Date Published: July 31, 2017
Publisher: Impact Journals LLC
Author(s): Kuldeep Makwana, Sonal Arvind Patel, Nikkhil Velingkaar, Jey Sabith Ebron, Girish C. Shukla, Roman V. Kondratov.
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.
Aging, a multifactorial process, is accompanied by the decay of many physiological systems and development of various age-associated pathologies such as cancer, osteoporosis, cardiovascular, and metabolic diseases [1–3]. The human population in developed countries in the world is aged, about 15% of the population in the USA will be older than 65 by the year 2020 . As a consequence of aging, the number of age-associated diseases grows, which leads to increased cost of health care . Therefore, the delay of aging and the increase of health span are important tasks of modern biomedical sciences . Calorie restriction (reduction of calorie intake without malnutrition) is a dietary paradigm, which is known to delay aging and reduce the risk of various age-related pathologies [7,8]. Beneficial effects of CR have been reported in various organisms from unicellular to mammals [9,10], yet the mechanism of CR is not well deciphered. Increased resistance to stress including oxidative stress, reduced metabolic rate, changes in insulin/IGF/TOR, and sirtuin signaling pathways have been reported and proposed as potential molecular mechanisms of CR [11–14]. Calorie restriction induced changes in gene expression were also proposed as a contributing factor [15,16]. CR can affect gene expression through multiple mechanisms, such as changes in chromatin modifications, mRNA transcription processing, and mRNA translation. Control of the expression of regulatory RNAs such as miRNAs is an important mechanism of gene expression regulation [17–21].