Study of the involvement of impact in the effects of caloric restriction in C. elegans

• Grant number: 12/24490-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2013
• End date: March 31, 2015
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Rafael Ferraz Bannitz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In recent decades, obesity has come to become a major global public health problem, resulting in the increased prevalence of chronic diseases such as coronary heart disease, type 2 diabetes, cancer, among others. Likewise, the increase in the elderly population has contributed to the increased incidence of these and other chronic diseases. Data in the literature suggest that caloric restriction may be an effective intervention to combat the evils arising from obesity and aging, despite the practical limitations underlying prolonged food restriction. Therefore, it is important that nutritional or pharmacological alternatives are developed to mimic the effects of caloric restriction without its deleterious effects. Recently, it was demonstrated that the restriction of specific amino acids is sufficient to promote some acute effects of caloric restriction in mice, this being dependent on GCN2, a kinase activated by amino acid restriction that controls protein synthesis and stress responses. On the other hand, there is a protein called IMPACT that inhibits GCN2, thereby decreasing activation of this pathway and acting as a potential negative regulator of caloric restriction. Our group and other groups also showed that the miRNA processing pathway is essential for the effects of caloric restriction to take place, whereas overexpression of Dicer, an enzyme important in the synthesis of miRNAs, leads to an increase in life expectancy and stress resistance in the nematode C. elegans. Thus, we will use C. elegans as a model organism to characterize the effects of IMPACT protein on survival, the level of stress and energy stocks of animals subjected to ad libitum or caloric restriction diet. With this, we aim to contribute to the understanding of the mechanisms of action of caloric restriction, hoping to propose alternative interventions to prevent chronic diseases associated with obesity and aging. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, SILAS; SATO, VITOR N.; DE-SOUZA, EVANDRO A.; FERRAZ, RAFAEL C.; CAMARA, HENRIQUE; PINCA, ANA PAULA F.; MAZZOTTI, DIEGO R.; LOVCI, MICHAEL T.; TONON, GUILHERME; LOPES-RAMOS, CAMILA M.; et al. Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis. REDOX BIOLOGY, v. 18, p. 84-92, SEP 2018. (12/04064-0, 15/04264-8, 17/04377-2, 15/01316-7, 14/10814-8, 17/01184-9, 12/24490-4, 10/52557-0, 14/25270-3, 14/25068-0)

FERRAZ, RAFAEL C.; CAMARA, HENRIQUE; DE-SOUZA, EVANDRO A.; PINTO, SILAS; PINCA, ANA PAULA F.; SILVA, RICHARD C.; SATO, VITOR N.; CASTILHO, BEATRIZ A.; MORI, MARCELO A.. IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans. BMC Biology, v. 14, OCT 7 2016. (10/52557-0, 15/01316-7, 12/24490-4, 14/25270-3, 14/10814-8, 14/17145-4, 09/52047-5, 15/04264-8, 12/04064-0, 14/25068-0)