Abstract
Aging has been considered to be the most important non-modifiable risk factor for stroke and death. Changes in circulation factors in the systemic environment, cellular senescence and artery hypertension during human ageing have been investigated. Exosomes are nanosize membrane vesicles that can regulate target cell functions via delivering their carried bioactive molecules (e.g. protein, mRNA, and microRNAs). In the central nervous system, exosomes and exosomal microRNAs play a critical role in regulating neurovascular function and are implicated in stroke initiation and progression. MicroRNAs are small non-coding RNAs that have been reported to play critical roles in various biological processes. Recently, evidence has shown that microRNAs are packaged into exosomes and can be secreted into the systemic and tissue environment. Circulating microRNAs participate in cellular senescence and contribute to age-associated stroke. Here, we provide an overview of current knowledge on exosomes and their carried microRNAs in the regulation of cellular and organismal ageing processes, demonstrating the potential role of exosomes and their carried microRNAs in age-associated stroke.
Keywords: Exosomes, microRNAs, age, stroke, neurovascular unit, neural stem cells.
Graphical Abstract
[http://dx.doi.org/10.3389/fnins.2018.00811] [PMID: 30459547]
[http://dx.doi.org/10.1097/01.WCB.0000071883.63724.A7] [PMID: 12843788]
[http://dx.doi.org/10.1161/01.STR.0000158923.19956.73] [PMID: 15746452]
[http://dx.doi.org/10.1016/j.pharmthera.2008.09.002] [PMID: 18930078]
[http://dx.doi.org/10.1016/j.jgg.2014.08.001] [PMID: 25269674]
[http://dx.doi.org/10.1007/s12035-016-0347-8] [PMID: 28168424]
[http://dx.doi.org/10.1016/j.conb.2019.01.006] [PMID: 30743177]
[http://dx.doi.org/10.1016/j.cell.2016.01.043] [PMID: 26967288]
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124630] [PMID: 25292428]
[http://dx.doi.org/10.1371/journal.pone.0067554] [PMID: 23844026]
[http://dx.doi.org/10.1002/jcb.29130] [PMID: 31219202]
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[http://dx.doi.org/10.3390/ijms160921294] [PMID: 26370963]
[http://dx.doi.org/10.1016/bs.pmbts.2016.12.013] [PMID: 28253991]
[http://dx.doi.org/10.1161/CIR.0000000000000659] [PMID: 30700139]
[http://dx.doi.org/10.1016/S1474-4422(03)00266-7] [PMID: 12849300]
[http://dx.doi.org/10.1023/A:1025639203283] [PMID: 14561047]
[http://dx.doi.org/10.1007/s40266-014-0212-2] [PMID: 25212952]
[http://dx.doi.org/10.1097/01.rmr.0000175131.63152.53] [PMID: 16041286]
[http://dx.doi.org/10.1016/0197-4580(96)00005-X] [PMID: 8832624]
[http://dx.doi.org/10.1093/cercor/10.5.464] [PMID: 10847596]
[http://dx.doi.org/10.1016/j.neuron.2009.08.039] [PMID: 19840553]
[http://dx.doi.org/10.1016/j.mad.2020.111312] [PMID: 32663480]
[http://dx.doi.org/10.1016/j.expneurol.2010.04.010] [PMID: 20406636]
[http://dx.doi.org/10.1002/ana.21798] [PMID: 20186857]
[http://dx.doi.org/10.1016/S0197-4580(02)00063-5] [PMID: 12493559]
[http://dx.doi.org/10.1016/S0304-3940(02)01177-1] [PMID: 12531457]
[http://dx.doi.org/10.1161/STROKEAHA.107.507251] [PMID: 18451350]
[http://dx.doi.org/10.1016/j.jacc.2004.12.074] [PMID: 15862416]
[http://dx.doi.org/10.1007/s00395-008-0742-z] [PMID: 18704258]
[http://dx.doi.org/10.1016/S0278-5846(02)00306-8] [PMID: 12502029]
[http://dx.doi.org/10.3389/fimmu.2017.01058] [PMID: 28912780]
[http://dx.doi.org/10.1159/000486356] [PMID: 29339666]
[http://dx.doi.org/10.1007/s12015-020-10064-z] [PMID: 33170433]
[http://dx.doi.org/10.3389/fnagi.2019.00301] [PMID: 31780917]
[http://dx.doi.org/10.1161/01.RES.0000269183.13937.e8] [PMID: 17478731]
[http://dx.doi.org/10.1186/s12974-020-01833-1] [PMID: 32429999]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14971] [PMID: 32895017]
[http://dx.doi.org/10.1016/S0140-6736(16)31134-5]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06651.x] [PMID: 10911963]
[http://dx.doi.org/10.1093/cvr/cvy009] [PMID: 29514201]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12655] [PMID: 31203728]
[http://dx.doi.org/10.1161/01.RES.0000020401.61826.EA] [PMID: 12065318]
[http://dx.doi.org/10.1096/fj.02-1049fje] [PMID: 12709402]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.089409]
[http://dx.doi.org/10.1046/j.1365-2249.2000.01281.x] [PMID: 10931139]
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.11.002] [PMID: 17118371]
[http://dx.doi.org/10.14336/AD.2018.0324] [PMID: 31011483]
[http://dx.doi.org/10.1093/gerona/glr228] [PMID: 22219513]
[http://dx.doi.org/10.1152/physiolgenomics.00136.2003] [PMID: 15020720]
[http://dx.doi.org/10.2353/ajpath.2007.060708] [PMID: 17200210]
[http://dx.doi.org/10.1016/S0928-4680(01)00064-5] [PMID: 11476967]
[http://dx.doi.org/10.1007/s00401-018-1859-2] [PMID: 29752550]
[http://dx.doi.org/10.1161/01.CIR.0000147731.24444.4D] [PMID: 15505103]
[http://dx.doi.org/10.1152/ajpheart.00854.2003]
[http://dx.doi.org/10.2741/3064] [PMID: 18508570]
[http://dx.doi.org/10.1016/j.exger.2013.08.003] [PMID: 23948180]
[http://dx.doi.org/10.1016/j.exger.2014.01.015] [PMID: 24463049]
[http://dx.doi.org/10.1161/hh2001.097796] [PMID: 11597994]
[http://dx.doi.org/10.1161/01.RES.87.10.840] [PMID: 11073878]
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]
[http://dx.doi.org/10.1253/circj.CJ-08-1102]
[http://dx.doi.org/10.1515/cclm-2020-0601] [PMID: 32692694]
[http://dx.doi.org/10.1084/jem.192.12.1731] [PMID: 11120770]
[http://dx.doi.org/10.1161/CIRCRESAHA.111.300431] [PMID: 23409289]
[http://dx.doi.org/10.1152/ajpheart.00012.2008]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311378] [PMID: 30355080]
[http://dx.doi.org/10.3892/mmr.2017.6238] [PMID: 28259956]
[http://dx.doi.org/10.1161/01.HYP.37.2.529]
[http://dx.doi.org/10.1016/j.jnutbio.2011.08.008] [PMID: 22284404]
[PMID: 22585611]
[http://dx.doi.org/10.1016/j.bcp.2013.02.015] [PMID: 23422569]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.715847] [PMID: 18040029]
[http://dx.doi.org/10.1371/journal.pmed.1003282] [PMID: 32903262]
[http://dx.doi.org/10.4161/auto.28477]
[http://dx.doi.org/10.1016/S0140-6736(09)61460-4] [PMID: 19801098]
[http://dx.doi.org/10.1016/j.tig.2007.11.004] [PMID: 18192065]
[http://dx.doi.org/10.1089/ars.2012.4840] [PMID: 22870907]
[http://dx.doi.org/10.18632/aging.100667] [PMID: 25140379]
[http://dx.doi.org/10.1016/j.cell.2005.01.027] [PMID: 15734677]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.017513] [PMID: 27821539]
[http://dx.doi.org/10.1186/1750-1326-9-31] [PMID: 25152012]
[http://dx.doi.org/10.4161/auto.28477] [PMID: 24879151]
[http://dx.doi.org/10.1126/science.1201940] [PMID: 21868666]
[http://dx.doi.org/10.1096/fj.13-230904] [PMID: 23884427]
[http://dx.doi.org/10.1111/acel.12161] [PMID: 24119029]
[http://dx.doi.org/10.1016/S0047-6374(01)00223-8] [PMID: 11322993]
[http://dx.doi.org/10.32607/20758251-2018-10-1-4-14] [PMID: 29713514]
[http://dx.doi.org/10.3390/ijms20102547] [PMID: 31137607]
[http://dx.doi.org/10.1016/j.cell.2007.12.032] [PMID: 18267069]
[http://dx.doi.org/10.1016/j.cell.2008.03.038] [PMID: 18555777]
[http://dx.doi.org/10.1038/nrc2560] [PMID: 19132009]
[http://dx.doi.org/10.1126/science.1092556] [PMID: 15375259]
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[http://dx.doi.org/10.1038/sj.leu.2404296] [PMID: 16791265]
[http://dx.doi.org/10.1186/s13287-020-01761-0] [PMID: 32600449]
[http://dx.doi.org/10.1161/STROKEAHA.119.025371] [PMID: 31394992]
[http://dx.doi.org/10.1016/j.arr.2019.100979]
[http://dx.doi.org/10.3390/ijms21186894] [PMID: 32962207]
[http://dx.doi.org/10.3402/jev.v1i0.18396] [PMID: 24009886]
[http://dx.doi.org/10.1016/0092-8674(83)90040-5] [PMID: 6307529]
[http://dx.doi.org/10.1093/jb/mvj128] [PMID: 16877764]
[http://dx.doi.org/10.1586/epr.09.17] [PMID: 19489699]
[http://dx.doi.org/10.1038/ncb2000]
[http://dx.doi.org/10.1083/jcb.200911018] [PMID: 20404108]
[http://dx.doi.org/10.1091/mbc.e05-11-1054] [PMID: 16707569]
[http://dx.doi.org/10.3390/ijms19041227] [PMID: 29670015]
[http://dx.doi.org/10.1146/annurev-cellbio-101512-122326] [PMID: 25288114]
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[http://dx.doi.org/10.1016/j.jconrel.2015.06.029] [PMID: 26143224]
[http://dx.doi.org/10.1016/j.bcp.2011.02.011] [PMID: 21371441]
[http://dx.doi.org/10.3390/cells9091974] [PMID: 32859053]
[http://dx.doi.org/10.1002/jnr.24696] [PMID: 32725652]
[http://dx.doi.org/10.1186/s10020-020-00167-1] [PMID: 32410577]
[http://dx.doi.org/10.3390/ijms21061908] [PMID: 32168775]
[http://dx.doi.org/10.1016/j.tig.2011.03.005] [PMID: 21592610]
[http://dx.doi.org/10.1038/nature23282] [PMID: 28746310]
[http://dx.doi.org/10.1093/gerona/glu145] [PMID: 25165030]
[http://dx.doi.org/10.18632/aging.100603] [PMID: 24088671]
[http://dx.doi.org/10.1111/j.1474-9726.2010.00549.x] [PMID: 20089119]
[http://dx.doi.org/10.18632/aging.100371] [PMID: 22064828]
[http://dx.doi.org/10.1182/blood-2013-02-478925]
[http://dx.doi.org/10.1073/pnas.0801613105] [PMID: 18755897]
[http://dx.doi.org/10.4161/cc.9.14.12182] [PMID: 20603603]
[http://dx.doi.org/10.1038/cdd.2009.56] [PMID: 19461653]
[http://dx.doi.org/10.1152/ajpendo.00192.2010] [PMID: 20424141]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.864629] [PMID: 19786632]
[http://dx.doi.org/10.1038/onc.2009.497] [PMID: 20101223]
[http://dx.doi.org/10.1161/JAHA.117.007003] [PMID: 29018026]
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[http://dx.doi.org/10.1073/pnas.0707493105] [PMID: 18227515]
[http://dx.doi.org/10.1073/pnas.1107052108] [PMID: 21636785]
[http://dx.doi.org/10.1155/2016/6021394] [PMID: 28097140]
[http://dx.doi.org/10.1007/s11033-011-1241-0] [PMID: 21952822]
[http://dx.doi.org/10.1111/jch.12900] [PMID: 27550546]
[http://dx.doi.org/10.1016/j.arr.2014.03.005] [PMID: 24681293]
[http://dx.doi.org/10.1002/emmm.201201986] [PMID: 23339066]
[http://dx.doi.org/10.1016/j.exger.2011.10.004] [PMID: 22037549]
[http://dx.doi.org/10.1111/acel.12497] [PMID: 27325558]
[http://dx.doi.org/10.18632/aging.100489] [PMID: 23075628]
[http://dx.doi.org/10.18632/aging.100042] [PMID: 20148189]
[http://dx.doi.org/10.1093/intimm/dxu043] [PMID: 24648472]
[http://dx.doi.org/10.1016/j.mad.2012.09.004] [PMID: 23041385]
[http://dx.doi.org/10.18632/oncotarget.5899] [PMID: 26431329]
[http://dx.doi.org/10.7461/jcen.2014.16.1.11] [PMID: 24765608]
[http://dx.doi.org/10.1093/cvr/cvx197] [PMID: 29036612]
[http://dx.doi.org/10.1093/cvr/cvx248] [PMID: 29309533]
[http://dx.doi.org/10.3389/fgene.2017.00209] [PMID: 29312437]
[http://dx.doi.org/10.1371/journal.pone.0174108] [PMID: 28323879]
[http://dx.doi.org/10.2174/1573402113666170413094319] [PMID: 28412914]
[http://dx.doi.org/10.1371/journal.pone.0141512] [PMID: 26551255]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.303970] [PMID: 25323858]
[http://dx.doi.org/10.1152/physiolgenomics.00141.2011] [PMID: 22214600]
[http://dx.doi.org/10.2174/1874609811205020157] [PMID: 22894741]
[PMID: 22737264]
[http://dx.doi.org/10.2174/1567202613666161129112822] [PMID: 27897112]
[http://dx.doi.org/10.1096/fj.201701337RR] [PMID: 29570394]
[http://dx.doi.org/10.1002/jcb.27581] [PMID: 30272818]
[http://dx.doi.org/10.1182/blood-2007-03-078709] [PMID: 17536014]
[http://dx.doi.org/10.3727/096368911X627534] [PMID: 22455973]
[http://dx.doi.org/10.1038/srep14985] [PMID: 26447335]
[http://dx.doi.org/10.1038/cr.2017.62] [PMID: 28429770]
[http://dx.doi.org/10.1016/j.expneurol.2020.113411] [PMID: 32707150]
[http://dx.doi.org/10.1371/journal.pone.0163645] [PMID: 27661079]
[http://dx.doi.org/10.1161/CIRCRESAHA.106.141986] [PMID: 17478730]
[http://dx.doi.org/10.14336/AD.2019.0402] [PMID: 32010490]
[http://dx.doi.org/10.1371/journal.pone.0012519] [PMID: 20824140]
[http://dx.doi.org/10.1161/ATVBAHA.114.304877] [PMID: 25520518]
[http://dx.doi.org/10.1111/jpi.12631] [PMID: 31943334]
[http://dx.doi.org/10.1159/000445588]
[http://dx.doi.org/10.1038/s41419-019-1667-1] [PMID: 31142732]
[http://dx.doi.org/10.1111/jcmm.14060] [PMID: 30484954]
[http://dx.doi.org/10.7150/thno.37357] [PMID: 31660076]
[http://dx.doi.org/10.3389/fphys.2016.00692] [PMID: 28127288]