2023-09-26 23:00:00
As we know, age remains one of the main risk factors for the development of numerous pathologies such as viral or bacterial infections, neurodegenerative diseases but also cancers.
Nowadays, the notion of “ healthy aging » suggests that targeting aging rather than its consequences would probably be a much better idea for reducing morbidity in the elderly population.
In France, you should know that more than two thirds of new cancers occur in people aged over 65.
Their appearance with age is explained in particular by the accumulation of genetic alterations during life, less efficient DNA repair mechanisms, but also by an aging immune system with diminished protective functions; what we call in medical jargon: immunosenescence.
Over time, DNA becomes fragile with the development of genomic instability. However, when cells patrol the different tissues of the body, the cells of the immune system are sensitive to deformations which alter their nucleus and promote DNA breaks.
To maintain the structure of the nucleus and therefore genomic integrity, the cell relies on a dense network of proteins of which lamins are a part. Among them, lamin A/C is particularly studied because it undergoes alterations during aging.
In addition, mutations in the gene that codes for this protein are known to be the cause of early aging syndromes!
« Repeated disruptions of the nuclear envelope lead to DNA damage. It is essential to fully understand the processes involved at this level because they promote not only the aging of the body but also the development of cancers. » explains Dr Nicolas Manel, research director at Inserm and team leader at the Institut Curie.
And this specialist continues: “ for example, ruptures of the nucleus make the DNA “visible” by degradation proteins, then triggering a response from the cell which will promote the development of metastases ».
The Institut Curie therefore studied a new experimental model in which the cells of the immune system would be deficient in lamin A/C. The researchers looked at lung macrophages that are highly dependent on lamin A/C for survival.
Remember that these alveolar macrophages have the role of constantly monitoring the lungs and they constitute one of the main entry routes for many pathogens.
The researchers showed that in the absence of lamin A/C, alveolar macrophages showed severe signs of nuclear fractures and DNA damage, leading to a drastic reduction in their numbers in the lungs.
Furthermore, surviving alveolar macrophages exhibited many characteristics similar to aged alveolar macrophages and accumulated markers characteristic of aging.
This team of researchers also demonstrated that in the absence of lamin A/C in macrophages, the implantation and growth of lung tumors was much faster, favored by the dysfunction of aged macrophages.
The loss of lamin A/C would therefore represent a mechanism of aging of alveolar macrophages and a study model of choice to understand how lung cancers develop in the elderly.
« Our results open up numerous perspectives for the study of the aging of the immune system caused by the breakdown of the nuclear envelope and the reduction in its effectiveness against infections and tumors, in the lungs, but also in other organs. », concludes Dr Nicolas Manel.
This work is funded to the tune of 2.5 million euros as part of the “Cancer and Aging” call for projects from the ARC Foundation for cancer research.
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