Aging and calorie restriction regulate the expression of miR-125a-5p and its target genes Stat3, Casp2 and Stard13
Kuldeep Makwana1,,
Sonal Arvind Patel1,,
Nikkhil Velingkaar1,,
Jey Sabith Ebron1,,
Girish C. Shukla1,,
Roman V. Kondratov1,,
1 Center for Gene Regulation in Health and Disease and Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA
Received: June 10, 2017 Accepted: July 27, 2017 Published: July 31, 2017
Makwana K, Patel SA, Velingkaar N, Ebron JS, Shukla GC, Kondratov RV, . Aging and calorie restriction regulate the expression of miR-125a-5p and its target genes Stat3, Casp2 and Stard13. Aging (Albany NY). 2017; 9:1825-1843. https://doi.org/10.18632/aging.101270
Copyright: Makwana et al. This is an openâaccess article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Calorie restriction (CR) is a dietary intervention known to delay aging. In order, to understand molecular mechanisms of CR, we analyzed the expression of 983 MicroRNAs (miRNAs) in the liver of female mice after 2 years of 30% CR using micro-array. 16 miRNAs demonstrated significant changes in their expression upon CR in comparison with age-matched control. mmu-miR-125a-5p (miR-125a-5p) was significantly upregulated upon CR, and in agreement with this, the expression of mRNAs for its three predicted target genes: Stat3, Casp2, and Stard13 was significantly downregulated in the liver of CR animals. The expression of precursor miRNA for miR-125a-5p was also upregulated upon CR, which suggests its regulation at the level of transcription. Upon aging miR-125a-5p expression was downregulated while the expression of its target genes was upregulated. Thus, CR prevented age-associated changes in the expression of miR-125a-5p and its targets. We propose that miR-125a-5p dependent downregulation of Stat3, Casp2, and Stard13 contributes to the calorie restriction-mediated delay of aging.