Tracking the life cycle of cells in senescence.

Cellular senescence is a biological program where cells permanently cease to divide in response to molecular damage, activating the senescence-associated secretory phenotype (SASP). SASP recruits the immune system to clear these cells. Senescence plays a crucial role in processes like development, wound healing, and cancer resistance, but its accumulation with age can be detrimental, contributing to systemic inflammation. Recent single-cell technology studies have revealed significant heterogeneity in the senescent phenotype. Most research has focused on the variation in cell types and different forms of senescence induction. However, a less explored aspect is the age of a senescent cell, considering both the cell’s age at the onset of senescence and the duration it remains in this state. Our previous work and preliminary results indicate that the senescence phenotype evolves from early to deeper states, with significant changes in the transcriptome, particularly the SASP, and the epigenome. This project aims to study how the senescence phenotype changes between young and old cells and as a function of time in senescence (Aim 1). Additionally, we will advance recent technology based on a multi-symbol molecular recorder to track the duration of cells in the senescent state (Aim 2). Ultimately, our project will lay the foundation for studying the age of senescent cells in vivo.