From a biological viewpoint, the function-centred approach recommended by WHO represents a challenge due to the multidimensionality that characterizes intrinsic capacities’ trajectories during aging.
Therefore, to better appraise the functional construct, INSPIRE will develop an integrative view of biological aging. Three classes of parameters transversal to the whole organism, present in all organs and strongly interrelated are crucial in this tissue homeostasis: inflammation and immunity that represents both a warning signals and the house keeping guard of tissue integrity, mesenchymal stem/stroma cells (MSC) allowing support for all function and their adaptation and metabolism that controls any cell decision and the fate of most of them. In top of that senescence both at the level of the cell or the whole organism is a common mechanism involved in many aspect of aging.
The scientific projects resulting from these general objectives are based either on a priori approaches resulting from results already obtained by the partner laboratories; or on non-supervised approaches involving strong collaborations between research centers with complementary skills.
These projects will be based on the various INSPIRE cohorts (human and animals), some examples are given thereafter.
On Stromal Cells
1st project: Demonstrate a stromal cell signature specific of biological aging and frailty
- Know more about this project on stromal cells
On Immunity and inflammation
- The projects aim to better characterize at the cellular and molecular levels the correlates of immune-senescence and inflammaging to pinpoint the pathways associated with specific immune alterations during biological aging
- Identification of a specific myeloid signature to predict inflammatory status during frailty phenotype
- Identification of targetable molecules causally involved in age-related immune cell defects
- Role of age-associated B cells in humoral immunity
- Functional characterization of dendritic cell functions in the course of aging
- Hepatitis E Virus genotype 3 infection in the elderly and immune response
- Behavioral assessment of the impact of aging, neurodegeneration and brain infections (Supported by the Fondation Recherche Médicale /France Alzheimer)
- Identify specific metabolic biomarkers for frailty
- Urinary peptidome signatures as non-invasive detection of frailty
- Effects of metabolic dysfunction and chronic kidney disease on arterial endothelial cell morphology during aging
- Prevention of multi-organ premature aging through mitochondria-targeted strategies
- MOVE ON project
- Determine the changes in brain insulin signaling in aging (The INS2BRAIN project)
- Inspire SPHERES: role of fat cell lipid droplet in aging-related cardiometabolic diseases (Founded by an ERC Synergy program)
- MONA: Metabolism, obesity, nutrition and age
- A role for transposable elements deregulation in T cell ageing and immunosenescence
- Role of prominin 2 as biomarker of cardiac aging
- Effects of Time Restricted Feeding and senolytics on the onset of frailty
- Oral biosensors as new biomarkers to characterize frailty and biological aging
- Skin and aging (Supported by Pierre Fabre Dermo Cosmetic). The project is focused on the biology of skin aging
- Project AD Frail: Allogenic cell therapy to treat frailty and Alzheimer Disease (AD): Phase I/II (Supported by a national grant PHRC)