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Beyond hormone levels, miRNAs are important regulators of metabolic changes associated with healthy aging. We hypothesized that GH deficiency in humans alters the abundance of circulating miRNAs and that a subset of those miRNAs may overlap with those found in GH\u2010deficient mice. In this study, subjects with untreated congenital isolated GH deficiency (IGHD; <jats:italic>n<\/jats:italic>\u00a0=\u00a023) and control subjects matched by age and sex (<jats:italic>n<\/jats:italic>\u00a0=\u00a023) were recruited and serum was collected for miRNA sequencing. Serum miRNAs from young (6\u00a0month) and old (22\u00a0month) Ames dwarf (df\/df) mice with GH deficiency and their WT littermates (<jats:italic>n<\/jats:italic>\u00a0=\u00a05\/age\/genotype group) were used for comparison. We observed 14 miRNAs regulated with a genotype by age effect and 19 miRNAs regulated with a genotype effect independent of age in serum of IGHD subjects. These regulated miRNAs are known for targeting pathways associated with longevity such as mTOR, insulin signaling, and FoxO. The aging function was overrepresented in IGHD individuals, mediated by hsa\u2010miR\u201031, hsa\u2010miR\u2010146b, hsa\u2010miR\u201030e, hsa\u2010miR\u2010100, hsa\u2010miR\u2010181b\u20102, hsa\u2010miR\u2010195, and hsa\u2010miR\u2010181b\u20101, which target the FoxO and mTOR pathways. Intriguingly, miR\u2010181b\u20105p, miR\u2010361\u20103p, miR\u2010144\u20103p, and miR\u2010155\u20105p were commonly regulated in the serum of humans and GH\u2010deficient mice. In vitro assays confirmed target genes for the main up\u2010regulated miRNAs, suggesting miRNAs regulated in IGHD individuals can regulate the expression of age\u2010related genes. These findings indicate that systemic miRNAs regulated in IGHD individuals target pathways involved in aging in both humans and mice.<\/jats:p>","DOI":"10.1111\/acel.13420","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T13:41:35Z","timestamp":1623505295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Circulating microRNA profile in humans and mice with congenital GH deficiency"],"prefix":"10.1111","volume":"20","author":[{"given":"Tatiana D.","family":"Saccon","sequence":"first","affiliation":[{"name":"Centro de Desenvolvimento Tecnol\u00f3gico Universidade Federal de Pelotas  Pelotas Brazil"},{"name":"Burnett School of Biomedical Sciences College of Medicine University of Central Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Schneider","sequence":"additional","affiliation":[{"name":"Faculdade de Nutri\u00e7\u00e3o Universidade Federal de Pelotas  Pelotas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindi G.","family":"Marinho","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Health Sciences Graduate Program Federal University of Sergipe  Aracaju Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allancer D. 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