2023-09-23 06:00:01
Cancer and aging are closely linked processes and yet the mechanisms at the heart of this relationship remain relatively unknown.
By studying immune cells in the lung, researchers from the Institut Curie and Inserm have provided new knowledge on the subject. They reveal in particular that targeting ruptures in the nuclear envelope of these cells would represent a new opportunity for therapeutic intervention in diseases linked to age, particularly cancer (Cancer is a disease characterized by abnormal cell proliferation…), thus improving the quality of life (The quality of life of a population is a major issue in economic sciences and…) elderly people in the long term. Funded by the ARC Foundation, this work has just been published in the journal Nature Aging.
By studying immune cells in the lung, researchers from the Institut Curie (The Institut Curie is a foundation, whose main activities are on the one hand…) and Inserm have provided new knowledge on the subject.
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Age is one of the main risk factors for the development of numerous pathologies such as viral or bacterial infections, neurodegenerative diseases but also cancers. The economic and societal issues linked to the overall aging of the population constitute a major challenge. Furthermore, the notion of “healthy aging” increasingly suggests that targeting aging rather than its consequences is a much better strategy (The strategy – from the Greek stratos which means “army” and ageîn which means…) to reduce morbidity in the elderly population.
In France, more than two thirds of new cancers diagnosed occur in people aged over 65.[1]. The appearance of cancers with age is explained in particular by the accumulation of genetic alterations over the course of life, less effective DNA repair mechanisms, but also by an aging immune system with diminished protective functions. (immunsenescence). What are the mechanisms that govern this phenomenon? How can we develop new strategies to counteract immunosenescence?
The nucleus of immune cells sensitive to deformation
These are the questions that scientists from Inserm and the Curie Institute tried to answer. Over time, DNA becomes fragile and one of the characteristic markers of cell aging is genomic instability. However, when they patrol the different tissues of the body, the cells of the immune system are sensitive to deformations which weaken 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 ruptures of the nuclear envelope lead to DNA damage. It is essential to fully understand the processes at play at this level because they promote not only the aging of the organism but also the development of cancers. 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”, explains Dr Nicolas Manel, research director (Scientific research refers in firstly all the actions undertaken with a view to…) at Inserm and team leader at the Institut Curie.
Microscopy observation (Microscopy is the observation of a sample (placed in a microscopic preparation…) “2-photons” of the extreme deformation of an alveolar macrophage, during its passage between two alveoli. During These migrations, the nucleus also deforms, and this is when the DNA can be damaged.
A protein implicated in the lung: lamin A/C
At the Institut Curie, the Innate Immunity team of Dr Nicolas Manel, research director at Inserm, therefore studied a new experimental model in which the cells of the immune system are deficient in lamin A/C. The researchers examined a population of lung macrophages – alveolar macrophages – which are highly dependent on lamin A/C for their survival. 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 show severe signs of nuclear fractures and DNA damage, leading to a drastic reduction in their numbers in the lungs. Furthermore, surviving alveolar macrophages exhibit many similar characteristics to aged alveolar macrophages and accumulate markers characteristic of aging. The team also demonstrated that in the absence of lamin A/C in macrophages, the implantation (The word implantation can have several meanings:) and the growth of lung tumors is much more rapid, 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.
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