Grant: Travel Awards - Institute Community Support

Cells divide for several reasons, including growth, repairing damage, and replacing old cells. Cells have end caps called telomeres that protect their DNA during divisions. Every time a cell divides, the telomeres shorten. Once these telomeres become too short, the cell experiences stress, transitioning it into a state where it is unable to grow, called senescence. This process occurs during aging, and the accumulation of these cells increases the risk of disorders like dementia and atherosclerosis. The continuous stress from these shortened telomeres activates the p53 protein, whose role is to protect the body from tumour formation by inducing death, arrest, or senescence. The p53 protein gets activated from chemical changes called phosphorylations and the timing of these changes are unknown. This represents a knowledge gap because defining how p53 activates could assist the understanding of the general aging process. Our earlier findings indicate that senescence may occur in two phases, with significance at 24 hours of p53 activation, where senescence becomes irreversible. Our laboratory also revealed that after two weeks of senescence, there is an activation of genes not traditionally linked to senescence initiation, further suggesting two-stages of senescence. Therefore, our experiments aim to map the times of p53 phosphorylation events and examine the expression of genes following senescence induction. To address this aim, a cell system will be developed to allow p53 to be activated based on temperature. After activating p53 at different times, and therefore inducing senescence, we will observe its and its target genes' activation. Since p53 is a key protector against stress, understanding its phosphorylation events and their consequences can improve the broad health of the population. It can assist in the general understanding of aging and assist in the development of therapeutics against premature aging syndromes, age-related diseases, and cancer.