Effects of the Senolytic Association Quercetin and Dasatinib on the Inhibition of Pro-Inflammatory Cytokines and on Age-related Alveolar Bone Loss in Mice.

• Grant number: 22/16482-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: January 31, 2025
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Ana Lia Anbinder
• Grantee: Luisa Souza Battistelli
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. São José dos Campos , SP, Brazil

Abstract

Aging is associated to alveolar bone loss (ABL) and to an increase in periodontitis prevalence and severity. Besides oral hygiene, there are no therapeutic strategies to effectively prevent aging-related ABL. Cellular senescence is characterized by irreversible cell cycle arrest and a senescence-associated secretory phenotype, with production of cytokines which, if not efficiently cleared, are source of chronic inflammation. Senolytics induce senescent cells to apoptosis and their use have shown encouraging results in alleviating age-related systemic bone loss. An accumulation of senescent alveolar bone osteocytes was reported in aging mice, and these cells were shown to produce inflammatory cytokines in vitro, providing a pro-osteoclastogenic environment that could contribute to ABL in aging. Our hypothesis is that cell senescence is an integral part of the process whereby aging leads to ABL, and that senescent cell clearance can inhibit it. Mice will be preventive and chronically treated (10 months) with the senolytics combination Dasatinib and Quercetin as a strategy to induce osteocytes apoptosis and determine if their clearance can avoid age-related ABL. The alveolar bone loss and gene expression of Il1-², Il-6 e Tnf-± will be quantified using computerized microtomography and molecular biology. The data will be submitted to the most convenient statistical test.