The involvement of serum exosomal miR-500-3p and miR-770-3p in aging: modulation by calorie restriction

// Eun Kyeong Lee 1 , Hyoung Oh Jeong 1 , Eun Jin Bang 1 , Chul Hong Kim 2 , Ji Young Mun 3,4 , Seulgi Noh 4 , Jeong-An Gim 5 , Dae Hyun Kim 1 , Ki Wung Chung 1 , Byung Pal Yu 6 and Hae Young Chung 1 1 Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea 2 Genomictree Inc., Daejeon, Republic of Korea 3 Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam-Si, Gyeonggi-Do, Republic of Korea 4 BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Seongnam-Si, Gyeonggi-Do, Republic of Korea 5 Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Republic of Korea 6 Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Correspondence to: Hae Young Chung, email: // Keywords : aging; calorie restriction; exosome; miR-500-3p; miR-770-3p; Gerotarget Received : September 04, 2017 Accepted : November 16, 2017 Published : December 24, 2017 Abstract Recent studies have shown a role for miRNAs in aging and age-related diseases, and the modulation of miRNA expression by diet attracts attention as a new therapeutic strategy. Here, we focused on identifying specific exosomal miRNAs derived from serum of aged rats and the effect of short-term calorie restriction (CR) on their expression. Exosomes from serum of young (7-month), old (22-month), and old-CR Sprague Dawley rats were isolated and characterized by transmission electron microscopy analyses, dynamic light scattering measurements, and Western blotting. A total of 12 significantly expressed miRNAs in serum exosomes of young and old rats were identified by next generation sequencing. After analysis of qRT-PCR, we found that miR-500-3p and miR-770-3p expression was significantly upregulated by aging and downregulated by CR. Furthermore, receiver operating characteristic (ROC) curve revealed that the selected miRNAs represented high accuracy in discriminating old rats from young rats. Finally, PANTHER analysis predicted selected miRNAs targets genes involved in Wnt/chemokines and cytokines -related inflammatory signaling pathway and function as transcription factor. In conclusion, our results suggest that the expression of serum exosomal miR-500-3p and miR-770-3p was significantly increased with aging, whereas these were decreased by CR, and age-/CR-modulated exosomal miR-500-3p and miR-770-3p could potentially be used as informative biomarkers candidates for aging.