Dietary restriction (DR) is believed to be one of the most promising approaches to extend life span of different animal species and to delay deleterious age-related physiological alterations and diseases. Among others, DR was shown to ameliorate acute kidney injury (AKI) and chronic kidney disease (CKD). However, to date, a comprehensive analysis of the mechanisms of the protective effect of DR specifically in kidney pathologies has not been carried out. The protective properties of DR are mediated by a range of signaling pathways associated with adaptation to reduced nutrient intake. The adaptation is accompanied by a number of metabolic changes, such as autophagy activation, metabolic shifts toward lipid utilization and ketone bodies production, improvement of mitochondria functioning, and decreased oxidative stress. However, some studies indicated that with age, the gain of DR-mediated positive remodeling gradually decreases. This may be an obstacle if we seek to translate the DR approach into a clinic for the treatment of kidney diseases as most patients with AKI and CKD are elderly. It is well known that aging is accompanied by impairments in a huge variety of organs and systems, such as hormonal regulation, stress sensing, autophagy and proteasomal activity, gene expression, and epigenome profile, increased damage to macromolecules and organelles including mitochondria. All these age-associated changes might be the reasons for the reduced protective potential of the DR during aging. We summarized the available mechanisms of DR-mediated nephroprotection and described ways to improve the effectiveness of this approach for an aged kidney.

Mitochondrial translation is a unique relic of the symbiotic origin of the organelle. Alterations of its components cause a number of severe human diseases. Hereby we report a study of mice devoid of Mettl15 mitochondrial 12S rRNA methyltransferase, responsible for the formation of m4C839 residue (human numbering). Homozygous Mettl15−/− mice appeared to be viable in contrast to other mitochondrial rRNA methyltransferase knockouts reported earlier. The phenotype of Mettl15−/− mice is much milder than that of other mutants of mitochondrial translation apparatus. In agreement with the results obtained earlier for cell cultures with an inactivated Mettl15 gene, we observed accumulation of the RbfA factor, normally associated with the precursor of the 28S subunit, in the 55S mitochondrial ribosome fraction of knockout mice. A lack of Mettl15 leads to a lower blood glucose level after physical exercise relative to that of the wild-type mice. Mettl15−/− mice demonstrated suboptimal muscle performance and lower levels of Cox3 protein synthesized by mitoribosomes in the oxidative soleus muscles. Additionally, we detected decreased learning capabilities in the Mettl15−/− knockout mice in the tests with both positive and negative reinforcement. Such properties make Mettl15−/− knockout mice a suitable model for mild mitochondriopathies.