Abstract
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress translation or induce mRNA degradation of target transcripts through sequence-specific binding. miRNAs target hundreds of transcripts to regulate diverse biological pathways and processes, including aging. Many microRNAs are differentially expressed during aging, generating interest in their use as aging biomarkers and roles as regulators of the aging process. In the invertebrates Caenorhabditis elegans and Drosophila, a number of miRNAs have been found to both positive and negatively modulate longevity through canonical aging pathways. Recent studies have also shown that miRNAs regulate age-associated processes and pathologies in a diverse array of mammalian tissues, including brain, heart, bone, and muscle. The review will present an overview of these studies, highlighting the role of individual miRNAs as biomarkers of aging and regulators of longevity and tissue-specific aging processes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aalto AP, Nicastro IA, Broughton JP et al (2018) Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. PLoS Genet 14:e1007379. https://doi.org/10.1371/journal.pgen.1007379
Ameling S, Kacprowski T, Chilukoti RK et al (2015) Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. BMC Med Genomics 8:61. https://doi.org/10.1186/s12920-015-0136-7
Axtell MJ, Westholm JO, Lai EC (2011) Vive la différence: biogenesis and evolution of microRNAs in plants and animals. Genome Biol 12:221. https://doi.org/10.1186/gb-2011-12-4-221
Bartke A, Brown-Borg H (2004) Life extension in the dwarf mouse. Curr Top Dev Biol 63:189–225. https://doi.org/10.1016/S0070-2153(04)63006-7
Bates DJ, Li N, Liang R et al (2010) MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell 9:1–18. https://doi.org/10.1111/j.1474-9726.2009.00529.x
Beltrán-Sánchez H, Soneji S, Crimmins EM (2015) Past, present, and future of healthy life expectancy: figure 1. Cold Spring Harb Perspect Med 5:a025957. https://doi.org/10.1101/cshperspect.a025957
Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310:1954–1957. https://doi.org/10.1126/science.1115596
Boon RA, Iekushi K, Lechner S et al (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495:107–110. https://doi.org/10.1038/nature11919
Boskey AL, Imbert L (2017) Bone quality changes associated with aging and disease: a review. Ann N Y Acad Sci 1410:93–106. https://doi.org/10.1111/nyas.13572
Boulias K, Horvitz HR (2012) The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO. Cell Metab 15:439–450. https://doi.org/10.1016/J.CMET.2012.02.014
Bushati N, Cohen SM (2007) MicroRNA functions. Annu Rev Cell Dev Biol 23:175–205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
Chawla G, Deosthale P, Childress S et al (2016) A let-7-to-miR-125 MicroRNA switch regulates neuronal integrity and lifespan in Drosophila. PLoS Genet 12:e1006247. https://doi.org/10.1371/journal.pgen.1006247
Che H, Sun L-H, Guo F et al (2014) Expression of amyloid-associated miRNAs in both the forebrain cortex and hippocampus of middle-aged rat. Cell Physiol Biochem 33:11–22. https://doi.org/10.1159/000356646
Chen Y-W, Song S, Weng R et al (2014) Systematic study of Drosophila microRNA functions using a collection of targeted knockout mutations. Dev Cell 31:784–800. https://doi.org/10.1016/j.devcel.2014.11.029
Chen J, Zou Q, Lv D et al (2019) Comprehensive transcriptional profiling of porcine brain aging. Gene 693:1–9. https://doi.org/10.1016/J.GENE.2019.01.019
Crimmins EM (2015) Lifespan and healthspan: past, present, and promise. Gerontologist 55:901–911. https://doi.org/10.1093/geront/gnv130
da Costa JP, Vitorino R, Silva GM et al (2016) A synopsis on aging-theories, mechanisms and future prospects. Ageing Res Rev 29:90–112. https://doi.org/10.1016/j.arr.2016.06.005
Davis C, Dukes A, Drewry M et al (2017a) MicroRNA-183-5p increases with age in bone-derived extracellular vesicles, suppresses bone marrow stromal (stem) cell proliferation, and induces stem cell senescence. Tissue Eng Part A 23:1231–1240. https://doi.org/10.1089/ten.TEA.2016.0525
Davis HM, Pacheco-Costa R, Atkinson EG et al (2017b) Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging. Aging Cell 16:551–563. https://doi.org/10.1111/acel.12586
de Lencastre A, Pincus Z, Zhou K et al (2010) MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol 20:2159–2168. https://doi.org/10.1016/j.cub.2010.11.015
de Lucia C, Komici K, Borghetti G et al (2017) MicroRNA in cardiovascular aging and age-related cardiovascular diseases. Front Med 4:74. https://doi.org/10.3389/fmed.2017.00074
Dellago H, Bobbili MR, Grillari J (2017) MicroRNA-17-5p: at the crossroads of cancer and aging—a mini-review. Gerontology 63:20–28. https://doi.org/10.1159/000447773
Demontiero O, Vidal C, Duque G (2012) Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis 4:61–76. https://doi.org/10.1177/1759720X11430858
Drummond MJ, McCarthy JJ, Sinha M et al (2011) Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis. Physiol Genomics 43:595–603. https://doi.org/10.1152/physiolgenomics.00148.2010
Du WW, Yang W, Fang L et al (2014) miR-17 extends mouse lifespan by inhibiting senescence signaling mediated by MKP7. Cell Death Dis 5:e1355. https://doi.org/10.1038/cddis.2014.305
Du WW, Li X, Li T et al (2015) The microRNA miR-17-3p inhibits mouse cardiac fibroblast senescence by targeting Par4. J Cell Sci 128:293–304. https://doi.org/10.1242/jcs.158360
Duan L, Liu C, Hu J et al (2018) Epigenetic mechanisms in coronary artery disease: the current state and prospects. Trends Cardiovasc Med 28:311–319. https://doi.org/10.1016/J.TCM.2017.12.012
Elobeid A, Libard S, Leino M et al (2016) Altered Proteins in the Aging Brain. J Neuropathol Exp Neurol 75:316–325. https://doi.org/10.1093/jnen/nlw002
Epstein FH, Wei JY (1992) Age and the cardiovascular system. N Engl J Med 327:1735–1739. https://doi.org/10.1056/NEJM199212103272408
Esslinger SM, Schwalb B, Helfer S et al (2013) Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan. RNA Biol 10:1042–1056. https://doi.org/10.4161/rna.24810
Feng Q, Zheng S, Zheng J (2018) The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis. Biosci Rep. https://doi.org/10.1042/bsr20180453
Fenn AM, Smith KM, Lovett-Racke AE et al (2013) Increased micro-RNA 29b in the aged brain correlates with the reduction of insulin-like growth factor-1 and fractalkine ligand. Neurobiol Aging 34:2748–2758. https://doi.org/10.1016/j.neurobiolaging.2013.06.007
Finger F, Ottens F, Springhorn A et al (2019) Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signalling. Nat Metab 1:350–359. https://doi.org/10.1038/s42255-019-0033-z
Friedman DB, Johnson TE (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118:75–86
Fuggle N, Shaw S, Dennison E, Cooper C (2017) Sarcopenia. Best Pract Res Clin Rheumatol 31:218–242. https://doi.org/10.1016/j.berh.2017.11.007
Gendron CM, Pletcher SD (2017) MicroRNAs mir-184 and let-7 alter Drosophila metabolism and longevity. Aging Cell 16:1434–1438. https://doi.org/10.1111/acel.12673
Gupta SK, Foinquinos A, Thum S et al (2016) Preclinical development of a microRNA-based therapy for elderly patients with myocardial infarction. J Am Coll Cardiol 68:1557–1571. https://doi.org/10.1016/j.jacc.2016.07.739
Gurha P, Wang T, Larimore AH et al (2013) MicroRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR-nuclear hormone receptor transcription. PLoS One 8:e75882. https://doi.org/10.1371/journal.pone.0075882
Hamrick MW, Herberg S, Arounleut P et al (2010) The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice. Biochem Biophys Res Commun 400:379–383. https://doi.org/10.1016/j.bbrc.2010.08.079
Hanna J, Hossain GS, Kocerha J (2019) The potential for microRNA therapeutics and clinical research. Front Genet 10:478. https://doi.org/10.3389/fgene.2019.00478
Hedden T, Gabrieli JDE (2004) Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5:87–96. https://doi.org/10.1038/nrn1323
Hooten NN, Fitzpatrick M, Wood WH et al (2013) Age-related changes in microRNA levels in serum. Aging (Albany NY) 5:725–740. https://doi.org/10.18632/aging.100603
Hsieh Y-W, Chang C, Chuang C-F (2012) The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans. PLoS Genet 8:e1002864. https://doi.org/10.1371/journal.pgen.1002864
Hu Z, Klein JD, Mitch WE et al (2014) MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways. Aging (Albany NY) 6:160–175. https://doi.org/10.18632/aging.100643
Hu C-H, Sui B-D, Du F-Y et al (2017) miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice. Sci Rep 7:43191. https://doi.org/10.1038/srep43191
Huang Y, Qi Y, Du J-Q, Zhang D (2014) MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4. Expert Opin Ther Targets 18:1–11. https://doi.org/10.1517/14728222.2014.961424
Ibáñez-Ventoso C, Vora M, Driscoll M (2008) Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PLoS One 3:e2818. https://doi.org/10.1371/journal.pone.0002818
Inukai S, Slack F (2013) MicroRNAs and the genetic network in aging. J Mol Biol 425:3601–3608. https://doi.org/10.1016/j.jmb.2013.01.023
Inukai S, de Lencastre A, Turner M, Slack F (2012) Novel microRNAs differentially expressed during aging in the mouse brain. PLoS One 7:e40028. https://doi.org/10.1371/journal.pone.0040028
Isik M, Blackwell TK, Berezikov E et al (2016) MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans. Sci Rep 6:36766. https://doi.org/10.1038/srep36766
Jazbutyte V, Fiedler J, Kneitz S et al (2013) MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart. Age (Dordr) 35:747–762. https://doi.org/10.1007/s11357-012-9407-9
Jung HJ, Suh Y (2014) Circulating miRNAs in ageing and ageing-related diseases. J Genet Genomics 41(9):465–472. https://doi.org/10.1016/j.jgg.2014.07.003
Jung HJ, Lee K-P, Milholland B et al (2017) Comprehensive miRNA profiling of skeletal muscle and serum in induced and normal mouse muscle atrophy during aging. J Gerontol A Biol Sci Med Sci 72:1483–1491. https://doi.org/10.1093/gerona/glx025
Kato M, Slack FJ (2013) Ageing and the small, non-coding RNA world. Ageing Res Rev 12:429–435. https://doi.org/10.1016/j.arr.2012.03.012
Ke K, Sul O-J, Rajasekaran M, Choi H-S (2015) MicroRNA-183 increases osteoclastogenesis by repressing heme oxygenase-1. Bone 81:237–246. https://doi.org/10.1016/J.BONE.2015.07.006
Kennerdell JR, Liu N, Bonini NM (2018) MiR-34 inhibits polycomb repressive complex 2 to modulate chaperone expression and promote healthy brain aging. Nat Commun 9:4188. https://doi.org/10.1038/s41467-018-06592-5
Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512. https://doi.org/10.1038/nature08980
Kenyon C, Chang J, Gensch E et al (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464. https://doi.org/10.1038/366461a0
Khan SS, Singer BD, Vaughan DE (2017) Molecular and physiological manifestations and measurement of aging in humans. Aging Cell 16:624–633. https://doi.org/10.1111/acel.12601
Khanna A, Muthusamy S, Liang R et al (2011) Gain of survival signaling by down-regulation of three key miRNAs in brain of calorie-restricted mice. Aging (Albany NY) 3:223–236. https://doi.org/10.18632/aging.100276
Kiezun A, Artzi S, Modai S et al (2012) miRviewer: a multispecies microRNA homologous viewer. BMC Res Notes 5:92. https://doi.org/10.1186/1756-0500-5-92
Kim JY, Park Y-K, Lee K-P et al (2014) Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle with aging. Aging (Albany NY) 6:524–544. https://doi.org/10.18632/aging.100677
Kim J, Yoon H, Chung D-E et al (2016) miR-186 is decreased in aged brain and suppresses BACE1 expression. J Neurochem 137:436–445. https://doi.org/10.1111/jnc.13507
Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73. https://doi.org/10.1093/nar/gkt1181
Kumar S, Vijayan M, Bhatti JS, Reddy PH (2017) MicroRNAs as peripheral biomarkers in aging and age-related diseases. Prog Mol Biol Transl Sci 146:47–94. https://doi.org/10.1016/BS.PMBTS.2016.12.013
Lai P, Song Q, Yang C et al (2016) Loss of Rictor with aging in osteoblasts promotes age-related bone loss. Cell Death Dis 7:e2408. https://doi.org/10.1038/cddis.2016.249
Lee K-P, Shin YJ, Panda AC et al (2015) miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4. Genes Dev 29:1605–1617. https://doi.org/10.1101/gad.263574.115
Leggio L, Vivarelli S, L’Episcopo F et al (2017) microRNAs in parkinson’s disease: from pathogenesis to novel diagnostic and therapeutic approaches. Int J Mol Sci. https://doi.org/10.3390/ijms18122698
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by Adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20. https://doi.org/10.1016/J.CELL.2004.12.035
Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13:622–638. https://doi.org/10.1038/nrd4359
Li N, Bates DJ, An J et al (2011a) Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain. Neurobiol Aging 32:944–955. https://doi.org/10.1016/J.NEUROBIOLAGING.2009.04.020
Li X, Khanna A, Li N, Wang E (2011b) Circulatory miR34a as an RNA-based, noninvasive biomarker for brain aging. Aging (Albany NY) 3:985–1002. https://doi.org/10.18632/aging.100371
Li S-H, Guo J, Wu J et al (2013) miR-17 targets tissue inhibitor of metalloproteinase 1 and 2 to modulate cardiac matrix remodeling. FASEB J 27:4254–4265. https://doi.org/10.1096/fj.13-231688
Li C-J, Cheng P, Liang M-K et al (2015) MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest 125:1509–1522. https://doi.org/10.1172/JCI77716
Li D, Liu J, Guo B et al (2016) Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 7:10872. https://doi.org/10.1038/ncomms10872
Liang R, Khanna A, Muthusamy S et al (2011) Post-transcriptional regulation of IGF1R by key microRNAs in long-lived mutant mice. Aging Cell 10:1080–1088. https://doi.org/10.1111/j.1474-9726.2011.00751.x
Liu N, Landreh M, Cao K et al (2012) The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature 482:519–523. https://doi.org/10.1038/nature10810
Machida T, Tomofuji T, Ekuni D et al (2015) MicroRNAs in salivary exosome as potential biomarkers of aging. Int J Mol Sci 16:21294–21309. https://doi.org/10.3390/ijms160921294
Marty E, Liu Y, Samuel A et al (2017) A review of sarcopenia: enhancing awareness of an increasingly prevalent disease. Bone 105:276–286. https://doi.org/10.1016/J.BONE.2017.09.008
Meder B, Backes C, Haas J et al (2014) Influence of the confounding factors age and sex on microRNA profiles from peripheral blood. Clin Chem 60:1200–1208. https://doi.org/10.1373/clinchem.2014.224238
Mercken EM, Majounie E, Ding J et al (2013) Age-associated miRNA alterations in skeletal muscle from rhesus monkeys reversed by caloric restriction. Aging (Albany NY) 5:692–703. https://doi.org/10.18632/aging.100598
Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B (2004) Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-γ2 transcription factor and TGF-β/BMP signaling pathways. Aging Cell 3:379–389. https://doi.org/10.1111/j.1474-9728.2004.00127.x
Murray-Stewart TR, Woster PM, Casero RA (2016) Targeting polyamine metabolism for cancer therapy and prevention. Biochem J 473:2937–2953. https://doi.org/10.1042/BCJ20160383
North BJ, Sinclair DA (2012) The intersection between aging and cardiovascular disease. Circ Res 110:1097–1108. https://doi.org/10.1161/CIRCRESAHA.111.246876
Olivieri F, Bonafè M, Spazzafumo L et al (2014) Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells. Aging (Albany NY) 6:771–786. https://doi.org/10.18632/aging.100693
Pardo PS, Hajira A, Boriek AM, Mohamed JS (2017) MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle. Aging (Albany NY) 9:1012–1029. https://doi.org/10.18632/aging.101207
Peng Y, Croce CM (2016) The role of microRNAs in human cancer. Signal Transduct Target Ther 1:15004. https://doi.org/10.1038/sigtrans.2015.4
Persengiev SP, Kondova II, Bontrop RE (2012) The impact of MicroRNAs on brain aging and neurodegeneration. Curr Gerontol Geriatr Res 2012:359369. https://doi.org/10.1155/2012/359369
Pincus Z, Smith-Vikos T, Slack FJ (2011) MicroRNA predictors of longevity in Caenorhabditis elegans. PLoS Genet 7:e1002306. https://doi.org/10.1371/journal.pgen.1002306
Plotkin LI, Bellido T (2016) Osteocytic signalling pathways as therapeutic targets for bone fragility. Nat Rev Endocrinol 12:593–605. https://doi.org/10.1038/nrendo.2016.71
Quinlan S, Kenny A, Medina M et al (2017) MicroRNAs in neurodegenerative diseases. Int Rev Cell Mol Biol 334:309–343. https://doi.org/10.1016/BS.IRCMB.2017.04.002
Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet (Lond, Engl) 377:1276–1287. https://doi.org/10.1016/S0140-6736(10)62349-5
Ramanujam D, Sassi Y, Laggerbauer B, Engelhardt S (2016) Viral vector-based targeting of miR-21 in cardiac nonmyocyte cells reduces pathologic remodeling of the heart. Mol Ther 24:1939–1948. https://doi.org/10.1038/mt.2016.166
Redshaw Z, Sweetman D, Loughna PT (2014) The effects of age upon the expression of three miRNAs in muscle stem cells isolated from two different porcine skeletal muscles. Differentiation 88:117–123. https://doi.org/10.1016/J.DIFF.2014.12.001
Ripa R, Dolfi L, Terrigno M et al (2017) MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging. BMC Biol 15:9. https://doi.org/10.1186/s12915-017-0354-x
Rivas DA, Lessard SJ, Rice NP et al (2014) Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. FASEB J 28:4133–4147. https://doi.org/10.1096/fj.14-254490
Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222. https://doi.org/10.1038/nrd.2016.246
Sawada S, Akimoto T, Takahashi M et al (2014) Effect of aging and sex on circulating microRNAs in humans. Adv Aging Res 03:152–159. https://doi.org/10.4236/aar.2014.32023
Shao H, Yang L, Wang L et al (2018) MicroRNA-34a protects myocardial cells against ischemia–reperfusion injury through inhibiting autophagy via regulating TNFα expression. Biochem Cell Biol 96:349–354. https://doi.org/10.1139/bcb-2016-0158
Shih H, Lee B, Lee RJ, Boyle AJ (2011) The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol 57:9–17. https://doi.org/10.1016/J.JACC.2010.08.623
Simon AF, Shih C, Mack A, Benzer S (2003) Steroid control of longevity in Drosophila melanogaster. Science (80−) 299:1407–1410. https://doi.org/10.1126/science.1080539
Smith-Vikos T, Slack FJ (2012) MicroRNAs and their roles in aging. J Cell Sci 125:7–17. https://doi.org/10.1242/jcs.099200
Smith-Vikos T, de Lencastre A, Inukai S et al (2014) MicroRNAs mediate dietary-restriction-induced longevity through PHA-4/FOXA and SKN-1/Nrf transcription factors. Curr Biol 24:2238–2246. https://doi.org/10.1016/j.cub.2014.08.013
Smith-Vikos T, Liu Z, Parsons C et al (2016) A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA). Aging (Albany NY) 8:2971–2987. https://doi.org/10.18632/aging.101106
Soriano-Arroquia A, House L, Tregilgas L et al (2016) The functional consequences of age-related changes in microRNA expression in skeletal muscle. Biogerontology 17:641–654. https://doi.org/10.1007/s10522-016-9638-8
Sowell ER, Thompson PM, Toga AW (2004) Mapping changes in the human cortex throughout the span of life. Neurosci 10:372–392. https://doi.org/10.1177/1073858404263960
Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8:143–164. https://doi.org/10.1016/j.hfc.2011.08.011
Sun W, Zhao C, Li Y et al (2016) Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2:16015. https://doi.org/10.1038/celldisc.2016.15
Takeda T, Tanabe H (2016) Lifespan and reproduction in brain-specific miR-29-knockdown mouse. Biochem Biophys Res Commun 471:454–458. https://doi.org/10.1016/j.bbrc.2016.02.055
Ueda M, Sato T, Ohkawa Y, Inoue YH (2018) Identification of miR-305, a microRNA that promotes aging, and its target mRNAs in Drosophila. Genes Cells 23:80–93. https://doi.org/10.1111/gtc.12555
Ugalde AP, Ramsay AJ, de la Rosa J et al (2011) Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53. EMBO J 30:2219–2232. https://doi.org/10.1038/emboj.2011.124
Van Aelst LNL, Voss S, Carai P et al (2015) Osteoglycin prevents cardiac dilatation and dysfunction after myocardial infarction through infarct collagen strengthening. Circ Res 116:425–436. https://doi.org/10.1161/CIRCRESAHA.116.304599
van Almen GC, Verhesen W, van Leeuwen REW et al (2011) MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell 10:769–779. https://doi.org/10.1111/j.1474-9726.2011.00714.x
Verjans R, van Bilsen M, Schroen B (2017) MiRNA deregulation in cardiac aging and associated disorders. Int Rev Cell Mol Biol 334:207–263. https://doi.org/10.1016/BS.IRCMB.2017.03.004
Verma P, Augustine GJ, Ammar M-R et al (2015) A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity. Nat Neurosci 18:379–385. https://doi.org/10.1038/nn.3935
Villar AV, García R, Merino D et al (2013) Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients. Int J Cardiol 167:2875–2881. https://doi.org/10.1016/J.IJCARD.2012.07.021
Vilmos P, Bujna A, Szuperák M et al (2013) Viability, longevity, and egg production of Drosophila melanogaster are regulated by the miR-282 microRNA. Genetics 195:469–480. https://doi.org/10.1534/genetics.113.153585
Wang X, Guo B, Li Q et al (2013) miR-214 targets ATF4 to inhibit bone formation. Nat Med 19:93–100. https://doi.org/10.1038/nm.3026
Wang M, Qin L, Tang B (2019) MicroRNAs in Alzheimer’s disease. Front Genet 10:153. https://doi.org/10.3389/fgene.2019.00153
Weber JA, Baxter DH, Zhang S et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56:1733–1741. https://doi.org/10.1373/clinchem.2010.147405
Weilner S, Schraml E, Wieser M et al (2016) Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. Aging Cell 15:744–754. https://doi.org/10.1111/acel.12484
Wu S, Kim T-K, Wu X et al (2016) Circulating microRNAs and life expectancy among identical twins. Ann Hum Genet 80:247–256. https://doi.org/10.1111/ahg.12160
Yang J, Chen D, He Y et al (2013a) MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. Age (Omaha) 35:11–22. https://doi.org/10.1007/s11357-011-9324-3
Yang N, Wang G, Hu C et al (2013b) Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency–induced osteoporosis. J Bone Miner Res 28:559–573. https://doi.org/10.1002/jbmr.1798
Yang Y, Cheng H-W, Qiu Y et al (2015) MicroRNA-34a plays a key role in cardiac repair and regeneration following myocardial infarction. Circ Res 117:450–459. https://doi.org/10.1161/CIRCRESAHA.117.305962
Yin L, Sun Y, Wu J et al (2015) Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing. Neurobiol Aging 36:1037–1044. https://doi.org/10.1016/J.NEUROBIOLAGING.2014.11.001
Yuan J, Chen H, Ge D et al (2017) Mir-21 promotes cardiac fibrosis after myocardial infarction via targeting Smad7. Cell Physiol Biochem 42:2207–2219. https://doi.org/10.1159/000479995
Zacharewicz E, Della Gatta P, Reynolds J et al (2014) Identification of microRNAs linked to regulators of muscle protein synthesis and regeneration in young and old skeletal muscle. PLoS One 9:e114009. https://doi.org/10.1371/journal.pone.0114009
Zhang X, Zabinsky R, Teng Y et al (2011) MicroRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause. Proc Natl Acad Sci USA 108:17997–18002. https://doi.org/10.1073/pnas.1105982108
Zhang X, Azhar G, Wei JY (2012) The expression of microRNA and microRNA clusters in the aging heart. PLoS One 7:e34688. https://doi.org/10.1371/journal.pone.0034688
Zhang H, Yang H, Zhang C et al (2015) Investigation of microRNA expression in human serum during the aging process. J Gerontol Ser A 70:102–109. https://doi.org/10.1093/gerona/glu145
Zhang Y, Liu Y-J, Liu T et al (2016) Plasma microRNA-21 is a potential diagnostic biomarker of acute myocardial infarction. Eur Rev Med Pharmacol Sci 20:323–329
Zhao C, Sun W, Zhang P et al (2015a) miR-214 promotes osteoclastogenesis by targeting Pten/PI3 k/Akt pathway. RNA Biol 12:343–353. https://doi.org/10.1080/15476286.2015.1017205
Zhao W, Dong Y, Wu C et al (2015b) MiR-21 overexpression improves osteoporosis by targeting RECK. Mol Cell Biochem 405:125–133. https://doi.org/10.1007/s11010-015-2404-4
Zhou X, Xu H, Liu Z et al (2018) miR-21 promotes cardiac fibroblast-to-myofibroblast transformation and myocardial fibrosis by targeting Jagged1. J Cell Mol Med 22:3816–3824. https://doi.org/10.1111/jcmm.13654
Zovoilis A, Agbemenyah HY, Agis-Balboa RC et al (2011) microRNA-34c is a novel target to treat dementias. EMBO J 30:4299–4308. https://doi.org/10.1038/emboj.2011.327
Acknowledgements
This work was supported by National Human Genome Institute Grant T32HG000045, National Institutes of Health Grant 1R01AG057748, and a Beckman Young Investigator award from the Arnold and Mabel Beckman Foundation.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all the authors, the corresponding author states that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kinser, H.E., Pincus, Z. MicroRNAs as modulators of longevity and the aging process. Hum Genet 139, 291–308 (2020). https://doi.org/10.1007/s00439-019-02046-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-019-02046-0