Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | DNA
During the aging process in mammals, tissue structure and physiological functions degrade. The cells also lose their ability to proliferate; entering senescence, and secreting inflammatory factors involved in the development of diseases related to aging, such as cancer and diabetes. Moreover, elimination of senescent cells induced in cancer patients treated with chemotherapy has been found to alleviate adverse side effects.
Several teams of the Frédéric-Joliot Life Sciences Institute at CEA are seeking to identify the senescent cells in situ, and characterize the mechanisms causing inflammation. The scientists have irradiated skin cells to induce DNA damage and trigger an aging process. They were able to identify an accumulation of histone H2A.J in senescent cells. The histones, proteins that DNA wraps around like a coil, participate in the regulation of gene expression. "We were the first team to observe H2A.J, and following this discovery, we constructed an antibody capable of specifically detecting this protein," said Carl Mann, researcher at the Frédéric-Joliot Life Sciences Institute. "Using this antibody, our German collaborators from the University of Saarland have shown that H2A.J is a good biomarker of senescent skin cells in mice and humans." In collaboration with the François-Jacob Institute of Biology at CEA, the researchers carried out what's called a transcriptomic analysis, a study on how genes are expressed. "It turns out that H2A.J promotes inflammatory gene expression in senescent cells," Mann said. "So its action may contribute to aging-associated chronic inflammation."
The next task consists of determining the mechanism of action of H2A.J. This work is currently in progress by the researchers and it may lead to the development of a drug to reduce the harmful chronic inflammation involved in aging-related diseases in humans.
Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression | Nature Communications
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.