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microRNA: Basic Science pp 213–230Cite as

Regulatory Roles of miRNAs in Aging

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 887))

Abstract

Aging is a biological process characterized by the progressive deterioration of physiological functions that occurs through the accumulation of macromolecular and cellular damage. This phenomenon impairs tissue function and is a risk factor for many disorders including cardiovascular disease, neurodegenerative disorders, and cancer. A recent study has enumerated nine cellular and molecular hallmarks that represent common denominators of aging and together determine the aging phenotype, highlighting the concept of aging plasticity. Among the multiple molecular mechanisms which may contribute to aging modulation, microRNAs (miRNAs) are raising enormous interest due to their ability to affect all the “Hallmarks of Aging.” In this chapter, we will focus on the description of the diverse functional roles of geromiRs, the large and growing subgroup of miRNAs implicated in aging. We will also address the molecular mechanisms underlying miRNA function in aging and discuss potential strategies for managing aging and extending longevity based on geromiR modulation.

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Abbreviations

DDR:

DNA damage response

IGF-1:

Insulin-like growth factor 1

References

  1. Vijg J, Campisi J. Puzzles, promises and a cure for ageing. Nature. 2008;454:1065–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kenyon CJ. The genetics of ageing. Nature. 2010;464:504–12.

    Article  CAS  PubMed  Google Scholar 

  3. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  CAS  PubMed  Google Scholar 

  5. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14:475–88.

    Article  CAS  PubMed  Google Scholar 

  6. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–39.

    Article  CAS  PubMed  Google Scholar 

  7. Ugalde AP, Espanol Y, Lopez-Otin C. Micromanaging aging with miRNAs: new messages from the nuclear envelope. Nucleus. 2011;2:549–55.

    Article  PubMed  Google Scholar 

  8. Boehm M, Slack F. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310:1954–7.

    Article  CAS  PubMed  Google Scholar 

  9. Kato M, Chen X, Inukai S, Zhao H, Slack FJ. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA. 2011;17:1804–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lucanic M, Graham J, Scott G, Bhaumik D, Benz CC, Hubbard A, Lithgow GJ, Melov S. Age-related micro-RNA abundance in individual C. elegans. Aging. 2013;5:394–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu N, Landreh M, Cao K, Abe M, Hendriks GJ, Kennerdell JR, Zhu Y, Wang LS, Bonini NM. The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature. 2012;482:519–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Simon AF, Shih C, Mack A, Benzer S. Steroid control of longevity in Drosophila melanogaster. Science. 2003;299:1407–10.

    Article  CAS  PubMed  Google Scholar 

  13. Vilmos P, Bujna A, Szuperak M, Havelda Z, Varallyay E, Szabad J, Kucerova L, Somogyi K, Kristo I, Lukacsovich T, Jankovics F, Henn L, Erdelyi M. Viability, longevity, and egg production of Drosophila melanogaster are regulated by the miR-282 microRNA. Genetics. 2013;195:469–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yin L, Sun Y, Wu J, Yan S, Deng Z, Wang J, Liao S, Yin D, Li G. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing. Neurobiol Aging. 2015;36:1037–44.

    Article  CAS  PubMed  Google Scholar 

  15. Li N, Bates DJ, An J, Terry DA, Wang E. Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain. Neurobiol Aging. 2011;32:944–55.

    Article  CAS  PubMed  Google Scholar 

  16. Kim JY, Park YK, Lee KP, Lee SM, Kang TW, Kim HJ, Dho SH, Kim SY, Kwon KS. Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle with aging. Aging. 2014;6:524–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bates DJ, Li N, Liang R, Sarojini H, An J, Masternak MM, Bartke A, Wang E. MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell. 2010;9:1–18.

    Article  CAS  PubMed  Google Scholar 

  18. Marino G, Ugalde AP, Fernandez AF, Osorio FG, Fueyo A, Freije JM, Lopez-Otin C. Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function. Proc Natl Acad Sci U S A. 2010;107:16268–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ugalde AP, Ramsay AJ, de la Rosa J, Varela I, Marino G, Cadinanos J, Lu J, Freije JM, Lopez-Otin C. Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53. EMBO J. 2011;30:2219–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, Yuan Y, Ning Z, Hu Y, Menzel C, Hu H, Lachmann M, Zeng R, Chen W, Khaitovich P. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 2010;20:1207–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Noren Hooten N, Fitzpatrick M, Wood 3rd WH, De S, Ejiogu N, Zhang Y, Mattison JA, Becker KG, Zonderman AB, Evans MK. Age-related changes in microRNA levels in serum. Aging. 2013;5:725–40.

    Article  PubMed  Google Scholar 

  22. Serna E, Gambini J, Borras C, Abdelaziz KM, Belenguer A, Sanchis P, Avellana JA, Rodriguez-Manas L, Vina J. Centenarians, but not octogenarians, up-regulate the expression of microRNAs. Sci Rep. 2012;2:961.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Simon LM, Edelstein LC, Nagalla S, Woodley AB, Chen ES, Kong X, Ma L, Fortina P, Kunapuli S, Holinstat M, McKenzie SE, Dong JF, Shaw CA, Bray PF. Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics. Blood. 2014;123:e37–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–94.

    Article  CAS  PubMed  Google Scholar 

  25. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6:214–30.

    Article  CAS  PubMed  Google Scholar 

  26. Cannell IG, Kong YW, Johnston SJ, Chen ML, Collins HM, Dobbyn HC, Elia A, Kress TR, Dickens M, Clemens MJ, Heery DM, Gaestel M, Eilers M, Willis AE, Bushell M. p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication. Proc Natl Acad Sci U S A. 2010;107:5375–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Okada N, Lin CP, Ribeiro MC, Biton A, Lai G, He X, Bu P, Vogel H, Jablons DM, Keller AC, Wilkinson JE, He B, Speed TP, He L. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression. Genes Dev. 2014;28:438–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kofman AV, Kim J, Park SY, Dupart E, Letson C, Bao Y, Ding K, Chen Q, Schiff D, Larner J, Abounader R. microRNA-34a promotes DNA damage and mitotic catastrophe. Cell Cycle. 2013;12:3500–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, Sanchez LM, Zhou Z, Rodriguez FJ, Stewart CL, Vega JA, Tryggvason K, Freije JM, Lopez-Otin C. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature. 2005;437:564–8.

    Article  CAS  PubMed  Google Scholar 

  30. Dallaire A, Garand C, Paquel ER, Mitchell SJ, de Cabo R, Simard MJ, Lebel M. Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging. Aging. 2012;4:636–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Francia S, Michelini F, Saxena A, Tang D, de Hoon M, Anelli V, Mione M, Carninci P, d’Adda di Fagagna F. Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature. 2012;488:231–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Liu B, Liu M, Wang J, Zhang X, Wang X, Wang P, Wang H, Li W, Wang Y. DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA damage via targeting p21/p27. Nucleic Acids Res. 2015;43:1626–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K. Modulation of microRNA processing by p53. Nature. 2009;460:529–33.

    Article  CAS  PubMed  Google Scholar 

  34. Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010;467:986–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.

    Article  CAS  PubMed  Google Scholar 

  36. Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D, Kaplunov JM, Bucci G, Dobreva M, Matti V, Beausejour CM, Herbig U, Longhese MP, d’Adda di Fagagna F. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol. 2012;14:355–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dinami R, Ercolani C, Petti E, Piazza S, Ciani Y, Sestito R, Sacconi A, Biagioni F, le Sage C, Agami R, Benetti R, Mottolese M, Schneider C, Blandino G, Schoeftner S. miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res. 2014;74:4145–56.

    Article  CAS  PubMed  Google Scholar 

  38. Kasiappan R, Shen Z, Tse AK, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, Bai W. 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J Biol Chem. 2012;287:41297–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Uziel O, Yosef N, Sharan R, Ruppin E, Kupiec M, Kushnir M, Beery E, Cohen-Diker T, Nordenberg J, Lahav M. The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis. Genomics. 2015;105:5–16.

    Article  CAS  PubMed  Google Scholar 

  40. Castro-Vega LJ, Jouravleva K, Liu WY, Martinez C, Gestraud P, Hupe P, Servant N, Albaud B, Gentien D, Gad S, Richard S, Bacchetti S, Londono-Vallejo A. Telomere crisis in kidney epithelial cells promotes the acquisition of a microRNA signature retrieved in aggressive renal cell carcinomas. Carcinogenesis. 2013;34:1173–80.

    Article  CAS  PubMed  Google Scholar 

  41. Sperka T, Wang J, Rudolph KL. DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 2012;13:579–90.

    Article  CAS  PubMed  Google Scholar 

  42. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lee J, Kemper JK. Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging. 2010;2:527–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A, Amati F, Vasa-Nicotera M, Ippoliti A, Novelli G, Melino G, Lauro R, Federici M. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation. 2009;120:1524–32.

    Article  CAS  PubMed  Google Scholar 

  45. Saunders LR, Sharma AD, Tawney J, Nakagawa M, Okita K, Yamanaka S, Willenbring H, Verdin E. miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues. Aging. 2010;2:415–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Marasa BS, Srikantan S, Martindale JL, Kim MM, Lee EK, Gorospe M, Abdelmohsen K. MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence. Aging. 2010;2:333–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Benetti R, Gonzalo S, Jaco I, Munoz P, Gonzalez S, Schoeftner S, Murchison E, Andl T, Chen T, Klatt P, Li E, Serrano M, Millar S, Hannon G, Blasco MA. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008;15:268–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Abe M, Naqvi A, Hendriks GJ, Feltzin V, Zhu Y, Grigoriev A, Bonini NM. Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila. Genes Dev. 2014;28:44–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Morimoto RI, Cuervo AM. Proteostasis and the aging proteome in health and disease. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1:S33–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Aguzzi A, O’Connor T. Protein aggregation diseases: pathogenicity and therapeutic perspectives. Nat Rev Drug Discov. 2010;9:237–48.

    Article  CAS  PubMed  Google Scholar 

  51. Persengiev S, Kondova I, Bontrop RE. Functional annotation of small noncoding RNAs target genes provides evidence for a deregulated ubiquitin-proteasome pathway in spinocerebellar ataxia type 1. J Nucleic Acids. 2012;2012:672536.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Tsimokha AS, Kulichkova VA, Karpova EV, Zaykova JJ, Aksenov ND, Vasilishina AA, Kropotov AV, Antonov A, Barlev NA. DNA damage modulates interactions between microRNAs and the 26S proteasome. Oncotarget. 2014;5:3555–67.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Fernandez AF, Lopez-Otin C. The functional and pathologic relevance of autophagy proteases. J Clin Invest. 2015;125:33–41.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Frankel LB, Wen J, Lees M, Hoyer-Hansen M, Farkas T, Krogh A, Jaattela M, Lund AH. microRNA-101 is a potent inhibitor of autophagy. EMBO J. 2011;30:4628–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Korkmaz G, le Sage C, Tekirdag KA, Agami R, Gozuacik D. miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy. 2012;8:165–76.

    Article  CAS  PubMed  Google Scholar 

  56. Rothe K, Lin H, Lin KB, Leung A, Wang HM, Malekesmaeili M, Brinkman RR, Forrest DL, Gorski SM, Jiang X. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood. 2014;123:3622–34.

    Article  CAS  PubMed  Google Scholar 

  57. Alvarez-Erviti L, Seow Y, Schapira AH, Rodriguez-Oroz MC, Obeso JA, Cooper JM. Influence of microRNA deregulation on chaperone-mediated autophagy and alpha-synuclein pathology in Parkinson’s disease. Cell Death Dis. 2013;4, e545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Menghini R, Casagrande V, Marino A, Marchetti V, Cardellini M, Stoehr R, Rizza S, Martelli E, Greco S, Mauriello A, Ippoliti A, Martelli F, Lauro R, Federici M. MiR-216a: a link between endothelial dysfunction and autophagy. Cell Death Dis. 2014;5, e1029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wang Q, Hu W, Lei M, Wang Y, Yan B, Liu J, Zhang R, Jin Y. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple ER stress-related chaperones during chronic oxidative stress. PLoS One. 2013;8, e84984.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Jung HJ, Suh Y. Regulation of IGF-1 signaling by microRNAs. Front Genet. 2014;5:472.

    PubMed  Google Scholar 

  61. Liang R, Khanna A, Muthusamy S, Li N, Sarojini H, Kopchick JJ, Masternak MM, Bartke A, Wang E. Post-transcriptional regulation of IGF1R by key microRNAs in long-lived mutant mice. Aging Cell. 2011;10:1080–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. La Rocca G, Badin M, Shi B, Xu SQ, Deangelis T, Sepp-Lorenzinoi L, Baserga R. Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway. J Cell Physiol. 2009;220:485–91.

    Article  PubMed  Google Scholar 

  63. Shan ZX, Lin QX, Fu YH, Deng CY, Zhou ZL, Zhu JN, Liu XY, Zhang YY, Li Y, Lin SG, Yu XY. Upregulated expression of miR-1/miR-206 in a rat model of myocardial infarction. Biochem Biophys Res Commun. 2009;381:597–601.

    Article  CAS  PubMed  Google Scholar 

  64. Wang XH, Qian RZ, Zhang W, Chen SF, Jin HM, Hu RM. MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol. 2009;36:181–8.

    Article  PubMed  Google Scholar 

  65. Olivieri F, Ahtiainen M, Lazzarini R, Pollanen E, Capri M, Lorenzi M, Fulgenzi G, Albertini MC, Salvioli S, Alen MJ, Kujala UM, Borghetti G, Babini L, Kaprio J, Sipila S, Franceschi C, Kovanen V, Procopio AD. Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs. Aging Cell. 2014;13:850–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Patel M, Gomez NC, McFadden AW, Moats-Staats BM, Wu S, Rojas A, Sapp T, Simon JM, Smith SV, Kaiser-Rogers K, Davis IJ. PTEN deficiency mediates a reciprocal response to IGFI and mTOR inhibition. Mol Cancer Res. 2014;12:1610–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bandiera S, Mategot R, Girard M, Demongeot J, Henrion-Caude A. MitomiRs delineating the intracellular localization of microRNAs at mitochondria. Free Radic Biol Med. 2013;64:12–9.

    Article  CAS  PubMed  Google Scholar 

  68. Rippo MR, Olivieri F, Monsurro V, Prattichizzo F, Albertini MC, Procopio AD. MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR-34a and miR-146a. Exp Gerontol. 2014;56:154–63.

    Article  CAS  PubMed  Google Scholar 

  69. Minones-Moyano E, Porta S, Escaramis G, Rabionet R, Iraola S, Kagerbauer B, Espinosa-Parrilla Y, Ferrer I, Estivill X, Marti E. MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet. 2011;20:3067–78.

    Article  CAS  PubMed  Google Scholar 

  70. Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol. 2011;192:547–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dellago H, Preschitz-Kammerhofer B, Terlecki-Zaniewicz L, Schreiner C, Fortschegger K, Chang MW, Hackl M, Monteforte R, Kuhnel H, Schosserer M, Gruber F, Tschachler E, Scheideler M, Grillari-Voglauer R, Grillari J, Wieser M. High levels of oncomiR-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan. Aging Cell. 2013;12:446–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Yang M, Haase AD, Huang FK, Coulis G, Rivera KD, Dickinson BC, Chang CJ, Pappin DJ, Neubert TA, Hannon GJ, Boivin B, Tonks NK. Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence. Mol Cell. 2014;55:782–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Overhoff MG, Garbe JC, Koh J, Stampfer MR, Beach DH, Bishop CL. Cellular senescence mediated by p16INK4A-coupled miRNA pathways. Nucleic Acids Res. 2014;42:1606–18.

    Article  CAS  PubMed  Google Scholar 

  74. Sene A, Khan AA, Cox D, Nakamura RE, Santeford A, Kim BM, Sidhu R, Onken MD, Harbour JW, Hagbi-Levi S, Chowers I, Edwards PA, Baldan A, Parks JS, Ory DS, Apte RS. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013;17:549–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Benhamed M, Herbig U, Ye T, Dejean A, Bischof O. Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol. 2012;14:266–75.

    Article  CAS  PubMed  Google Scholar 

  76. Gomez-Cabello D, Adrados I, Gamarra D, Kobayashi H, Takatsu Y, Takatsu K, Gil J, Palmero I. DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts. Aging Cell. 2013;12:923–31.

    Article  CAS  PubMed  Google Scholar 

  77. Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, Ho AD. Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One. 2008;3, e2213.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Yu JM, Wu X, Gimble JM, Guan X, Freitas MA, Bunnell BA. Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow. Aging Cell. 2011;10:66–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nishino J, Kim I, Chada K, Morrison SJ. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell. 2008;135:227–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Toledano H, D’Alterio C, Czech B, Levine E, Jones DL. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature. 2012;485:605–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Herrera-Merchan A, Cerrato C, Luengo G, Dominguez O, Piris MA, Serrano M, Gonzalez S. miR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal. Cell Cycle. 2010;9:3277–85.

    Article  CAS  PubMed  Google Scholar 

  82. Cheung TH, Quach NL, Charville GW, Liu L, Park L, Edalati A, Yoo B, Hoang P, Rando TA. Maintenance of muscle stem-cell quiescence by microRNA-489. Nature. 2012;482:524–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Brett JO, Renault VM, Rafalski VA, Webb AE, Brunet A. The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging. 2011;3:108–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kim YJ, Hwang SH, Lee SY, Shin KK, Cho HH, Bae YC, Jung JS. miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev. 2012;21:1749–60.

    Article  CAS  PubMed  Google Scholar 

  85. Shin KK, Kim YJ, Hong CP, Yang JW, Bae YC, Jung JS. Retracted article: miR-598 induces replicative senescence in human adipose tissue-derived mesenchymal stem cells via silent information regulator 1. Mol Cell Biochem. 2013;372(1–2):285.

    Article  CAS  Google Scholar 

  86. Dolezalova D, Mraz M, Barta T, Plevova K, Vinarsky V, Holubcova Z, Jaros J, Dvorak P, Pospisilova S, Hampl A. MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells. Stem Cells. 2012;30:1362–72.

    Article  CAS  PubMed  Google Scholar 

  87. Yu KR, Lee S, Jung JW, Hong IS, Kim HS, Seo Y, Shin TH, Kang KS. MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly targeting ZMPSTE24. J Cell Sci. 2013;126:5422–31.

    Article  CAS  PubMed  Google Scholar 

  88. Baixauli F, Lopez-Otin C, Mittelbrunn M. Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front Immunol. 2014;5:403.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014;14:195–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Boulias K, Horvitz HR. The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO. Cell Metab. 2012;15:439–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Shen Y, Wollam J, Magner D, Karalay O, Antebi A. A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science. 2012;338:1472–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Olivieri F, Rippo MR, Monsurro V, Salvioli S, Capri M, Procopio AD, Franceschi C. MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res Rev. 2013;12:1056–68.

    Article  CAS  PubMed  Google Scholar 

  93. Olivieri F, Rippo MR, Prattichizzo F, Babini L, Graciotti L, Recchioni R, Procopio AD. Toll like receptor signaling in “inflammaging”: microRNA as new players. Immun Ageing. 2013;10:11.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, Zanesi N, Crawford M, Ozer GH, Wernicke D, Alder H, Caligiuri MA, Nana-Sinkam P, Perrotti D, Croce CM. MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012;109:E2110–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Vora M, Shah M, Ostafi S, Onken B, Xue J, Ni JZ, Gu S, Driscoll M. Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan. PLoS Genet. 2013;9, e1003737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Dimmeler S, Nicotera P. MicroRNAs in age-related diseases. EMBO Mol Med. 2013;5:180–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gordon LB, Rothman FG, Lopez-Otin C, Misteli T. Progeria: a paradigm for translational medicine. Cell. 2014;156:400–7.

    Article  CAS  PubMed  Google Scholar 

  98. Pincus Z, Smith-Vikos T, Slack FJ. MicroRNA predictors of longevity in Caenorhabditis elegans. PLoS Genet. 2011;7:e1002306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Dr. Víctor Quesada for critical reading of the manuscript. Our work is supported by grants from Ministerio de Economía y Competitividad and Instituto de Salud Carlos III (RTICC), Spain. The Instituto Universitario de Oncología is supported by Obra Social Cajastur-Asturias. C.L.-O. is an Investigator of the Botin Foundation supported by Banco Santander through its Santander Universities Global Division.

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  1. Department of Molecular Biochemistry and Biology, University of Oveido, University Institute of Oncology, Oviedo, 33006, Spain

    Xurde M. Caravia & Carlos López-Otín

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  1. Xurde M. Caravia
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  2. Carlos López-Otín
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Correspondence to Carlos López-Otín .

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  1. Columbia University Medical Center, New York, New York, USA

    Gaetano Santulli

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Caravia, X.M., López-Otín, C. (2015). Regulatory Roles of miRNAs in Aging. In: Santulli, G. (eds) microRNA: Basic Science. Advances in Experimental Medicine and Biology, vol 887. Springer, Cham. https://doi.org/10.1007/978-3-319-22380-3_11

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