Study of Dicer effects on mitochondrial function, metabolism and aging in nematodes C. elegans

• Grant number: 14/25270-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2015
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Silas Pinto da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction, AP.JP

Abstract

In the last decade, aging of the world's population has called the attention of governmental agencies and research centers due to its great importance to society. However, it remains elusive what leads to aging and whether there are efficient ways of diminishing its deleterious effects. Therefore, advancements to better understanding the aging process are required in order to provide healthy aging and prevention of age-related diseases. Our previous data indicate that Dicer, an important RNAse III in the microRNA processing pathway, controls life span and stress resistance in C. elegans. Furthermore, we observed that reduction of Dicer expression by RNA interference (RNAi) decreases respiration in nematodes, which indicates mitochondrial changes. Moreover, worms carrying a null mutation in the Dicer gene do not exhibit mitochondria-related increase in life span promoted by metformin. According to these data, we propose a more detailed study of these mechanisms using C. elegans as model in order to assess whether the microRNA processing pathway is capable of regulating life span by controlling metabolic functions that are essential for growth and health. (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)