Group photo of participants at the SenesceX meeting at CNIO. Credit: Laura M. Lombardía / CNIO.
The SenesceX consortium investigates the role of cellular senescence in aging, cancer and embryo development.
American physician Leonard Hayflick discovered in 1961 that healthy human cells can only divide a certain number of times. When they reach that limit, they stop multiplying but do not die, instead they enter a stage called senescence. Since then, senescence has been associated with aging, although in recent years the paradigm has changed: senescence is now known to be involved in many vital processes.
Understanding the role of senescence in both the functioning of the healthy organism and in diseases, from developmental disorders to cancer, is now a very active area of research.
This week the SenesceX project meeting at the Spanish National Cancer Research Center (CNIO) brought together the senescence research community in Madrid and leaders in the field such as Masashi Narita, from Cancer Research UK Cambridge Institute, and Manuel Collado, from the Health Research Institute of Santiago de Compostela (IDIS) and president of the Spanish Society of Cellular Senescence.
SenesceX is a consortium funded by the Community of Madrid that “seeks to clarify the role of senescence in processes as diverse as embryonic development, aging and cancer, and to provide new therapeutic strategies to combat diseases resulting from inefficient senescence,” says Eva González Suárez, coordinator of SenesceX and head of the Transformation and Metastasis Group at the CNIO.
In relation to cancer, in particular, the evidence points to the fact that senescent cells promote tumor growth and aggressiveness. In addition, there are anti-tumor treatments (chemotherapy, radiation, CDK4/6 inhibitors) that induce senescence, and these senescent cells promote recurrences and metastasis.
Senescence involved in breast development
González Suárez, who researches breast cancer, has discovered that senescence is involved in the development of the mammary gland: “A few years ago we discovered that RANK, one of the proteins on which we focus part of the studies in my laboratory, induces senescence in mammary gland cells. This RANK-induced senescence has a dual role in cancer: on the one hand, it delays/protects from cancer, but it also contributes to tumors, once formed, being more aggressive”, explains González Suárez.
At the meeting at the CNIO, advances were presented on how the “deregulation” of senescence is responsible for the abnormalities of several genetic syndromes. The possible differences between dormant, senescent and persistent cells induced by anti-tumor treatments were also discussed, as well as the search for new anti-tumor therapies based on targeting senescent cells.
Also participating in SenesceX are Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group at the CNIO; Ignacio Palmero, from the Institute for Research in Biomedicine (IIB); Ana O’Loghen, from the Center for Biological Research (CIB); and Marta Magariños, from the Autonomous University of Madrid (UAM).