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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis

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Author(s):
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Pinto, Silas [1, 2] ; Sato, Vitor N. [1] ; De-Souza, Evandro A. [1, 2] ; Ferraz, Rafael C. [1] ; Camara, Henrique [1, 2] ; Pinca, Ana Paula F. [1, 2] ; Mazzotti, Diego R. [3] ; Lovci, Michael T. [4] ; Tonon, Guilherme [2] ; Lopes-Ramos, Camila M. [5] ; Parmigiani, Raphael B. [5] ; Wurtele, Martin [6] ; Massirer, Katlin B. [4] ; Mori, Marcelo A. [1, 2]
Total Authors: 14
Affiliation:
[1] Fed Univ Sao Paulo UNIFESP, Sao Paulo Sch Med, Program Mol Biol, Dept Biophys, Sao Paulo, SP - Brazil
[2] Univ Campinas UNICAMP, Inst Biol, Program Genet & Mol Biol, Dept Biochem & Tissue Biol, Lab Aging Biol LaBE, Campinas, SP - Brazil
[3] Fed Univ Sao Paulo UNIFESP, Sao Paulo Sch Med, Dept Psychobiol, Sao Paulo, SP - Brazil
[4] Univ Campinas UNICAMP, Ctr Mol Biol & Genet Engn CBMEG, Campinas, SP - Brazil
[5] Hosp Sirio Libanes, Mol Oncol Ctr, Sao Paulo, SP - Brazil
[6] Fed Univ Sao Paulo UNIFESP, Inst Sci & Technol, Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: REDOX BIOLOGY; v. 18, p. 84-92, SEP 2018.
Web of Science Citations: 6
Abstract

Alterations in microRNA (miRNA) processing have been previously linked to aging. Here we used the small molecule enoxacin to pharmacologically interfere with miRNA biogenesis and study how it affects aging in C. elegans. Enoxacin extended worm lifespan and promoted survival under normal and oxidative stress conditions. Enoxacin-induced longevity required the transcription factor SKN-1/Nrf2 and was blunted by the antioxidant N-acetyl-cysteine, suggesting a prooxidant-mediated mitohormetic response. The longevity effects of enoxacin were also dependent on the miRNA pathway, consistent with changes in miRNA expression elicited by the drug. Among these differentially expressed miRNAs, the widely conserved miR-34-5p was found to play an important role in enoxacin-mediated longevity. Enoxacin treatment down-regulated miR-34-5p and did not further extend lifespan of long-lived mir-34 mutants. Moreover, N-acetyl-cysteine abrogated mir-34(gk437)-induced longevity. Evidence also points to double-stranded RNA-specific adenosine deaminases (ADARs) as new targets of enoxacin since ADAR loss-of-function abrogates enoxacin-induced lifespan extension. Thus, enoxacin increases lifespan by reducing miR-34-5p levels, interfering with the redox balance and promoting healthspan. (AU)

FAPESP's process: 15/04264-8 - Phenotypic screen of nematodes C. elegans mutants for proteins necessary to systemic RNAi
Grantee:Henrique Camara
Support type: Scholarships in Brazil - Master
FAPESP's process: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics
Grantee:Marcelo Alves da Silva Mori
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/25068-0 - Unraveling new mechanisms responsible for the cell non-autonomous control of proteostasis in c. elegans
Grantee:Ana Paula Forti Pinca
Support type: Scholarships in Brazil - Master
FAPESP's process: 15/01316-7 - Dicer, miRNAs and the control of mitochondrial function in the context of aging and caloric restriction
Grantee:Marcelo Alves da Silva Mori
Support type: Regular Research Grants
FAPESP's process: 17/04377-2 - Study of Dicer effects on mitochondrial function, metabolism and aging in c. elegans nematodes
Grantee:Silas Pinto da Silva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/25270-3 - Study of Dicer effects on mitochondrial function, metabolism and aging in nematodes C. elegans
Grantee:Silas Pinto da Silva
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/24490-4 - Study of the involvement of impact in the effects of caloric restriction in c. elegans
Grantee:Rafael Ferraz Bannitz
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/04064-0 - Search for a pharmacological intervention to mimic the beneficial effects of caloric restriction in c. elegans
Grantee:Vitor Neves Sato
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 14/10814-8 - Determination of factors that controls Dicer expression in vivo in C. elegans
Grantee:Evandro Araújo de Souza
Support type: Scholarships in Brazil - Master