Abstract
Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.
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References
Ferrucci L, Cavazzini C, Corsi A, Bartali B, Russo CR, Lauretani F, et al. Biomarkers of frailty in older persons. J Endocrinol Invest. 2002;25:10–15.
Fernandez-Garrido J, Ruiz-Ros V, Buigues C, Navarro-Martinez R, Cauli O. Clinical features of prefrail older individuals and emerging peripheral biomarkers: a systematic review. Arch Gerontol Geriatr. 2014;59:7–17.
Lippi G, Jansen-Duerr P, Vina J, Durrance-Bagale A, Abugessaisa I, Gomez-Cabrero D, et al. Laboratory biomarkers and frailty: presentation of the FRAILOMIC initiative. Clin Chem Lab Med. 2015;53:e253–255.
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–659.
Smith-Vikos T, Liu Z, Parsons C, Gorospe M, Ferrucci L, Gill TM, et al. A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA). Aging (Albany NY). 2016;8:2971–2987.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–156.
Espinoza SE, Hazuda HP. Frailty in older Mexican-American and European-American adults: is there an ethnic disparity? J Am Geriatr Soc. 2008;56:1744–1749.
Muller S, Rycak L, Winter P, Kahl G, Koch I, Rotter B. omiRas: a Web server for differential expression analysis of miRNAs derived from small RNA-Seq data. Bioinformatics. 2013;29:2651–2652.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.
Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37:1–13.
Akintola AA, van Heemst D. Insulin, aging, and the brain: mechanisms and implications. Front Endocrinol (Lausanne). 2015;6:13.
Burkewitz K, Zhang Y, Mair WB. AMPK at the nexus of energetics and aging. Cell Metab. 2014;20:10–25.
Martins R, Lithgow GJ, Link W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell. 2016;15:196–207.
Saenz-Cuesta M, Arbelaiz A, Oregi A, Irizar H, Osorio-Querejeta I, Munoz-Culla M, et al. Methods for extracellular vesicles isolation in a hospital setting. Front Immunol. 2015;6:50.
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Ipson, B.R., Fletcher, M.B., Espinoza, S.E. et al. Identifying Exosome-Derived MicroRNAs as Candidate Biomarkers of Frailty. J Frailty Aging 7, 100–103 (2018). https://doi.org/10.14283/jfa.2017.45
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DOI: https://doi.org/10.14283/jfa.2017.45