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Study of protective genetic variants in resilient nonagenarians and centenarians

Grant number: 20/09702-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2020
Effective date (End): October 31, 2022
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Cooperation agreement: CNPq - INCTs
Principal researcher:Mayana Zatz
Grantee:Mateus Vidigal de Castro
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/50931-3 - Aging and genetic disorders: genomics and metagenomics, AP.TEM

Abstract

One of the major challenges of modern science is to understand the genetic mechanisms behind the healthy aging process. Genome analysis of those who reached nine or more decades of life without any cognitive decline is a promising tool for investigating the genetic factors and variables involved in healthy longevity. In this sense, the objective of this study will be to identify genes involved in healthy aging and how these genes act for longevity, based on data from healthy elderly people over 90 years old, who led independent lives and did not develop frequent diseases at this age, such as Parkinson's or Alzheimer's (cognitively resilient) (Group 90+) - as opposed to adults under 60 who have acquired some cognitive decline (Group 60-). Also, we are currently experiencing a pandemic (COVID-19) caused by the new coronavirus (SARSCoV-2); in which elderly individuals are considered a risk group and, therefore, more susceptible. It is in this scenario that we will also investigate the resilience from an immunological point of view in these individuals, when comparing two extremes:elderly people over 90 years old with a history of infection by the referred virus, asymptomatic or cured (Group 90 + / COVID-19 +) and young people and adults under60 with a negative outcome (death) from Covid-19 (Group 60- / COVID-19 +). Individuals who will compose the groups are residents of São Paulo City and will be selected through the screening of cognitive status and diagnosis of COVID-19. Biological samples of these individuals will be used for genomic sequencing and functional evaluation from cell models such as neurons, muscle cells and endothelial cells - obtained from induced pluripotency stem cells (iPSC), which will be derived from erythroblasts. The identification of differences between "90+"s and "60-"s groups could validate and detect potential biomarkers involved with the healthy aging process and cognitive and immunological resilience. We believe that this study can make great contributions to better understanding of the genetic factors that determine healthy aging, longevity and resilience - filling an important gap in the knowledge of these biological processes and opens a new perspective in facing the current pandemic, with the potential to suggest new therapeutic targets.

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Scientific publications
(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)
CASTELLI, ERICK C.; DE CASTRO, V, MATEUS; NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; SILVA, NAYANE S. B.; ANDRADE, HELOISA S.; SOUZA, ANDREIA S.; PEREIRA, RAPHAELA N.; CASTRO, CAMILA F. B.; MENDES-JUNIOR, CELSO T.; MEYER, DIOGO; NUNES, KELLY; MATOS, LARISSA R. B.; SILVA, MONIZE V. R.; WANG, JAQUELINE Y. T.; ESPOSITO, JOYCE; CORIA, VIVIAN R.; BORTOLIN, RAUL H.; HIRATA, MARIO H.; MAGAWA, JHOSIENE Y.; CUNHA-NETO, EDECIO; COELHO, VERONICA; SANTOS, KEITY S.; MARIN, MARIA LUCIA C.; KALIL, JORGE; MITNE-NETO, MIGUEL; MACIEL, RUI M. B.; PASSOS-BUENO, MARIA RITA; ZATZ, MAYANA. MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals. FRONTIERS IN IMMUNOLOGY, v. 12, SEP 28 2021. Web of Science Citations: 0.
BASTARD, PAUL; GERVAIS, ADRIAN; LE VOYER, TOM; ROSAIN, JEREMIE; PHILIPPOT, QUENTIN; MANRY, JEREMY; MICHAILIDIS, ELEFTHERIOS; HOFFMANN, HANS-HEINRICH; ETO, SHOHEI; GARCIA-PRAT, MARINA; BIZIEN, LUCY; PARRA-MARTINEZ, ALBA; YANG, RUI; HALJASMAGI, LIIS; MIGAUD, MELANIE; SAREKANNU, KARITA; MASLOVSKAJA, JULIA; DE PROST, NICOLAS; TANDJAOUI-LAMBIOTTE, YACINE; LUYT, CHARLES-EDOUARD; AMADOR-BORRERO, BLANCA; GAUDET, ALEXANDRE; POISSY, JULIEN; MOREL, PASCAL; RICHARD, PASCALE; COGNASSE, FABRICE; TROYA, JESUS; TROUILLET-ASSANT, SOPHIE; BELOT, ALEXANDRE; SAKER, KAHINA; GARCON, PIERRE; RIVIERE, JACQUES G.; LAGIER, JEAN-CHRISTOPHE; GENTILE, STEPHANIE; ROSEN, LINDSEY B.; SHAW, ELANA; MORIO, TOMOHIRO; TANAKA, JUNKO; DALMAU, DAVID; THARAUX, PIERRE-LOUIS; SENE, DAMIEN; STEPANIAN, ALAIN; MEGARBANE, BRUNO; TRIANTAFYLLIA, VASILIKI; FEKKAR, ARNAUD; HEATH, JAMES R.; FRANCO, JOSE LUIS; ANAYA, JUAN-MANUEL; SOLE-VIOLAN, JORDI; IMBERTI, LUISA; BIONDI, ANDREA; BONFANTI, PAOLO; CASTAGNOLI, RICCARDO; DELMONTE, OTTAVIA M.; ZHANG, YU; SNOW, ANDREW L.; HOLLAND, STEVEN M.; BIGGS, CATHERINE M.; MONCADA-VELEZ, MARCELA; ARIAS, ANDRES AUGUSTO; LORENZO, LAZARO; BOUCHERIT, SORAYA; COULIBALY, BOUBACAR; ANGLICHEAU, DANY; PLANAS, ANNA M.; HAERYNCK, FILOMEEN; DUVLIS, SOTIRIJA; NUSSBAUM, ROBERT L.; OZCELIK, TAYFUN; KELES, SEVGI; BOUSFIHA, AHMED A.; EL BAKKOURI, JALILA; RAMIREZ-SANTANA, CAROLINA; PAUL, STEPHANE; PAN-HAMMARSTROM, QIANG; HAMMARSTROM, LENNART; DUPONT, ANNABELLE; KUROLAP, ALINA; METZ, CHRISTINE N.; AIUTI, ALESSANDRO; CASARI, GIORGIO; LAMPASONA, VITO; CICERI, FABIO; BARREIROS, LUCILA A.; DOMINGUEZ-GARRIDO, ELENA; VIDIGAL, MATEUS; ZATZ, MAYANA; VAN DE BEEK, DIEDERIK; SAHANIC, SABINA; TANCEVSKI, IVAN; STEPANOVSKYY, YURII; BOYARCHUK, OKSANA; NUKUI, YOKO; TSUMURA, MIYUKI; VIDAUR, LORETO; TANGYE, STUART G.; BURREL, SONIA; DUFFY, DARRAGH; QUINTANA-MURCI, LLUIS; KLOCPERK, ADAM; KANN, NELLI Y.; SHCHERBINA, ANNA; LAU, YU-LUNG; LEUNG, DANIEL; COULONGEAT, MATTHIEU; MARLET, JULIEN; KONING, RUTGER; REYES, LUIS FELIPE; CHAUVINEAU-GRENIER, ANGELIQUE; VENET, FABIENNE; MONNERET, GUILLAUME; NUSSENZWEIG, MICHEL C.; ARRESTIER, ROMAIN; BOUDHABHAY, IDRIS; BARIS-FELDMAN, HAGIT; HAGIN, DAVID; WAUTERS, JOOST; MEYTS, ISABELLE; DYER, ADAM H.; KENNELLY, SEAN P.; BOURKE, NOLLAIG M.; HALWANI, RABIH; SHARIF-ASKARI, NARJES SAHEB; DORGHAM, KARIM; SALLETTE, JEROME; SEDKAOUI, SOUAD MEHLAL; ALKHATER, SUZAN; RIGO-BONNIN, RAUL; MORANDEIRA, FRANCISCO; ROUSSEL, LUCIE; VINH, DONALD C.; OSTROWSKI, SISSE RYE; CONDINO-NETO, ANTONIO; PRANDO, CAROLINA; BONDARENKO, ANASTASIIA; SPAAN, ANDRAS N.; GILARDIN, LAURENT; FELLAY, JACQUES; LYONNET, STANISLAS; BILGUVAR, KAYA; LIFTON, RICHARD P.; MANE, SHRIKANT; ANDERSON, MARK S.; BOISSON, BERTRAND; BEZIAT, VIVIEN; ZHANG, SHEN-YING; ANDREAKOS, EVANGELOS; HERMINE, OLIVIER; PUJOL, AURORA; PETERSON, PART; MOGENSEN, TRINE H.; ROWEN, LEE; MOND, JAMES; DEBETTE, STEPHANIE; DE LAMBALLERIE, XAVIER; DUVAL, XAVIER; MENTRE, FRANCE; ZINS, MARIE; SOLER-PALACIN, PERE; COLOBRAN, ROGER; GOROCHOV, GUY; SOLANICH, XAVIER; SUSEN, SOPHIE; MARTINEZ-PICADO, JAVIER; RAOULT, DIDIER; VASSE, MARC; GREGERSEN, PETER K.; PIEMONTI, LORENZO; RODRIGUEZ-GALLEGO, CARLOS; NOTARANGELO, LUIGI D.; SU, HELEN C.; KISAND, KAI; OKADA, SATOSHI; PUEL, ANNE; JOUANGUY, EMMANUELLE; RICE, CHARLES M.; TIBERGHIEN, PIERRE; ZHANG, QIAN; COBAT, AURELIE; ABEL, LAURENT; CASANOVA, JEAN-LAURENT; LAB, HGID; CLINICIANS, COVID; CLINICIANS, COVID-STORM; GRP, NIAID IMMUNE RESPONSE COVID; GRP, NH-COVAIR STUDY; CHGE, DANISH; STUDY, DANISH BLOOD DONOR; INTEREST, ST JAMESS HOSP SARS COV2; GRP, FRENCH COVID COHORT STUDY; COVID-GRP, IMAGINE; CONSORTIUM, MILIEU INTERIEUR; COHORT, COV-CONTACT; INV, AMSTERDAM UMC COVID-19 BIOBANK; EFFT, COVID HUMAN GENETIC; COHORT, CONSTANCES; STUDY, 3C-DIJON; HEALTHCARE, CERBA; GRP, ETAB SANG STUDY. Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected individuals over 70 years old and account for similar to 20% of COVID-19 deaths. SCIENCE IMMUNOLOGY, v. 6, n. 62 AUG 2021. Web of Science Citations: 7.

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