Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2020, Vol. 11 Issue (6) : 1585-1593     DOI: 10.14336/AD.2020.0309
Review Article |
Circular RNAs: Promising Biomarkers for Age-related Diseases
Yan-hong Pan1,2, Wei-peng Wu1,2, Xing-dong Xiong1,2,*
1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China
2Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang 524023, China.
Download: PDF(524 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases.

Keywords circRNAs      biomarker      aging      age-related diseases     
Corresponding Authors: Xiong Xing-dong   
About author:

These authors contributed equally to this work.

Just Accepted Date: 13 March 2020   Issue Date: 19 November 2020
E-mail this article
E-mail Alert
Articles by authors
Pan Yan-hong
Wu Wei-peng
Xiong Xing-dong
Cite this article:   
Pan Yan-hong,Wu Wei-peng,Xiong Xing-dong. Circular RNAs: Promising Biomarkers for Age-related Diseases[J]. Aging and disease, 2020, 11(6): 1585-1593.
URL:     OR
Figure 1.  The biogenesis and function of circular RNAs (circRNAs). CircRNAs can be classified into three types - exonic circRNAs (ecircRNAs), retained-intron circRNAs or EIciRNAs and intronic circRNAs (ciRNAs). Nuclear circRNAs can regulate parental gene transcription, while cytoplasmic circRNAs can act as miRNA sponges, transcriptional regulators, binding partners of proteins, or even translated into functional proteins.
DiseasesType of diseasescircRNAsExpressionBiological functionRefs.
Cardio-cerebrovascular diseaseHeart failurecircHRCRDownregulatedInhibits cardiac hypertrophy and heart failure by sponging miR-223[44]
Myocardial infarctioncircMFACRUpregulatedMediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression[47]
Cardiac senescencecircFoxo3UpregulatedPromotes cardiac senescence by arrest ID-1, E2F1, FAK, and HIF1a in the cytoplasm[18]
AtherosclerosiscircANRILDownregulatedControls ribosome biogenesis through binding to PES1 and modulates pathways of atherogenesis[45]
Coronary artery diseasehsa_circ_0124644UpregulatedPotential diagnostic biomarker of CAD in the peripheral blood[46]
hsa_circ_0001879UpregulatedA novel biomarker to diagnose CAD[48]
hsa_circ_0004104UpregulatedA novel biomarker to diagnose CAD[48]
StrokecircDLGAPDownregulatedAmeliorates ischemic stroke outcomes by targeting miR-143[49]
circHECTD1UpregulatedContributes to astrocyte activation and cerebral infarction by targeting miR-142-TIPARP[52]
circFUNDC1UpregulatedBiomarker for AIS diagnosis and prediction of outcomes[50]
circPDS5BUpregulatedBiomarker for AIS diagnosis and prediction of outcomes[50]
circCDC14AUpregulatedBiomarker for AIS diagnosis and prediction of outcomes[50]
NeurodegenerativeAlzheimer's diseaseciRS-7DownregulatedRegulates the expression of UBE2A by sponging miR-7[57]
diseaseParkinson’s diseaseciRS-7UpregulatedModulates the α-synuclein aggregation pattern in PD by targeting miR-7[59]
Multiple system atrophycircIQCKUpregulatedPotential biomarker for MSA[60]
circMAP4K3UpregulatedPotential biomarker for MSA[60]
circEFCAB11UpregulatedPotential biomarker for MSA[60]
circDTNAUpregulatedPotential biomarker for MSA[60]
circMCTP1UpregulatedPotential biomarker for MSA[60]
Amyotrophic lateral sclerosishsa_circ_0023919DownregulatedBlood biomarker for ALS[62]
hsa_circ_0063411UpregulatedBlood biomarker for ALS[62]
hsa_circ_0088036UpregulatedBlood biomarker for ALS[62]
CancerProstate cancercircCSNK1G3UpregulatedPromotes cell growth by interacting with miR-181[65]
circAMOTL1LDownregulatedFacilitates cell migration and invasion through binding miR-193a-5p[66]
circ_0044516UpregulatedPromotes prostate cancer cell proliferation and metastasis and serves as a potential biomarker[67]
Breast cancercircCNOT2UpregulatedA useful biomarker to choose the right type of therapy or to monitor breast cancer[68]
circEPSTI1UpregulatedRegulates cell proliferation and apoptosis of TNBC by targeting BCL11A via miR-4753/6809[69]
hsa_circ_001783UpregulatedCorrelates with tumor burden and serves as a novel prognostic and therapeutic target for breast cancer[70]
Colorectal cancercircKLDHC10UpregulatedPotential circulating biomarker for CRC diagnosis[56]
circ_0001178UpregulatedPromising biomarker for liver metastases from CRC[71]
circ_0000826UpregulatedPromising biomarker for liver metastases from CRC[71]
circCCDC66UpregulatedPredictive biomarker for CRC detection and prognosis[72]
DiabetesDiabeteshsa_circ_0054633UpregulatedCirculating diagnostic biomarker for pre-diabetes and T2DM[77]
hsa_circ_11783-2DownregulatedClosely related to T2DM and might be novel therapeutic targets in diabetes[78]
Diabetic retinopathycirc_0005015UpregulatedFacilitates retinal endothelial angiogenic function via sponging miR-519d-3p[80]
circHIPK3UpregulatedRegulates retinal endothelial cell function and
vascular dysfunction by sponging miR-30a
Diabetic cataractcircKMT2EUpregulatedInvolves in the pathogenesis of diabetic cataract[82]
Other diseasesRheumatoid arthritishsa_circ_0044235DownregulatedPotential diagnostic biomarker of RA patients[86]
OsteoporosiscircRUNX2DownregulatedPromotes the expression of osteogenic differentiation-related proteins by sponging miR-203[90]
circ_0002060UpregulatedPotential diagnostic biomarker and therapeutic target in osteoporosis[91]
Table 1  CircRNAs as potential biomarkers for age-related diseases.
[1] Zarrouk A, Vejux A, Mackrill J, O'Callaghan Y, Hammami M, O'Brien N, et al. (2014). Involvement of oxysterols in age-related diseases and ageing processes. Ageing Res Rev, 18:148-162.
[2] Dimmeler S, Nicotera P (2013). MicroRNAs in age-related diseases. EMBO Mol Med, 5:180-190.
[3] Bao Q, Pan J, Qi H, Wang L, Qian H, Jiang F, et al. (2014). Aging and age-related diseases--from endocrine therapy to target therapy. Mol Cell Endocrinol, 394:115-118.
[4] Noren Hooten N, Fitzpatrick M, Wood WH 3rd, De S, Ejiogu N, Zhang Y, et al. (2013). Age-related changes in microRNA levels in serum. Aging (Albany NY), 5:725-740.
[5] De A, Ghosh C (2017). Basics of aging theories and disease related aging-an overview. Pharma Tutor, 5:16-23.
[6] Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK (1976). Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A, 73:3852-3856.
[7] Hsu MT, Coca-Prados M (1979). Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature, 280:339-340.
[8] Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. (2013). Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 495:333-338.
[9] Suzuki H, Tsukahara T (2014). A view of pre-mRNA splicing from RNase R resistant RNAs. Int J Mol Sci, 15:9331-9342.
[10] Chen LL, Yang L (2015). Regulation of circRNA biogenesis. RNA Biol, 12:381-388.
[11] Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, et al. (2015). Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol, 22:256-264.
[12] Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, et al. (2013). Circular intronic long noncoding RNAs. Mol Cell, 51:792-806.
[13] Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. (2014). circRNA biogenesis competes with pre-mRNA splicing. Mol Cell, 56:55-66.
[14] Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. (2013). Natural RNA circles function as efficient microRNA sponges. Nature, 495:384-388.
[15] Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, et al. (2017). Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell, 66:22-37 e29.
[16] Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO (2013). Cell-type specific features of circular RNA expression. PLoS Genet, 9:e1003777.
[17] Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. (2013). Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19:141-157.
[18] Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, et al. (2017). Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J, 38:1402-1412.
[19] Yu AQ, Wang ZX, Wu W, Chen KY, Yan SR, Mao ZB (2019). Circular RNA CircCCNB1 sponges micro RNA-449a to inhibit cellular senescence by targeting CCNE2. Aging (Albany NY), 11:10220-10241.
[20] Panda AC, Grammatikakis I, Kim KM, De S, Martindale JL, Munk R, et al. (2017). Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res, 45:4021-4035.
[21] Haque S, Ames RM, Moore K, Pilling LC, Peters LL, Bandinelli S, et al. (2019). circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan. Geroscience.
[22] Kumar L, Shamsuzzama, Jadiya P, Haque R, Shukla S, Nazir A (2018). Functional Characterization of Novel Circular RNA Molecule, circzip-2 and Its Synthesizing Gene zip-2 in C. elegans Model of Parkinson's Disease. Mol Neurobiol, 55:6914-6926.
[23] Huang G, Li S, Yang N, Zou Y, Zheng D, Xiao T (2017). Recent progress in circular RNAs in human cancers. Cancer Lett, 404:8-18.
[24] Floris G, Zhang L, Follesa P, Sun T (2017). Regulatory Role of Circular RNAs and Neurological Disorders. Mol Neurobiol, 54:5156-5165.
[25] Liang D, Wilusz JE (2014). Short intronic repeat sequences facilitate circular RNA production. Genes Dev, 28:2233-2247.
[26] Starke S, Jost I, Rossbach O, Schneider T, Schreiner S, Hung LH, et al. (2015). Exon circularization requires canonical splice signals. Cell Rep, 10:103-111.
[27] Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L (2014). Complementary sequence-mediated exon circularization. Cell, 159:134-147.
[28] Cocquerelle C, Mascrez B, Hetuin D, Bailleul B (1993). Mis-splicing yields circular RNA molecules. Faseb j, 7:155-160.
[29] Barrett SP, Wang PL, Salzman J (2015). Circular RNA biogenesis can proceed through an exon-containing lariat precursor. Elife, 4:e07540.
[30] Wang Y, Wang Z (2015). Efficient backsplicing produces translatable circular mRNAs. RNA, 21:172-179.
[31] Zhang XO, Dong R, Zhang Y, Zhang JL, Luo Z, Zhang J, et al. (2016). Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res, 26:1277-1287.
[32] Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, et al. (2015). The RNA binding protein quaking regulates formation of circRNAs. Cell, 160:1125-1134.
[33] Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, et al. (2015). Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep, 10:170-177.
[34] Zaphiropoulos PG (1996). Circular RNAs from transcripts of the rat cytochrome P450 2C24 gene: correlation with exon skipping. Proc Natl Acad Sci U S A, 93:6536-6541.
[35] Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, et al. (2017). Translation of CircRNAs. Mol Cell, 66:9-21 e27.
[36] Yang Y, Gao X, Zhang M, Yan S, Sun C, Xiao F, et al. (2018). Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis. J Natl Cancer Inst, 110.
[37] Thomas LF, Saetrom P (2014). Circular RNAs are depleted of polymorphisms at microRNA binding sites. Bioinformatics, 30:2243-2246.
[38] Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, et al. (1993). Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell, 73:1019-1030.
[39] Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB (2016). Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res, 44:2846-2858.
[40] Yang ZG, Awan FM, Du WW, Zeng Y, Lyu J, Wu, et al. (2017). The Circular RNA Interacts with STAT3, Increasing Its Nuclear Translocation and Wound Repair by Modulating Dnmt3a and miR-17 Function. Mol Ther, 25:2062-2074.
[41] Perriman R, Ares M Jr, (1998). Circular mRNA can direct translation of extremely long repeating-sequence proteins in vivo. RNA, 4:1047-1054.
[42] Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, et al. (2017). Translation of CircRNAs. Mol Cell, 66:9-21.e27.
[43] Zhang M, Zhao K, Xu X, Yang Y, Yan S, Wei P, et al. (2018). A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat Commun, 9:4475-4475.
[44] Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, et al. (2016). A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J, 37:2602-2611.
[45] Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, et al. (2016). Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun, 7:12429.
[46] Zhao Z, Li X, Gao C, Jian D, Hao P, Rao L, et al. (2017). Peripheral blood circular RNA hsa_circ_0124644 can be used as a diagnostic biomarker of coronary artery disease. Sci Rep, 7:39918.
[47] Wang K, Gan TY, Li N, Liu CY, Zhou LY, Gao JN, et al. (2017). Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression. Cell Death Differ, 24:1111-1120.
[48] Wang L, Shen C, Wang Y, Zou T, Zhu H, Lu X, et al. (2019). Identification of circular RNA Hsa_circ_0001879 and Hsa_circ_0004104 as novel biomarkers for coronary artery disease. Atherosclerosis, 286:88-96.
[49] Bai Y, Zhang Y, Han B, Yang L, Chen X, Huang R, et al. (2018). Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood-Brain Barrier Integrity. J Neurosci, 38:32-50.
[50] Zuo L, Zhang L, Zu J, Wang Z, Han B, Chen B, et al. (2019). Circulating Circular RNAs as Biomarkers for the Diagnosis and Prediction of Outcomes in Acute Ischemic Stroke. Stroke:STROKEAHA119027348.
[51] Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. (1993). Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke, 24:35-41.
[52] Han B, Zhang Y, Zhang Y, Bai Y, Chen X, Huang R, et al. (2018). Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy, 14:1164-1184.
[53] Rybak-Wolf A, Stottmeister C, Glazar P, Jens M, Pino N, Giusti S, et al. (2015). Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell, 58:870-885.
[54] You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, et al. (2015). Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci, 18:603-610.
[55] Westholm JO, Miura P, Olson S, Shenker S, Joseph B, Sanfilippo P, et al. (2014). Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep, 9:1966-1980.
[56] Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, et al. (2015). Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res, 25:981-984.
[57] Lukiw WJ (2013). Circular RNA (circRNA) in Alzheimer's disease (AD). Front Genet, 4:307.
[58] Zhao Y, Alexandrov PN, Jaber V, Lukiw WJ (2016). Deficiency in the Ubiquitin Conjugating Enzyme UBE2A in Alzheimer's Disease (AD) is Linked to Deficits in a Natural Circular miRNA-7 Sponge (circRNA; ciRS-7). Genes(Basel), 7.
[59] Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM (2009). Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci U S A, 106:13052-13057.
[60] Chen BJ, Mills JD, Takenaka K, Bliim N, Halliday GM, Janitz M (2016). Characterization of circular RNAs landscape in multiple system atrophy brain. J Neurochem, 139:485-496.
[61] Hobson EV, Harwood CA, McDermott CJ, Shaw PJ (2016). Clinical aspects of motor neurone disease. Medicine, 44:552-556.
[62] Dolinar A, Koritnik B, Glavac D, Ravnik-Glavac M (2019). Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis. Mol Neurobiol, 56:8052-8062.
[63] Hansen J (1998). Common cancers in the elderly. Drugs Aging, 13:467-478.
[64] Yancik R (2005). Population aging and cancer: a cross-national concern. Cancer J, 11:437-441.
[65] Chen S, Huang V, Xu X, Livingstone J, Soares F, Jeon J, et al. (2019). Widespread and Functional RNA Circularization in Localized Prostate Cancer. Cell, 176:831-843 e822.
[66] Yang Z, Qu CB, Zhang Y, Zhang WF, Wang DD, Gao CC, et al. (2019). Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway. Oncogene, 38:2516-2532.
[67] Li T, Sun X, Chen L (2019). Exosome circ_0044516 promotes prostate cancer cell proliferation and metastasis as a potential biomarker. J Cell Biochem.
[68] Smid M, Wilting SM, Uhr K, Rodriguez-Gonzalez FG, de Weerd V, Prager-Van der Smissen WJC, et al. (2019). The circular RNome of primary breast cancer. Genome Res, 29:356-366.
[69] Chen B, Wei W, Huang X, Xie X, Kong Y, Dai D, et al. (2018). circEPSTI1 as a Prognostic Marker and Mediator of Triple-Negative Breast Cancer Progression. Theranostics, 8:4003-4015.
[70] Liu Z, Zhou Y, Liang G, Ling Y, Tan W, Tan L, et al. (2019). Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p. Cell Death Dis, 10:55.
[71] Xu H, Wang C, Song H, Xu Y, Ji G (2019). RNA-Seq profiling of circular RNAs in human colorectal Cancer liver metastasis and the potential biomarkers. Mol Cancer, 18:8.
[72] Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, et al. (2017). Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis. Cancer Res, 77:2339-2350.
[73] Sebesta EM, Anderson CB (2017). The Surgical Management of Prostate Cancer. Semin Oncol, 44:347-357.
[74] Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. (2016). Cancer statistics in China, 2015. CA Cancer J Clin, 66:115-132.
[75] DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A (2017). Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin, 67:439-448.
[76] Boitard C (2002). Insulin secretion in type 2 diabetes: clinical aspects. Diabetes Metab, 28:4s33-38.
[77] Zhao Z, Li X, Jian D, Hao P, Rao L, Li M (2016). Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus. Acta Diabetologica, 54:237-245.
[78] Li X, Zhao Z, Jian D, Li W, Tang H, Li M (2017). Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus. Diabetes Vasc Dis Res, 14:510-515.
[79] Sena CM, Pereira AM, Seica R (2013). Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim Biophys Acta, 1832:2216-2231.
[80] Zhang SJ, Chen X, Li CP, Li XM, Liu C, Liu BH, et al. (2017). Identification and Characterization of Circular RNAs as a New Class of Putative Biomarkers in Diabetes Retinopathy. Invest Ophthalmol Vis Sci, 58:6500-6509.
[81] Shan K, Liu C, Liu BH, Chen X, Dong R, Liu X, et al. (2017). Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus. Circulation, 136:1629-1642.
[82] Fan C, Liu X, Li W, Wang H, Teng Y, Ren J, et al. (2019). Circular RNA circ KMT2E is up-regulated in diabetic cataract lenses and is associated with miR-204-5p sponge function. Gene, 710:170-177.
[83] Wang W, Zhang Y, Zhu B, Duan T, Xu Q, Wang R, et al. (2015). Plasma microRNA expression profiles in Chinese patients with rheumatoid arthritis. Oncotarget, 6:42557-42568.
[84] Hruskova V, Jandova R, Vernerova L, Mann H, Pecha O, Prajzlerova K, et al. (2016). MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis. Arthritis Res Ther, 18:124.
[85] Goekoop-Ruiterman YP, Huizinga TW (2010). Rheumatoid arthritis: can we achieve true drug-free remission in patients with RA? Nat Rev Rheumatol, 6:68-70.
[86] Luo Q, Zhang L, Li X, Fu B, Deng Z, Qing C, et al. (2018). Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis. Clin Exp Immunol, 194:118-124.
[87] Zheng F, Yu X, Huang J, Dai Y (2017). Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology. Mol Med Rep, 16:8029-8036.
[88] Teitelbaum SL (2000). Bone resorption by osteoclasts. Science, 289:1504-1508.
[89] Coleman RE (2011). Bone cancer in 2011: Prevention and treatment of bone metastases. Nat Rev Clin Oncol, 9:76-78.
[90] Yin Q, Wang J, Fu Q, Gu S, Rui Y (2018). CircRUNX2 through has-miR-203 regulates RUNX2 to prevent osteoporosis. J Cell Mol Med, 22:6112-6121.
[91] Huang Y, Xie J, Li E (2019). Comprehensive circular RNA profiling reveals circ_0002060 as a potential diagnostic biomarkers for osteoporosis. J Cell Biochem, 120:15688-15694.
[92] Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C (2005). Exosomal-like vesicles are present in human blood plasma. Int Immunol, 17:879-887.
[93] Hoorn EJ, Pisitkun T, Zietse R, Gross P, Frokiaer J, Wang NS, et al. (2005). Prospects for urinary proteomics: exosomes as a source of urinary biomarkers. Nephrology (Carlton), 10:283-290.
[1] Weili Li,Zhifeng Qi,Huining Kang,Xuzhen Qin,Haiqing Song,Xueqin Sui,Yi Ren,Xunming Ji,Qingfeng Ma,Ke Jian Liu. Serum Occludin as a Biomarker to Predict the Severity of Acute Ischemic Stroke, Hemorrhagic Transformation, and Patient Prognosis[J]. Aging and disease, 2020, 11(6): 1395-1406.
[2] Yan Zhao,Jun-Kun Zhan,Youshuo Liu. A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease[J]. Aging and disease, 2020, 11(6): 1594-1607.
[3] Yaping Shao,Yang Ouyang,Tianbai Li,Xinyao Liu,Xiaojiao Xu,Song Li,Guowang Xu,Weidong Le. Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer’s Disease[J]. Aging and disease, 2020, 11(6): 1459-1470.
[4] Anwen Shao,Danfeng Lin,Lingling Wang,Sheng Tu,Cameron Lenahan,Jianmin Zhang. Oxidative Stress at the Crossroads of Aging, Stroke and Depression[J]. Aging and disease, 2020, 11(6): 1537-1566.
[5] Preeti Gupta,Ryan Eyn Kidd Man,Eva K Fenwick,Amudha Aravindhan,Alfred TL Gan,Sahil Thakur,Bao Lin Pauline Soh,Joanne M Wood,Alex A Black,Angelique Chan,David Ng,Teoh Khim Hean,Edwin Goh,Chong Foong-Fong Mary,Jenny Loo,Ciaran Gerard Forde,Charumathi Sabanayagam,Ching-Yu Cheng,Tien Yin Wong,Ecosse L Lamoureux. Rationale and Methodology of The PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study [PIONEER][J]. Aging and disease, 2020, 11(6): 1444-1458.
[6] Rodrigo Urbina-Varela,María Inés Soto-Espinoza,Romina Vargas,Luis Quiñones,Andrea del Campo. Influence of BDNF Genetic Polymorphisms in the Pathophysiology of Aging-related Diseases[J]. Aging and disease, 2020, 11(6): 1513-1526.
[7] Alexey Moskalev,Ilia Stambler,Calogero Caruso. Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience[J]. Aging and disease, 2020, 11(6): 1363-1373.
[8] Zhang Xinmu,Li Lin. The Significance of 8-oxoGsn in Aging-Related Diseases[J]. Aging and disease, 2020, 11(5): 1329-1338.
[9] Li Tan,Thomas C Register,Raghunatha R Yammani. Age-Related Decline in Expression of Molecular Chaperones Induces Endoplasmic Reticulum Stress and Chondrocyte Apoptosis in Articular Cartilage[J]. Aging and disease, 2020, 11(5): 1091-1102.
[10] Yuejia Ding,Yuan Wang,Wanqin Zhang,Qiujin Jia,Xiaoling Wang,Yanyang Li,Shichao Lv,Junping Zhang. Roles of Biomarkers in Myocardial Fibrosis[J]. Aging and disease, 2020, 11(5): 1157-1174.
[11] Lijun Zhao,Jianzhong Cao,Kexin Hu,Xiaodong He,Dou Yun,Tanjun Tong,Limin Han. Sirtuins and their Biological Relevance in Aging and Age-Related Diseases[J]. Aging and disease, 2020, 11(4): 927-945.
[12] Allen Caobi,Rajib Kumar Dutta,Luis D Garbinski,Maria Esteban-Lopez,Yasemin Ceyhan,Mickensone Andre,Marko Manevski,Chet Raj Ojha,Jessica Lapierre,Sneham Tiwari,Tiyash Parira,Nazira El-Hage. The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy[J]. Aging and disease, 2020, 11(4): 895-915.
[13] Tian Li,Nan Mu,Yue Yin,Lu Yu,Heng Ma. Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases[J]. Aging and disease, 2020, 11(4): 967-977.
[14] Asish K Ghosh. p300 in Cardiac Development and Accelerated Cardiac Aging[J]. Aging and disease, 2020, 11(4): 916-926.
[15] Alan R Hipkiss. COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?[J]. Aging and disease, 2020, 11(4): 737-741.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd