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

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.

Differential microRNAs expression profiles in liver from three different lifestyle modification mice models

“…Although there are some limitations in our study, such as a relatively small sample size, we confirmed some of the DE microRNAs and predicted targets with RT-qPCR. Differences of identified DE microRNAs do exist between our study and previous studies [23][24][25][26][27]…”

“…However, most of the microRNA profiling studies of exercise focus on circulating microRNAs or microRNAs in skeletal muscle and heart [9,14,16]. Although there are some studies on microRNA profiling in liver of HF or CR [23][24][25][26][27], however, there is little comprehensive knowledge regarding the similarities and differences of microRNAs profile in liver between these beneficial and detrimental lifestyles. Therefore, we examined the overall microRNAs expression in the liver of mice subjected to CR, EX and HF.…”

Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis

“…In addition to their regulatory role, many studies have shown that miRNAs are involved in aging and age-related diseases [48]. Further investigations are needed to explore the regulatory effect of specific miRNAs on gene expression in articular cartilage and other joint tissues and the potential use of miRNAs as therapeutic targets for age-related articular cartilage degeneration and OA [10].…”

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice

“…Marked overexpression of TFF3 was reported in HCC tissues in mice and humans and the expression was strongly correlated with HCC aggressiveness, being high in poorly differentiated tumors [41]. A 2-year 30% DR signif-icantly upregulated microRNA-125a-5p, which acts as a tumor suppressor through downregulating STAT3 [42]. STAT3 is activated by cytokines, insulin and the other growth factors, and oxidative stress [43], and persistent 30% DR drastically reduced these STAT3-activating factors and prevented liver tumorigenesis in the current study.…”