DecAI: decoding aging initiative

• Grant number: 19/25958-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2020
• End date: April 30, 2024
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Agreement: Max Planck Society for the Advancement of Science
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Marcelo Alves da Silva Mori
• Principal researcher abroad: Adam Antebi
• Institution abroad: Max Planck Society, Dresden, Germany
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Claudia Regina Cavaglieri

Abstract

A number of pathways have been shown to regulate animal lifespan and organismal aging. The Antebi lab has recently discovered the nucleolus as a crucial focal point for these pathways. The nucleolus is a subnuclear organelle dedicated to rRNA production and ribogenesis, which also controls other key processes in the RNA metabolism of the cell, including small RNA processing and assembly of ribonucleoproteins. miRNAs are a class of small non-coding RNAs which regulate gene expression at the post-transcriptional level and have been implicated in development, disease, and aging. We and others have shown that miRNAs can influence lifespan, and that they can exert their effects in a cell-non-autonomous fashion. Our investigation of miRNA regulation in aging and cell-non-autonomy gave rise to the initiation of the DecAl cooperation in 2018, a project funded by CAPES and DAAD to allow human resource exchange. Early results from this collaboration have revealed that loss-of-function mutations in a miRNA/siRNA processing enzyme, DICER, affect nucleolar size, thereby potentially also placing the nucleolus as a link between small RNAs and aging. In addition, we found that incubation of human Jurkat cells with serum of exercised mice reduces nucleolus size and that this effect is dependent on the presence of DICER in adipocytes, suggesting that nucleolus size is cell non-autonomously controlled by adipose tissue small RNAs in response to exercise training. Despite the mounting evidence, the extent and mechanism of this regulation remains unclear. The focus of this proposal is therefore to (1) identify genes and circulating factors that affect miRNA and siRNA processing and RNA metabolism in aging, and (2) map the processes through which this regulation occurs, with a particular focus on the nucleolus. (AU)

Scientific publications

(5)

(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)

SCHIFFER, ISABELLE; GERISCH, BIRGIT; KAWAMURA, KAZUTO; LABOY, RAYMOND; HEWITT, JENNIFER; DENZEL, MARTIN SEBASTIAN; MORI, MARCELO A.; VANAPALLI, SIVA; SHEN, YIDONG; SYMMONS, ORSOLYA; et al. miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging. eLIFE, v. 10, JUL 27 2021. (19/25958-9)

TELLES, GUILHERME DEFANTE; CONCEICAO, MIGUEL SOARES; VECHIN, FELIPE CASSARO; LIBARDI, CLEITON AUGUSTO; MORI, MARCELO ALVES DA SILVA; DERCHAIN, SOPHIE; UGRINOWITSCH, CARLOS. Exercise-Induced Circulating microRNAs: Potential Key Factors in the Control of Breast Cancer. FRONTIERS IN PHYSIOLOGY, v. 13, p. 8-pg., 2022-06-16. (19/25958-9, 20/06032-5, 20/06262-0)

VERGANI-JUNIOR, CARLOS A.; TONON-DA-SILVA, GUILHERME; INAN, MEHMET DINCER; MORI, MARCELO A.. DICER: structure, function, and regulation. BIOPHYSICAL REVIEWS, v. 13, n. 6, p. 10-pg., 2021-12-01. (19/25958-9, 19/01587-1)

VERGANI-JUNIOR, CARLOS A.; MORO, RAISSA DE P.; PINTO, SILAS; DE-SOUZA, EVANDRO A.; CAMARA, HENRIQUE; BRAGA, DEISI L.; TONON-DA-SILVA, GUILHERME; KNITTEL, THIAGO L.; RUIZ, GABRIEL P.; LUDWIG, RAISSA G.; et al. An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress. NATURE COMMUNICATIONS, v. 15, n. 1, p. 15-pg., 2024-04-09. (17/01339-2, 19/25958-9, 21/08354-2, 17/01184-9, 14/50897-0, 19/04726-2, 22/05851-8, 17/23920-9, 19/01587-1, 23/08316-9, 14/10814-8, 18/11792-9, 18/21635-8, 16/15958-3, 17/04377-2)

CAMARA, HENRIQUE; INAN, MEHMET DINCER; VERGANI JR, CARLOS A.; PINTO, SILAS; KNITTEL, THIAGO L.; SALGUEIRO, WILLIAN G.; TONON-DA-SILVA, GUILHERME; RAMIREZ, JULIANA; DE MORAES, DIOGO; BRAGA, DEISI L.; et al. Tissue-specific overexpression of systemic RNA interference components limits lifespan in C. elegans. Gene, v. 895, p. 11-pg., 2023-11-25. (17/01339-2, 19/25958-9, 21/08354-2, 17/01184-9, 15/04264-8, 19/01587-1, 14/10814-8)