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

• Grant number: 17/04377-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2017
• End date: March 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Silas Pinto da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Aging is one of the most significant trends of the 21st century and has worried governments around the world for its involvement in some sectors of society. Understanding how life time is controlled is necessary to propose strategies ensuring healthy aging for the population. There are many pathways involved in the control of life time of the organisms in multiple species, and between then, miRNA processing pathway seems to be extremely im-portant. Obtained in the first part of this project, our data suggest that Dicer silencing, a key enzyme in the miR-NAs and other small RNAs processing, is deleterious in C. elegans leading to a decrease in the life span of wild-type worms and slowing their development. In addition, this intervention promotes the reduction of respiration, causes oxidative stress and inhibits the beneficial effects of mutations or interventions that depend on mitochon-drial function to extend the life span. Data published by our group using mice as a model corroborates our findings and strengthen the hypothesis that Dicer is fundamental for the metabolism and determination of the life time in several species. However, the mechanisms for which the effects are given are still unknown. We propose, there-fore, a complementary study to better understand these mechanisms in attempt to find solutions that promote a healthier aging.

Scientific publications

(6)

(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)

DE-SOUZA, EVANDRO A.; CAMARA, HENRIQUE; SALGUEIRO, WILLIAN G.; MORO, RAISSA P.; KNITTEL, THIAGO L.; TONON, GUILHERME; PINTO, SILAS; PINCA, ANA PAULA F.; ANTEBI, ADAM; PASQUINELLI, AMY E.; et al. RNA interference may result in unexpected phenotypes in Caenorhabditis elegans. Nucleic Acids Research, v. 47, n. 8, p. 3957-3969, MAY 7 2019. (12/00195-3, 10/52557-0, 17/22057-5, 17/04377-2, 17/03423-0, 16/02207-0, 17/08829-5, 15/01316-7, 17/01339-2, 14/10814-8, 17/01184-9, 14/25068-0, 16/15958-3)

FERRUCCI, DANILO; SILVA, SILAS PINTO; ROCHA, ANDR; NASCIMENTO, LUCAS; VIEIRA, ANDRE SCHWAMBACH; TABOGA, SEBASTIAO ROBERTO; MORI, MARCELO; LENZ-CESAR, CARLOS; CARVALHO, HERNANDES F.. Dietary fatty acid quality affects systemic parameters and promotes prostatitis and pre-neoplastic lesions. SCIENTIFIC REPORTS, v. 9, DEC 17 2019. (14/50938-8, 09/16150-6, 17/04377-2)

BRANDAO, BRUNA B.; MADSEN, SOREN; RABIEE, ATEFEH; OLIVERIO, MATTEO; RUIZ, GABRIEL P.; FERRUCCI, DANILO L.; BRANQUINHO, JESSICA L.; RAZOLLI, DANIELA; PINTO, SILAS; NIELSEN, THOMAS S.; et al. Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 38, p. 23932-23941, SEP 22 2020. (17/03423-0, 15/01316-7, 17/04377-2, 12/06238-6, 15/03292-8, 17/01184-9, 12/04079-8, 18/21635-8, 17/07975-8)

DE-SOUZA, EVANDRO A.; PIMENTEL, FELIPE S. A.; DE-QUEIROZ, ANA LUIZA F. V.; CAMARA, HENRIQUE; FELIX-FORMIGA, MIKAELLA L.; MACHADO, CAIO M.; PINTO, SILAS; GALINA, ANTONIO; MORI, MARCELO A.; MONTERO-LOMELI, MONICA; et al. The yeast protein Ubx4p contributes to mitochondrial respiration and lithium?galactose?mediated activation of the unfolded protein response. Journal of Biological Chemistry, v. 295, n. 12, p. 3773-3782, MAR 20 2020. (17/01184-9, 17/01339-2, 17/04377-2)

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)

LIMA, TANES I.; GUIMARAES, DIMITRIUS SANTIAGO P. S. F.; OLIVEIRA, ANDRE G.; ARAUJO, HYGOR; SPONTON, CARLOS H. G.; SOUZA-PINTO, NADJA C.; SAITO, ANGELA; FIGUEIRA, ANA CAROLINA M.; PALAMETA, SOLEDAD; BAJGELMAN, MARCIO CHAIM; et al. Opposing action of NCoR1 and PGC-1 alpha in mitochondrial redox homeostasis. Free Radical Biology and Medicine, v. 143, p. 203-208, NOV 1 2019. (16/23008-5, 17/21628-9, 17/04377-2)