CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics

• Grant number: 17/01184-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2017
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Innovation Fund Denmark
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Marcelo Alves da Silva Mori
• Principal researcher abroad: Jonas Thue Treebak
• Institution abroad: University of Copenhagen, Copenhagen, Denmark
• Principal researcher abroad: Markus Herrgard
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Maria Cristina Foss de Freitas ; Niels Jessen
• Associated research grant(s): 20/04919-2 - Determining molecular candidates that contribute to the higher risk of COVID-19 in aged individuals, AP.R; 17/25583-0 - Multi-user equipment approved in grant 2017/01184-9: CFX384 touch real-time PCR detection system, AP.EMU; 17/17556-2 - Straightening collaboration between academia and industry to explore new molecules and targets to treat metabolic diseases, AV.EXT
• Associated scholarship(s): 19/21852-1 - Contribution of adipose tissue miRNAs in cardiac function, metabolism and remodeling, BP.PD; 19/04726-2 - Investigation of new tissue-specific mechanisms of aging control by caloric restriction in C. elegans, BP.DR; 19/08038-3 - Assessment of exosome circadian rhythmicity in mice, BP.MS; + associated scholarships 19/01587-1 - Study of the role of ALG-1 and its regulatory mechanisms in healthspan of Caenorhabditis elegans, BP.DD; 19/07575-5 - Role of Dicer in beige adipocyte differentiation and the influence of macrophages in this process, BP.IC; 18/21635-8 - Study of the role of miR-203-3p in adipose tissue metabolism and in the pathogenesis of metabolic diseases in mice, BP.DD; 18/11672-3 - Characterization in mice of novel genes involved in the evolutionarily conserved mechanisms of dietary restriction and its mimetics, BP.PD; 18/07703-0 - Uncovering new regulators of DAF-16/FOXO expression, BP.MS; 18/11792-9 - Characterization in C. elegans of novel genes involved in aging and the evolutionarily conserved mechanisms of dietary restriction mimetics, BP.DD; 17/23920-9 - Varredura e caracterização de moléculas circulantes que afetam o gasto energético, BP.DR; 18/02171-0 - Evaluation of the diurnal expression pattern of Dicer enzyme and its influence on the expression of clock genes in adipocytes, BP.IC; 17/22057-5 - Physiological effects and transgenerational inheritance induced by cholesterol-rich diet in Caenorhabditis elegans, BP.MS; 16/17075-1 - Daily Rhythm Changes in Dicer Expression in Adipose Tissue and the Impact over Metabolism, BP.PD - associated scholarships

Abstract

The overarching aim of this proposal is to delineate the common molecular networks in adipose tissue involved in the lifespan and health promoting effects of dietary restriction and its mimetics such as dietary Methionine Restriction (MR) and dietary supplementation with Nicotinamide Riboside (NR) - a dairy constituent that maintains NAD metabolism. To achieve that, we designed a pipeline to sort out biologically relevant pathways affected by these interventions. Briefly, we will perform omics of samples obtained from C. elegans, and adipose tissue and serum of mice and humans (healthy and/or type 2 diabetic) subjected to DR or its mimetic interventions. We will correlate these findings with lifespan and/or metabolic profiling and use bioinformatics tools to identify evolutionary conserved pathways that are commonly affected by the dietary interventions. The relevant pathways will then be scrutinized using gain- or loss-of-function models in C. elegans, mice and mammalian preadipocyte cell lines, providing new insights into how these dietary interventions affect health span in multiple organisms, including humans. (AU)

Scientific publications

(31)

(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)

LUDWIG, RAISSA G.; ROCHA, ANDREA L.; MORI, MARCELO A.. Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity. Cell Biology International, v. 42, n. 6, SI, p. 701-710, JUN 2018. (16/12294-7, 15/01316-7, 17/01184-9, 17/07975-8, 15/20822-0)

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)

LUDWIG, RAISSA G.; ROCHA, ANDREA L.; MORI, MARCELO A.. Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity. Cell Biology International, v. 42, n. 6, p. 10-pg., 2018-06-01. (17/01184-9, 17/07975-8, 15/20822-0, 16/12294-7, 15/01316-7)

ZONARI, ALESSANDRA; BRACE, LEAR E. E.; AL-KATIB, KALLIE; PORTO, WILLIAM F. F.; FOYT, DANIEL; GUIANG, MYLIENETH; CRUZ, EDGAR ANDRES OCHOA; MARSHALL, BAILEY; GENTZ, MELISSA; GUIMARAES, GABRIELA RAPOZO; et al. Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models. NPJ AGING, v. 9, n. 1, p. 15-pg., 2023-05-22. (17/22057-5, 17/01184-9)

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)

GUERRA, BEATRIZ A.; BRANDAO, BRUNA B.; PINTO, SILAS S.; SALGUEIRO, WILLIAN G.; DE-SOUZA, EVANDRO A.; REIS, FELIPE C. G.; BATISTA, THIAGO M.; CAVALCANTE-SILVA, VANESSA; D'ALMEIDA, VANIA; CASTILHO, BEATRIZ A.; et al. Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects. MOLECULAR METABOLISM, v. 29, p. 124-135, NOV 2019. (15/03292-8, 17/22057-5, 10/52557-0, 16/02207-0, 17/01184-9, 15/01316-7, 15/19530-5, 12/07259-7, 17/07975-8)

SALES, VICENCIA M.; GONCALVES-ZILLO, THAIS; CASTOLDI, ANGELA; BURGOS, MARINA; BRANQUINHO, JESSICA; BATISTA, CAROLINA; OLIVEIRA, VALERIA; SILVA, ELTON; CASTRO, CHARLLES H. M.; CAMARA, NIELS; et al. Kinin B-1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner. Diabetes, v. 68, n. 8, p. 1614-1623, AUG 2019. (17/07975-8, 17/01184-9, 14/27198-8)

BRAGA, DEISI L.; MOUSOVICH-NETO, FELIPPE; TONON-DA-SILVA, GUILHERME; SALGUEIRO, WILLIAN G.; MORI, MARCELO A.. Epigenetic changes during ageing and their underlying mechanisms. BIOGERONTOLOGY, v. 21, n. 4, p. 21-pg., 2020-04-30. (19/14391-8, 17/22057-5, 17/08829-5, 18/11672-3, 17/01184-9, 18/11792-9)

PELUSO, A. AUGUSTO; LUNDGAARD, AGNETE T.; BABAEI, PARIZAD; MOUSOVICH-NETO, FELIPPE; ROCHA, ANDREA L.; DAMGAARD, MADS V.; BAK, EMILIE G.; GNANASEKARAN, THIYAGARAJAN; DOLLERUP, OLE L.; TRAMMELL, SAMUEL A. J.; et al. Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans. NPJ AGING, v. 9, n. 1, p. 21-pg., 2023-04-03. (16/12294-7, 17/01184-9, 18/11672-3)

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)

RUIZ, GABRIEL PALERMO; CAMARA, HENRIQUE; FAZOLINI, NARAYANA P. B.; MORI, MARCELO A.. Extracellular miRNAs in redox signaling: Health, disease and potential therapies. Free Radical Biology and Medicine, v. 173, p. 170-187, SEP 2021. (17/01339-2, 17/01184-9, 18/21635-8, 17/23920-9, 17/07975-8)

BRAGA, DEISI L.; MOUSOVICH-NETO, FELIPPE; TONON-DA-SILVA, GUILHERME; SALGUEIRO, WILLIAN G.; MORI, MARCELO A.. Epigenetic changes during ageing and their underlying mechanisms. BIOGERONTOLOGY, v. 21, n. 4, SI, APR 2020. (18/11672-3, 17/22057-5, 18/11792-9, 17/08829-5, 19/14391-8, 17/01184-9)

SALGUEIRO, WILLIAN GOULART; SOARES, MARCELL VALANDRO; MARTINS, CASSIANO FIAD; PAULA, FAVERO REISDORFER; RIOS-ANJOS, RAFAELA MARIA; CARRAZONI, THIAGO; MORI, MARCELO A.; MUELLER, ROMAN-ULRICH; ASCHNER, MICHAEL; BELO, CHARISTON ANDRE DAL; et al. Dopaminergic modulation by quercetin: In silico and in vivo evidence using Caenorhabditis elegans as a model. Chemico-Biological Interactions, v. 382, p. 13-pg., 2023-09-01. (17/22057-5, 17/01184-9)

ROCHA, ANDREA LIVIA; GUERRA, BEATRIZ ALVES; BOUCHER, JEREMIE; MORI, MARCELO A.. A Method to Induce Brown/Beige Adipocyte Differentiation from Murine Preadipocytes. BIO-PROTOCOL, v. 11, n. 24, DEC 20 2021. (15/03292-8, 16/12294-7, 17/01184-9, 12/07259-7)

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)

MARCELO A. MORI. Aging: a New Perspective on an Old Issue. Anais da Academia Brasileira de Ciências, v. 92, n. 2, 2020-07-06. (17/01184-9, 17/25583-0)

MORI, MARCELO A.; LUDWIG, RAISSA G.; GARCIA-MARTIN, RUBEN; BRANDAO, BRUNA B.; KAHN, C. RONALD. Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease. Cell Metabolism, v. 30, n. 4, p. 656-673, OCT 1 2019. (17/23920-9, 17/07975-8, 17/01184-9)

TOWNSEND, LOGAN K.; BRUNETTA, HENVER S.; MORI, MARCELO A. S.. Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 319, n. 6, p. E1053-E1060, DEC 2020. (17/01184-9, 19/21852-1)

BRUNETTI, NATALIA S.; DAVANZO, GUSTAVO G.; DE MORAES, DIOGO; FERRARI, ALLAN J. R.; SOUZA, GABRIELA F.; MURARO, STEFANIE PRIMON; KNITTEL, THIAGO L.; BOLDRINI, VINICIUS O.; MONTEIRO, LAUAR B.; VIRGILIO-DA-SILVA, JOO VICTOR; et al. SARS-CoV-2 uses CD4 to infect T helper lymphocytes. eLIFE, v. 12, p. 26-pg., 2023-07-31. (20/04558-0, 15/15626-8, 19/06459-1, 19/04726-2, 19/16116-4, 19/05155-9, 19/13552-8, 16/18031-8, 19/00098-7, 20/04583-4, 16/00194-8, 21/08354-2, 19/17007-4, 19/22398-2, 17/01184-9, 19/14465-1, 20/04579-7, 13/08293-7, 18/14933-2, 17/23920-9, 19/06372-3, 16/24163-4, 16/23328-0, 20/04919-2, 20/04746-0)

SACCON, TATIANA DANDOLINI; MOUSOVICH-NETO, FELIPPE; LUDWIG, RAISSA GUIMARAES; CARREGARI, VICTOR CORASOLLA; DOS ANJOS SOUZA, ANA BEATRIZ; DOS PASSOS, AMANDA STEPHANE CRUZ; MARTINI, MATHEUS CAVALHEIRO; BARBOSA, PRISCILLA PASCHOAL; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. NATURE COMMUNICATIONS, v. 13, n. 1, p. 15-pg., 2022-09-29. (20/08716-9, 20/04558-0, 19/05155-9, 21/10373-5, 13/07607-8, 20/04919-2, 20/04746-0, 17/01184-9, 17/23920-9, 16/24163-4, 16/00194-8, 18/21635-8, 19/00098-7, 20/05040-4, 17/08264-8, 20/04579-7, 19/26119-0, 19/04726-2, 20/04583-4, 20/15959-5)

ROCHA, ANDREA LIVIA; DE LIMA, TANES IMAMURA; DE SOUZA, GERSON PROFETA; CORREA, RENAN OLIVEIRA; FERRUCCI, DANILO LOPES; RODRIGUES, BRUNO; LOPES-RAMOS, CAMILA; NILSSON, DANIEL; KNITTEL, THIAGO LEITE; CASTRO, POLLYANA RIBEIRO; et al. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. SCIENCE ADVANCES, v. 6, n. 49, DEC 2020. (10/52557-0, 17/01184-9, 18/15313-8, 16/23142-3, 17/07975-8, 16/24163-4, 15/01316-7, 16/12294-7)

DE MORAES, DIOGO; BUQUETE PAIVA, BRUNNO VIVONE; CURY, SARAH SANTILONI; ARAUJO JUNIOR, JOAO PESSOA; DA SILVA MORI, MARCELO ALVES; CARVALHO, ROBSON FRANCISCO; LUDWIG, RAISSA GUIMARAES. Prediction of SARS-CoV Interaction with Host Proteins during Lung Aging Reveals a Potential Role for TRIB3 in COVID-19. Aging and disease, v. 12, n. 1, p. 42-49, FEB 1 2021. (17/01184-9)

DE MORAES, DIOGO; MOUSOVICH-NETO, FELIPPE; CURY, SARAH SANTILONI; OLIVEIRA, JAKELINE; SOUZA, JEFERSON DOS SANTOS; FREIRE, PAULA PACCIELLI; DAL-PAI-SILVA, MAELI; MORI, MARCELO ALVES DA SILVA; FERNANDEZ, GEYSSON JAVIER; CARVALHO, ROBSON FRANCISCO. The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males. BIOMEDICINES, v. 11, n. 5, p. 14-pg., 2023-05-14. (17/01184-9)

FERRAZ-BANNITZ, RAFAEL; BERALDO, REBECA A.; PELUSO, A. AUGUSTO; DALL, MORTEN; BABAEI, PARIZAD; FOGLIETTI, RAYANA CARDOSO; MARTINS, LARISSA MARFORI; GOMES, PATRICIA MOREIRA; MARCHINI, JULIO SERGIO; SUEN, VIVIAN MARQUES MIGUEL; et al. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. NUTRIENTS, v. 14, n. 13, p. 18-pg., 2022-07-01. (15/12133-0, 17/01184-9)

TAN, DAN; KONDURI, SRIHARI; ERTUNC, MERIC ERIKCI; ZHANG, PAN; WANG, JUSTIN; CHANG, TINA; PINTO, ANTONIO F. M.; ROCHA, ANDREA; DONALDSON, CYNTHIA J.; VAUGHAN, JOAN M.; et al. A class of anti-inflammatory lipids decrease with aging in the central nervous system. Nature Chemical Biology, v. N/A, p. 28-pg., 2022-10-20. (17/01184-9)

CODO, ANA CAMPOS; DAVANZO, GUSTAVO GASTAO; MONTEIRO, LAUAR DE BRITO; DE SOUZA, GABRIELA FABIANO; MURARO, STEFANIE PRIMON; VIRGILIO-DA-SILVA, JOAO VICTOR; PRODONOFF, JULIANA SILVEIRA; CARREGARI, VICTOR CORASOLLA; OLIVEIRA DE BIAGI JUNIOR, CARLOS ALBERTO; CRUNFLI, FERNANDA; et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1 alpha/Glycolysis-Dependent Axis. Cell Metabolism, v. 32, n. 3, p. 15-pg., 2020-09-01. (19/00098-7, 20/04558-0, 20/04522-5, 19/06372-3, 16/18031-8, 15/15626-8, 16/23328-0, 17/01184-9, 20/04919-2, 20/04583-4, 20/04579-7, 18/22505-0, 20/04746-0)

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)

SANTORO, ADRIANA LEANDRA; VENDRAMINI, PEDRO H.; BRAGA, DEISI L.; MARTINS, LUCAS GELAIN; DOS SANTOS, GABRIEL F.; LIMA, GESIANE S.; TASIC, LJUBICA; MORI, MARCELO A.. Caenorhabditis elegans (C. elegans) sample preparation for metabolomics and lipidomics analysis - A review. TRAC-TRENDS IN ANALYTICAL CHEMISTRY, v. 169, p. 11-pg., 2023-10-25. (13/07607-8, 21/08354-2, 17/01184-9, 20/06057-8, 18/11792-9)

MORI, MARCELO A.. Editorial: Non-Coding RNAs: Entwining Metabolism and Aging. FRONTIERS IN ENDOCRINOLOGY, v. 9, p. 2-pg., 2018-03-19. (17/07975-8, 17/01184-9)

FERREIRA, JULIO C. B.; MORI, MARCELO A.; GROSS, ERIC R.. Mitochondrial Bioenergetics and Quality Control Mechanisms in Health and Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2019, p. 3-pg., 2019-01-20. (15/20783-5, 17/07975-8, 17/01184-9, 12/05765-2, 18/18627-3, 17/16694-2)