自噬调控衰老的研究进展
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摘要
随着机体老化,组织器官可发生不可逆退行性改变,这些变化与疾病和死亡密切相关。自噬是细胞内一种重要的分解代谢过程,在维持细胞稳态和促进长寿中起重要作用,机体衰老后,其自噬调节能力也随之下降。本文综述了自噬与衰老相关疾病的关系,明确自噬调控衰老的相关分子机制可能为治疗衰老相关疾病提供新的靶点。
Irreversible degenerative changes occur in tissues and organs as the body ages,and these changes are closely associated with disease and death.Autophagy,an important catabolic process in cells,plays a significant role in maintaining cell homeostasis and promoting longevity.Regulatory capacity of autophagy declines after aging.In this paper,we reviewed the relationship between autophagy and aging-associated diseases,claiming that the molecular mechanism of regulation of the aging process by autophagy may provide a new target for the treatment of aging-associated diseases.
Irreversible degenerative changes occur in tissues and organs as the body ages,and these changes are closely associated with disease and death.Autophagy,an important catabolic process in cells,plays a significant role in maintaining cell homeostasis and promoting longevity.Regulatory capacity of autophagy declines after aging.In this paper,we reviewed the relationship between autophagy and aging-associated diseases,claiming that the molecular mechanism of regulation of the aging process by autophagy may provide a new target for the treatment of aging-associated diseases.
引文
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[2]Mishra P,Dauphinee AN,Ward C,et al.Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3eukaryotic kingdoms[J].Autophagy,2017,13(9):1556-1572.DOI:1080/15548627.2017.1339002.
[3]Papp D,Kovacs T,Billes V,et al.AUTEN-67,an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects[J].Autophagy,2016,12(2):273-286.DOI:10.1080/15548627.2015.1082023.
[4]Lapierre LR,Kumsta C,Sandri M,et al.Transcriptional and epigenetic regulation of autophagy in aging[J].Autophagy,2015,11(6):867-880.DOI:10.1080/15548627.2015.1034410.
[5]Oku M,Maeda Y,Kagohashi Y,et al.Evidence for ESCRT-and clathrin-dependent microautophagy[J].J Cell Biol,2017,216(10):3263-3274.DOI:10.1083/jcb.201611029.
[6]Gelino S,Hansen M.Autophagy-an emerging anti-aging mechanism[J].J Clin Exp Pathol,2012,(Suppl 4).pii:006.
[7]Huber TB,Edelstein CL,Hartleben B,et al.Emerging role of autophagy in kidney function,diseases and aging[J].Autophagy,2012,8(7):1009-1031.DOI:10.4161/auto.19821.
[8]Kim EN,Lim JH,Kim MY,et al.Resveratrol,an Nrf2 activator,ameliorates aging-related progressive renal injury[J].Aging,2018,10(1):83-99.DOI:10.18632/agibg.101361.
[9]Vandenbroucke A,Luyten FP,Flamaing J,et al.Pharmacological treatment of osteoporosis in the oldest old[J].Clin Interv Aging,2017,12:1065-1077.DOI:10.2147/CIA.S131023.
[10]Ikeda Y,Sciarretta S,Nagarajan N,et al.New insights into the role of mitochondrial dynamics and autophagy during oxidative stress and aging in the heart[J].Oxid Med Cell Longev,2014,2014:210934.DOI:10.1155/2014/210934.
[11]Linton PJ,Gurney M,Sengstock D,et al.This old heart:cardiac aging and autophagy[J].J Mol Cell Cardiol,2015,83:44-54.DOI:10.1016/j.yjmcc.2014.12.017.
[12]Jenwitheesuk A,Nopparat C,Mukda S,et al.Melatonin regulates aging and neurodegeneration through energy metabolism,epigenetics,autophagy and circadian rhythm pathways[J].Int J Mol Sci,2014,15(9):16848-16884.DOI:10.3390/ijms150916848.
[13]Shibuya Y,Chang CC,Huang LH,et al.Inhibiting ACAT1/SOAT1 in microglia stimulates autophagy-mediated lysosomal proteolysis and increases Aβ1-42 clearance[J].J Neurosci,2014,34(43):14484-14501.DOI:10.1523/JNEUROSCI.2567-14.2014.
[14]Spilman P,Podlutskaya N,Hart MJ,et al.Inhibition of m TOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease[J].PLoS One,2010,5(4):e9979.DOI:10.1371/journal.pone.0009979.
[15]Lakatta EG.So!What's aging?Is cardiovascular aging a disease?[J].J Mol Cell Cardiol,2015,83:1-13.DOI:10.1016/j.yjmcc.2015.04.005.
[16]Ren J,Yang L,Zhu L,et al.Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling:role of Sirt1-mediated autophagy regulation[J].Aging Cell,2017,16(5):976-987.DOI:10.1111/acel.12616.
[17]Eisenberg T,Abdellatif M,Schroeder S,et al.Cardioprotection and lifespan extension by the natural polyamine spermidine[J].Nat Med,2016,22(12):1428-1438.DOI:10.1038/nm.4222.
[18]LaRocca TJ,Gioscia-Ryan RA,Hearon CM,et al.The autophagy enhancer spermidine reverses arterial aging[J].Mech Ageing Dev,2013,134(7-8):314-320.DOI:10.1016/j.mad.2013.04.004.
[19]Wallace IJ,Worthington S,Felson DT,et al.Knee osteoarthritis has doubled in prevalence since the mid-20th century[J].Proc Natl Acad Sci USA,2017,114(35):9332-9336.DOI:10.1073/pnas.1703856114.
[20]Ganguly P,El-Jawhari JJ,Giannoudis PV,et al.Age-related changes in bone marrow mesenchymal stromal cells:a potential impact on osteoporosis and osteoarthritis development[J].Cell Transplant,2017,26(9):1520-1529.DOI:10.1177/0963689717721201.
[21]Hu J,Cui W,Ding W,et al.Globular adiponectin attenuated H2O2-induced apoptosis in rat chondrocytes by inducing autophagy through the AMPK/m TOR pathway[J].Cell Physiol Biochem,2017,43(1):367-382.DOI:10.1159/000480416.
[22]Wang X,Bonventre JV,Parrish AR.The aging kidney:increased susceptibility to nephrotoxicity[J].Int J Mol Sci,2014,15(9):15358-15376.DOI:10.3390/ijms150915358.
[23]Cui J,Bai XY,Shi S,et al.Age-related changes in the function of autophagy in rat kidneys[J].Age(Dordr),2012,34(2):329-339.DOI:10.1007/s11357-011-9237-1.
[24]Liu A,Guo E,Yang J,et al.Young plasma reverses agedependent alterations in hepatic function through the restoration of autophagy[J].Aging Cell,2018,17(1):e12708.DOI:10.1111/acel.12708.
[25]Sosulski ML,Gongora R,Danchuk S,et al.Deregulation of selective autophagy during aging and pulmonary fibrosis:the role of TGFβ1[J].Aging Cell,2015,14(5):774-783.DOI:10.1111/acel.12357.
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