The aim of the AgeMed research program is to decipher the cellular mechanisms of the aging process. The aim is to identify cellular signaling pathways and molecular targets, which will subsequently enable the development of innovative medical practices to prevent and cure age-related diseases.

Aging is a multifactorial process that leads to a progressive loss of regenerative capacity and tissue function while promoting the development of a variety of age-related diseases. There is evidence that one or more fundamental aging processes are responsible for these changes. Therefore, rather than treating age-related diseases as separate entities, it is necessary to intervene in these fundamental processes (e.g Senescence cellular, immunosenescence, immune surveillance of senescent cells, progenitor cell aging, and neuronal aging) could revolutionize medicine and significantly alleviate the enormous individual and societal burden resulting from an ever-increasing elderly population.

It is precisely for this reason that Inserm’s AgeMed research program was launched in 2016. From 2017 to 2023, 15 research teams set out to decipher two main types of biological processes that lead to aging: cellular senescence and neuroaging.

Cell aging

Cell aging is a physiological process that leads to a change in cell functions and an irreversible stop in their division. And although it is well known that the accumulation of senescent cells in the body contributes to age-related diseases, there is still much to be understood about it. Therefore, a comprehensive description of the features associated with senescence of different cell types – in culture and in different tissues – in different physiological contexts (normal and stressful) is lacking. Likewise, the significance of the causal role of senescence in health, aging and age-related disorders is not known in detail.

Conducting such analyzes has been complicated by the difficulty of identifying senescent cells from tissues, monitoring, quantifying, purifying and pharmacologically eliminating their development, as well as obtaining complete data on the factors they secrete (secretome), as well as on their tissue and systemic Preserve environment. The AgeMed program has addressed some of these gaps by taking a multifaceted, integrated approach that combines systems biology and cutting-edge molecular techniques.

This work revealed the role of novel epigenetic, telomeric, metabolic and immunological pathways involved in the programming of senescent cells as well as in their paracrine effects and immunological elimination. Some of these results have already been published:

Further publications are being reviewed or prepared.

Thanks to these fundamental discoveries, therapeutic innovations have been developed to counteract the deleterious effects of senescence in three pilot pathologies: chronic obstructive pulmonary disease (COPD), Fibrosis pulmonary idiopathic and osteoarthritis. The results are still being revised for publication.

Neuroaging

Normal brain aging leads to progressive cognitive decline. During this process, one of the regions of the brain is most commonly affectedSeahorse. This brain structure plays a key role in the formation and consolidation of memory due to its impressive plasticity. However, this high degree of plasticity makes the hippocampus vulnerable to environmental influences (e.g. malnutrition), systemic factors (e.g. hormonal changes) and aging. And although we know that the effects of aging on this plasticity are linked to memory loss, the underlying cellular and molecular mechanisms remain largely unknown. Given increasing life expectancy and the increasing number of individuals potentially affected by age-related cognitive impairment, elucidating these mechanisms is more important than ever: their understanding could serve as a basis for the development of new therapeutic strategies and to respond to an urgent unmet medical need.

The AgeMed program has made it possible to study extracellular mechanisms (in which hormones are involved) and intracellular mechanisms (with a role for autophagy, Telomeres And Mitochondria) specific to the origin of the functional decline observed with age. Some of these results have already been published:

Further publications are being reviewed or prepared.

These findings pave the way to targeting neuronal aging pathways, delaying cognitive decline and preventing the onset of neurodegenerative diseases.