Functional and molecular characterization of the brain in Brazilian super-agers: new perspectives in the understanding of healthy neuro aging

• Grant number: 22/14961-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2023
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Moníze Valéria Ramos da Silva
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Human society is going through a major demographic Human society is going through a major demographic transition: decreasing birth rates and increasing life expectancy. In other words, we live in an increasingly aged world. Within this inevitable perspective, an increase in the prevalence of aging-related diseases has been observed, among them the cognitive deficits as for example in Alzheimer's disease (AD), one of the main causes of death today. On the other hand, cases of cognitively healthy centenarians despite their advanced age are intriguing and open possibilities for exploring the possible genetic mechanisms involved in this cognitive resilience. Elucidating such mechanisms would allow the long-term search for the "Grail of cognition", assisting in the development of diagnostic methods as well as new therapies capable of preventing the loss of cognition. This study aims to elucidate such protective mechanisms in admixed Brazilian centenarians using single-nucleus sequencing (single-nuclei RNA seq). Therefore, cortical brain organoids will be derived from induced pluripotent stem cells from cognitively resilient centenarians and centenarians with cognitive decline by presumed AD diagnosis and characterized at the molecular level. This is the junction of advanced sequencing and cell culture techniques for the understanding of healthy neuro-aging in Brazil. (AU)