At the end of his life, after havingdivided fifty or more times, ourcells often rest and “retire”. They enter a state known assenescenciain which they are still active but cannot duplicate any more, and which is associated with aging and also with cancer prevention. Now, research in which the Center for Genomic Regulation (CRG) has participated reveals a new detail: by secreting a cocktail of factors, senescent cells cantransmit your “retirement” status to other nearby cells.
The research, published this week in the journalNature Cell Biologyand directed by Jesús Gil, from the CRG, confirms something that has been suspected for a long time, but has never been proven: that cells can transmit the senescent state to their neighbors. “We have known for more than 20 years that senescent cells secrete a large number of factors, but it was not until about a decade ago that we realized that this was not a useless by-product or a curiosity, but could profoundly influence cells. of the surroundings “, Gil comments.
The effects of this set of secretions, known assenescence-associated secretory phenotype (SASP)They are not simple at all. “Depending on the cells and the environment, the senescent phenotype can promote or suppress the development of tumors,” says Gil.
What Gil and his team wondered about this ‘secretome’ or set of secretions, was whether it could cause senescence in other nearby cells. The answer was a resounding yes. “We have found that both in vitro [experimental laboratory cultures] and in vivo [real tissue], senescent cells are surrounded by normal cells that have adopted the senescent phenotype.” With the existence of this‘paracrine aging’Confirmed, the next step was to use quantitative proteomics in conjunction with drug screening to identify that multiple secreted factors were causing the transmission of senescence.
“We have identified factors produced by senescent cells that are responsible for enhancing the spread. These factors are mostly easy and soluble targets for drugs. That means that we can inhibit or activate them using drugs that are already available,” explains Gil. Defining what causes this secretome to increase or suppress tumor development will be crucial for thedevelopment of drugs that fight cancer.
