Study of protective genetic variants in resilient nonagenarians and centenarians

• Grant number: 20/09702-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2020
• End date: October 31, 2024
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Agreement: CNPq - INCTs
• Principal Investigator: Mayana Zatz
• Grantee: Mateus Vidigal de Castro
• Host 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 under 60 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. (AU)

Scientific publications

(7)

(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)

SHELTON, G. DIANE; MINOR, KATIE M.; VIEIRA, NATASSIA M.; KUNKEL, LOUIS M.; FRIEDENBERG, STEVEN G.; CULLEN, JONAH N.; GUO, LING T.; ZATZ, MAYANA; MICKELSON, JAMES R.. Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype. Neuromuscular Disorders, v. 32, n. 10, p. 6-pg., 2022-10-27. (13/08028-1, 14/50931-3, 20/09702-1)

CASTELLI, ERICK C.; DE CASTRO, MATEUS V.; NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; SILVA, NAYANE S. B.; PEREIRA, RAPHAELA N.; CIRIACO, VIVIANE A. O.; CASTRO, CAMILA F. B.; MENDES-JUNIOR, CELSO T.; SILVEIRA, ETIELE DE S.; et al. MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil. FRONTIERS IN IMMUNOLOGY, v. 13, p. 15-pg., 2022-10-25. (14/50931-3, 20/09702-1, 17/19223-0, 19/19998-8, 13/08028-1)

DE CASTRO, MATEUS V.; SILVA, MONIZE V. R.; OLIVEIRA, LUANA DE M.; GOZZI-SILVA, SARAH C.; NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; MAGALHAES, MONIZE L.; DA ROCHA, KATIA M.; NUNES, KELLY; CASTELLI, ERICK C.; et al. Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, v. 129, p. 9-pg., 2023-02-27. (13/08028-1, 14/50931-3, 20/09702-1)

ZATZ, MAYANA; SILVA, MONIZE V. R.; DE CASTRO, MATEUS, V; NASLAVSKY, MICHEL S.. The 90 plus: longevity and COVID-19 survival. MOLECULAR PSYCHIATRY, v. 27, n. 4, p. 9-pg., 2022-02-08. (20/09702-1, 13/08028-1, 14/50931-3)

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.; et al. MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals. FRONTIERS IN IMMUNOLOGY, v. 12, SEP 28 2021. (13/08028-1, 19/19998-8, 20/09702-1, 17/19223-0, 14/50931-3)

BASTARD, PAUL; GERVAIS, ADRIAN; LE VOYER, TOM; ROSAIN, JEREMIE; PHILIPPOT, QUENTIN; MANRY, JEREMY; MICHAILIDIS, ELEFTHERIOS; HOFFMANN, HANS-HEINRICH; ETO, SHOHEI; GARCIA-PRAT, MARINA; et al. 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. (20/09702-1)

DE CASTRO, MATEUS, V; SILVA, MONIZE V. R.; SOARES, FLAVIA B.; CORIA, VIVIAN R.; NASLAVSKY, MICHEL S.; SCLIAR, MARILIA O.; CASTELLI, ERICK C.; DE OLIVEIRA, JAMILE R.; SASAHARA, GREYCE L.; SANTOS, KEITY S.; et al. Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: A case report. FRONTIERS IN MEDICINE, v. 9, p. 8-pg., 2022-09-29. (20/09702-1, 13/08028-1, 14/50890-5)