Identification of stroke protection mechanisms using vascularized organoids from healthy centenarians

• Grant number: 23/05836-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Amanda Faria Assoni
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aging is a risk factor for most human chronic diseases, including cardiovascular disease, cancer, and neurodegenerative diseases. Currently, the healthy lifespan of individuals has not increased as much as life expectancy. Therefore, it is paramount to investigate factors underlying "healthy aging", which means maintaining functional capacity in old age by delaying the progression of age-related pathological conditions. According to the World Health Organization, Cerebrovascular Accident (CVA) is the leading cause of death and disability worldwide. In this context, centenarians who had no strokes throughout their lives, despite their advanced age and independent from daily routine habits, are intriguing and open up possibilities for exploring the genetic mechanisms involved in this resistance. Recent studies have focused on developing vascularized brain organoids to understand better the development and function of blood vessels in the brain. In this context, the proposed study aims to use single-cell analysis to compare organoids derived from healthy centenarians with those derived from individuals who died due to a stroke. By identifying critical differences at the single-cell level, we hope to recognize the primary cell types and mechanisms underlying aging and stroke susceptibility, potentially highlighting new therapeutic targets for disease prevention and treatment.