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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
Effective date (Start): September 01, 2017
Effective date (End): 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


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.

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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)
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, . (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)
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, . (14/50938-8, 09/16150-6, 17/04377-2)
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, . (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)
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, . (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, . (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, . (16/23008-5, 17/21628-9, 17/04377-2)

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