Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome.

Methods and Results: Older men (n = 31; 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg ⁻¹  day ⁻¹ ) or 2RDA (1.6 g kg ⁻¹  day ⁻¹ ) of protein for 10 weeks. Downregulation of five microRNAs (miR-125b-5p, -100-5p, -99a-5p, -23b-3p, and -203a) is observed following 2RDA with no changes in the RDA. In silico functional analysis highlights target gene enrichment in inflammation-related pathways. qPCR quantification of predicted inflammatory genes (TNFα, IL-8, IL-6, pTEN, PPP1CB, and HOXA1) in peripheral blood mononuclear cells shows increased expression following 2RDA diet (p ≤ 0.05).

Conclusion: The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.