Characterization in mice of novel genes involved in the evolutionarily conserved m...
| Grant number: | 18/11792-9 |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| Effective date (Start): | August 01, 2018 |
| Effective date (End): | July 31, 2021 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Cooperation agreement: | Innovation Fund Denmark |
| Principal Investigator: | Marcelo Alves da Silva Mori |
| Grantee: | Deisi Lilian Braga |
| Home Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM |
Abstract Dietary restriction extends lifespan across species from yeast to primates. The study of the nematode C. elegans - where multiple protocols of dietary restriction has been shown to prolong lifespan in overlapping yet not necessarily identical manners has led to the identification of multiple evolutionarily conserved pathways associated with aging and the mechanisms of dietary restriction. Some of these pathways, like the mTOR or the IGF1/Insulin pathways affect health span in higher vertebrates and mounting data point to a role of these pathways in human aging. Given its short lifespan (approx. 21 days), C. elegans represents an excellent model for the discovery of new genes involved in aging, especially when studied in context with vertebrates. In worms, nicotinamide riboside and methionine restriction have been shown to prolong lifespan. The former is dependent on the worm sirtuin homolog SIR-2.13 while the latter is dependent on S-Adenosyl Methionine Synthetase (SAMS-1). More importantly, we found that lifespan extension exerted by dietary restriction, methionine restriction or increased NAD levels requires functionally active Dicer in C. elegans, thus indicating that these dietary interventions interact in a Dicer dependent manner to confer their beneficial effects. We therefore propose that dietary restriction can be mimicked by modifications of specific nutrient components in the diet. Like dietary restriction, these interventions depend on Dicer and other important metabolic genes to exert their beneficial effects. Understanding how these genes and the diets interact in the worm could therefore teach us more about their effects on higher vertebrates. To select evolutionarily conserved genes involved in the beneficial effects of the diets, we will employ cross-species omics analysis. Once the candidates are identified, we will proceed with comprehensive genetic analysis of these molecules in worms to address their potential role in aging and metabolism. (AU) | |