The effects of different types of calorie restriction on microrna profile in mouse brain tissue

Ageing is a complex natural event characterized by deterioration of the physiological functions of the cell and organs. Ageing increases disease vulnerability such as cancer and neurodegenerative diseases, and age-related diseases are one of the leading cause of deaths in humans. However, the effects of ageing could be ameliorated by calorie restriction (CR) which is a noninvasive intervention methods against ageing and applied by limiting calorie intake by up to 40 percent without malnutrition. Studies have shown that CR increases longevity and reverses the effect of ageing. On the other hand, microRNAs (miRNA), small noncoding RNAs that regulate 30 percent of protein expression are reported to play important roles in ageing, age-related diseases and cancer. Although, there have been many studies in relation to the effects of CR and ageing the exact molecular mechanisms of this phenomenon is not clearly known. Therefore, the aim of the present thesis was 1) to study the effects of long term CR on miRNA profile in brain of aged mice and 2) to compare miRNA profiles in brain tissue of mice with and without mammary tumor development. For this purpose, 10 weeks old MMTV-TGFα mice were enrolled in AL, CCR (15 percent CR), or ICR (three weeks of AL, one week of 60 percent CR in a cyclic manner) groups. Brain tissues were collected at week 10 and 81/82 in healthy and MT developed mice and miRNA expressions were profiled. Lower MT incidence and higher survival rates were observed in the CCR group. Similarly, CCR application showed better results in brain protection and modulate additional protective effects by increasing expression of mmu-miR-713 compared to AL and ICR groups. In ageing, regulated expression of mmu-miR-184-3p and mmu-miR-351-5p by CR could exhibit anti-ageing effects and other miRNAs that were regulated by CCR also alleviate effects of ageing. In conclusion, CR could confer anti-ageing effects by regulating miRNA expression. In addition, MT development disturbs brain miRNA profile by regulating miRNAs that are important in neuronal survival and neuron interaction related pathways. In conclusion, protective effects CR in brain could be modulated by regulating miRNAs including mmu-miR-713 and other miRNAs.