Exploration de la relation croisée entre la sénescence cellulaire, le cancer et le vieillissement

 

Francis Rodier

Centre de recherche du CHUM

 

Domaine : cancer

Programme chercheurs-boursiers - Junior 2

Concours 2016-2017

Why do we get more cancer as we get older and how to treat it: the role of aging cells

Just like us, individual mammalian cells get old. This cellular aging phenomenon, termed cellular senescence, is normally a good thing. Cellular aging is hardwired into a cell genetic program and is activated in response to cellular stresses or damages that could otherwise turn a normal cell into a cancer cell. Thus, cellular senescence prevents the apparition of cancer cells. But that's not the only reason why senescence exists, it is also activated by stress during tissue repair, mostly because senescent cells are adept at communicating with other cells and coordinate the repair process. Unfortunately, during normal aging or diseases associated with age, senescent cells accumulate beyond a normal threshold and disorganize tissues leading to organ dysfunctions including a paradoxical increase in tumor growth. What regulates this accumulation remains poorly understood, which provide opportunities for discovery and room for novel therapeutic interventions. My laboratory uses human, animal and cell models to understand how aging cells contribute to tissue malfunctions and we are attempting to use this knowledge to ameliorate human healthspan.

For example, one of our projects tries to understand how and why rheumatoid arthritis is associated with premature aging of the immune system. More recently, we have observed that cancer treatment also activate premature cellular aging, both in normal tissues and in the treated tumors. How premature cell senescence contributes to the outcome of cancer treatment remains unappreciated providing another discovery opportunity. Taking into account the good and bad sides of cellular aging (senescence), we are focusing our discovery efforts on determining which specific aspects are good or bad and whether we can optimize beneficial effects while negating detrimental effects to improve age- associated diseases or cancer treatments.