, Poloyac SM, Carlisle DL, Friedlander RM. Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration. J Clin Invest, 2020,130(6):3124-3136.
[34]	Han B, Lin C-CJ, Hu G, Wang MC. ʻInside Outʼ- a dialogue between mitochondria and bacteria. FEBS J, 2019,286(4):630-641.
[35]	Yang DZ, de Haan G. Inflammation and aging of hematopoietic stem cells in their niche. Cells, 2021,10(8):1849.
[36]	Walter D, Lier A, Geiselhart A, Thalheimer FB, Huntscha S, Sbotta MC, Moehrle B, Brocks D, Bayindir I, Kaschutnig P, Muedder K, Klein C, Jauch A, Schroeder T, Geiger H, Dick TP, Holland-Letz T, Schmezer P, Lane SW, Rieger MA, Essers MA, Williams DA, Trumpp A, Milsom MD. Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature, 2015,520(7548):549-552.
[37]	Trowbridge JJ, Starczynowski DT. Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS. J Exp Med, 2021,218(7):e20201544.
[38]	Kovtonyuk LV, Fritsch K, Feng XM, Manz MG, Takizawa H. Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment. Front Immunol, 2016,7:502.
[39]	Salminen A, Kaarniranta K, Kauppinen A. The role of myeloid-derived suppressor cells (MDSC) in the inflammaging process. Ageing Res Rev, 2018,48:1-10.
[40]	Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature, 2014,505(7483):327-334.
[41]	Singh L, Brennan TA, Russell E, Kim JH, Chen QJ, Brad Johnson F, Pignolo RJ. Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage. Bone, 2016,85:29-36.
[42]	Shafat MS, Oellerich T, Mohr S, Robinson SD, Edwards DR, Marlein CR, Piddock RE, Fenech M, Zaitseva L, Abdul-Aziz A, Turner J, Watkins JA, Lawes M, Bowles KM, Rushworth SA. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood, 2017,129(10):1320-1332.
[43]	Gur-Cohen S, Itkin T, Chakrabarty S, Graf C, Kollet O, Ludin A, Golan K, Kalinkovich A, Ledergor G, Wong E, Niemeyer E, Porat Z, Erez A, Sagi I, Esmon CT, Ruf W, Lapidot T. Corrigendum: PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells. Nat Med, 2016,22(4):446.
[44]	Lacava G, Laus F, Amaroli A, Marchegiani A, Censi R, Di Martino P, Yanagawa T, Sabbieti MG, Agas D. P62 deficiency shifts mesenchymal/stromal stem cell commitment toward adipogenesis and disrupts bone marrow homeostasis in aged mice. J Cell Physiol, 2019,234(9):16338-16347.
[45]	Stauder R, Valent P, Theurl I. Anemia at older age: etiologies, clinical implications, and management. Blood, 2018,131(5):505-514.
[46]	Yacoub MF, Ferwiz HF, Said F. Effect of interleukin and hepcidin in anemia of chronic Diseases. Anemia, 2020,2020:3041738.
[47]	van Zeventer IA, de Graaf AO, Wouters HJCM, van der Reijden BA, van der Klauw MM, de Witte T, Jonker MA, Malcovati L, Jansen JH, Huls G. Mutational spectrum and dynamics of clonal hematopoiesis in anemia of older individuals. Blood, 2020,135(14):1161-1170.
[48]	Mattiucci D, Maurizi G, Leoni P, Poloni A. Aging- and senescence-associated changes of mesenchymal stromal cells in myelodysplastic syndromes. Cell Transplant. 2018,27(5):754-764.
[49]	Warren JT, Link DC. Clonal hematopoiesis and risk for hematologic malignancy. Blood, 2020,136(14):1599-1605.
[50]	Mei Y, Zhao B, Basiorka AA, Yang J, Cao L, Zhang J, List A, Ji P. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS. Leukemia, 2018,32(4):1023-1033.
[51]	Poloni A, Maurizi G, Mattiucci D, Amatori S, Fogliardi B, Costantini B, Mariani M, Mancini S, Olivieri A, Fanelli M, Leoni P. Overexpression of CDKN2B (p15INK4B) and altered global DNA methylation status in mesenchymal stem cells of high-risk myelodysplastic syndromes. Leukemia, 2014,28(11):2241-2244.
[52]	He HQ, Xu PL, Zhang XF, Liao M, Dong QY, Cong TT, Tang BX, Yang XX, Ye MQ, Chang YJ, Liu WH, Wang XW, Ju ZY, Wang JW. Aging-induced IL27Ra signaling impairs hematopoietic stem cells. Blood, 2020,136(2):183-198.
[53]	O'Connell RM, Rao DS. Microsized inflammaging protects stem cells. Blood, 2020,135(25):2204-2205.
[54]	Grants JM, Wegrzyn J, Hui T, O'Neill K, Shadbolt M, Knapp DJHF, Parker J, Deng Y, Gopal A, Docking TR, Fuller M, Li J, Boldin M, Eaves CJ, Hirst M, Karsan A. Altered microRNA expression links IL6 and TNF-induced inflammaging with myeloid malignancy in humans and mice. Blood, 2020,135(25):2235-2251.
[55]	Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science, 2019, 366(6465): eaan4673.
[56]	Hu YC, Hu HC, Lin SY, Chen XM. The role of DNA hydroxymethylation in the regulation of atherosclerosis. Hereditas (Beijing), 2020,42(7):632-640.
	胡颖楚, 胡豪畅, 林少沂, 陈晓敏. DNA羟甲基化调控动脉粥样硬化的研究进展. 遗传, 2020,42(7):632-640.
[57]	Saul D, Kosinsky RL. Epigenetics of aging and aging- associated diseases. Int J Mol Sci, 2021,22(1):401.
[58]	Hodjat M, Khan F, Saadat KASM. Epigenetic alterations in aging tooth and the reprogramming potential. Ageing Res Reviews, 2020,63:101140.
[59]	Mejia-Ramirez E, Geiger H, Florian MC. Loss of epigenetic polarity is a hallmark of hematopoietic stem cell aging. Hum Mol Genet, 2020,29(R2):R248-R254.

Metrics

Comments

www.chinagene.cn
备案号：京ICP备09063187号

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]

Progress on inflamm-aging in hematologic diseases

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 59

Related Articles 0

Recommended Articles

Metrics

Comments