On the strength of its national initiatives, Inserm has recently launched an international collaboration program to reinforce knowledge in the field of aging... The objective being twofold: to understand how our cells age and to provide new avenues for staying healthy for longer.
Is aging a partially programmed process or the result of chaotic events that lead to our organs not working as well as they should? Hotly debated in the scientific community, this question is fundamental to knowing whether the aging of our body and the diseases related to aging have biological factors in common. However, in order to explore such a vast research topic, the involvement of a wide variety of disciplines is crucial. That is why Inserm decided in 2016 to initiate a cross-cutting program dedicated to aging, « to bring about the emergence of a research community,” explains its scientific coordinator Éric Gilson*. Since then, some twenty French research laboratories have collaborated through the program AgeMed (from AGed cells to MEDical applications). « Very quickly, the various teams built cooperation programs enabling progress on both the basic and clinical levels,”, he emphasizes.
Understanding cell senescence
One year away from its conclusion, AgeMed is looking to be extremely fruitful. For example, it has shown how the dynamic regulation of certain genes leads a cell to become senescent: « Cells that are able to regenerate, such as those of the skin, blood, or intestinal wall, accumulate marks of stress over time. For example, their telomeres (the ends of chromosomes) shorten, their chromatin is modified, the factors regulating gene expression are disrupted… This all leads to their senescence. However, one of the teams participating in AgeMed, at Institut Pasteur in Paris, has shown this phenomenon to be the result of a series of events that are programmed in the young cell by an epigenetic mechanism, » says Gilson. On a more clinical level, therapeutic avenues followed by Serge Adnot’s team at Henri-Mondor Hospital in Créteil are already arising from this discovery: « This research has led to the identification of transcription factors that coordinate senescence. Inhibitors are being developed to slow this aging mechanism and the diseases in which cell senescence is involved. »
The research carried out as part of AgeMed has also made it possible to understand how other cells – those that do not regenerate (neurons, muscle cells, etc.) – change over time. « We are seeing the modification of certain cell functions. In neurons, for example, Franck Oury’s team at the Necker-Enfants Malades Institute in Paris has shown that age-related cognitive decline appears to be associated with reduced capacity for autophagy, » continues Gilson. In other words, this mechanism for recycling damaged cell material is increasingly less efficient, leading to the harmful crowding of damaged molecules in aging neurons. « This type of discovery also opens the door to new therapeutic avenues, with a search for molecules to restore efficient autophagy. »
An international network
To give international exposure to this French expertise, Inserm launched in October 2021 a Thematic Coordination Program (TCP) on aging: InterAging. The idea of such programs is to build strong thematic international cooperation, with countries whose expertise complements that available in France. InterAging is the first TCP set up by Inserm. The Institute makes € 750,000 available to the international network established (over 5 years), in order to fund four joint dissertations that will bridge the gap between a French laboratory and a foreign laboratory, as well as the exchanges and interactions that will take place between all the program’s teams. The corresponding laboratories are located in Singapore, Germany, China and soon in the UK. « The timing is remarkable, smiles Gilson. Inserm has taken the lead on this cutting-edge theme, with teams that are now working as part of a network and which know each other well. Thanks to this new international momentum, the prospects are endless. »
* Professor of Cell Biology at the Faculty of Medicine of Nice; Director of the Institute for Research on Cancer and Aging (IRCAN), unit 1081 Inserm/CNRS/Université Côte d’Azur