Research Paper Volume 9, Issue 7 pp 1825—1843

Aging and calorie restriction regulate the expression of miR-125a-5p and its target genes Stat3, Casp2 and Stard13

Kuldeep Makwana 1, , Sonal Arvind Patel 1, , Nikkhil Velingkaar 1, , Jey Sabith Ebron 1, , Girish C. Shukla 1, , Roman V. Kondratov 1, ,

  • 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 ;
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Copyright: Makwana et al. This is an open‐access 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.


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.


miRNAs: MicroRNA; CR: Calorie Restriction; AL: Adlibitum; miR-125a-5p: mmu-miR-125a-5p; miR-145b: mmu-miR-145b; Casp2: Caspase2; WT: Wild Type; MUT: Mutant; NC: Negative Control.