AgeMed: Understanding Aging Mechanisms to Better Fight Them

Science

Launched in 2016, AgeMed is one of Inserm’s three cross-cutting scientific programs. It is devoted to aging, a subject that has become crucial in public health, and aims to bring a French scientific community together around collaborative projects on the subject.

Aging is an age-old issue, but biologists and doctors have only recently begun to try to fight it. We are experiencing a true explosion of new concepts in the area,” states Éric Gilson, who heads the Institute for Research on Cancer and Aging (IRCAN, Inserm unit 1081/CNRS/Université Nice Sophia Antipolis, Nice). The researcher has long been working on telomeres, those sequences located at the ends of chromosomes that shorten over time, with each cell division. Naturally, he became interested in aging, to the point that he founded IRCAN in 2012. In his words, it was “the first institute to combine the themes of aging and cancer.” Since 2016, he has also been in charge of the scientific coordination of a cross-cutting program (see inset) in which twenty Inserm teams participate: the AgeMed program, which stands for from AGEd cells to MEDical applications.

Old age is a major risk factor for cancer and chronic pathologies (neurodegenerative and cardiovascular diseases, osteoporosis, type 2 diabetes, pulmonary or hepatic fibrosis, and so on). In 2050, in France and in comparable nations, one out of three inhabitants will be at least sixty years old. To be able to prevent and/or effectively manage the age-related illnesses that these people risk developing, the mechanisms of aging must be better understood. That is the primary objective of the AgeMed program. In particular, it aims to determine how known – or partially known – cellular mechanisms manifest as aging in organs and in the body as a whole.

Senescent Cells and Aging Cells...

Today, our understanding of the phenomenon of senescence is solid. It is the state that a cell ends up acquiring after an accumulation of all kinds of stress: heat, radiation, free radicals, lack of or excess food, drugs, pollutants, or an excessive number of divisions. When it can neither repair the damage nor kill itself, the cell changes shape and function. More importantly, it loses its ability to divide. “Experimental results show that this cellular phenomenon reflects one or more aspects of aging in the body. For the first time, we are catching a glimpse of an aging mechanism that is shared by all organs,” points out Gilson. AgeMed will seek to better determine the causes and timeline of senescence, and to better understand how the body eliminates – or fails to eliminate – these cells. The accumulation of senescent cells in the tissues does seem to contribute to some age-related illnesses.

A second, more exploratory focus is on cells deemed to be aged. “We have good reason to think that, for some cell types, aging does not involve senescence. This applies in particular to cells that do not divide, such as neurons, muscle cells, or retinal cells,” explains the researcher. Aged cells have a modified energy metabolism and are not as good at controlling the quality of the macromolecules that they are constantly producing. The teams involved in studying this are focusing on neural aging with the hope of better tackling neurodegenerative diseases such as Parkinson’s, Alzheimer’s, or Huntington’s.

Modeling for Understanding and Action

The third main focus will be on computer modeling of cell mechanisms, in partnership with Dassault Systèmes. If the models turn out to be sufficiently predictive, they may also be used to indicate therapeutic targets or predict the action of potential drugs. Manufacturers have already expressed their interest.

Inserm’s Cross-cutting Scientific Programs

Inserm recently launched three cross-cutting programs on three emerging topics that are considered high-priority due to their repercussions on public health:

After a call for tenders from Inserm’s teams and a selection of projects by an international jury, the aim is to pull together research communities on a given subject. The three consortia created as a result are open to academic and industrial partnerships. All of them are devoting a portion of their work to modeling/simulation with Dassault Systèmes (3DS). The research, which will be serve as a foundation at first, will allow for the creation of public-private partnerships once the prospects for application emerge.

One year after its launch, AgeMed met its initial objectives with ten publications and three patents filed. “One of the virtues of this cross-cutting program is that it brought out a French scientific community in the aging field. Such communities already exist in countries like Germany, the United Kingdom, and the U.S.” Gilson would now like to expand this community. “In late 2018 or early 2019, we will be holding an encounter open to any interested team.” In his opinion: “This program must benefit French research as a whole.”