Evaluation of the Senolytic Potential of Lithium Microdoses in an Astrocyte-Neuron Coculture Model

• Grant number: 26/08632-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2026
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Tânia Araújo Viel
• Grantee: Breno Nunes Santos
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/06017-7 - Aging-related neurodegenerative disorders: from the cell to the patient, AP.TEM

Abstract

Alzheimer's disease (AD) is the leading cause of dementia worldwide and still lacks therapies capable of modifying its course. Recent evidence indicates that cellular senescence and the accumulation of senescent cells in the central nervous system, particularly astrocytes, contribute to the persistence of chronic neuroinflammation and the progression of neurodegeneration. Senotherapeutic strategies have emerged as promising approaches in this context; however, the number of compounds with senolytic potential in the CNS remains limited. Lithium, a drug classically used in psychiatry and previously associated with neuroprotective effects at microdoses, has been shown to modulate phenotypes associated with cellular senescence, yet the mechanism of its potential senolytic effect remains unknown. This project will investigate the senolytic potential of microdoses of lithium carbonate on astrocytes exhibiting a amyloid-beta-induced senescent phenotype, employing a neuroglial coculture model that enables the assessment of cellular selectivity and neuronal impact. Complementary assays of cell viability, membrane integrity, cell senescence level, and apoptosis by flow cytometry will be performed. The study is expected to contribute to the understanding of lithium's effects on mechanisms associated with cellular aging and to the development of innovative therapeutic strategies for AD. (AU)