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Novel therapeutic interventions in age-related and neurodegenerative diseases.

The brain is particularly vulnerable to the effects of aging, leading potentially to memory loss, cognitive impairments, mood changes and neurodegeneration. The incidence of dementia- and neurodegeneration-related disorders is predicted to dramatically increase in the next decades- and is already on the rise- due to increased human lifespan in our current society. Therefore, the identification of therapeutic interventions to combat, delay or even reverse cognitive decline is imperative. 

Our major objective is to discover intrinsic mechanisms underlying brain aging and to identify molecules and blood factors that combat age-related brain deterioration and memory loss through translational approaches. Specifically, our research centers on three axes:

  • Decipher the intrinsic mechanisms of cognitive aging: we focus on the processes that take place either due to the passage of time (normal/physiological aging) or due to physiological alterations due to disease (depression, pathology). 
  • Develop technological tools to understand brain aging: we have developed brain-on-chip models that mimic the effect of aging on the endothelial and blood-brain-barrier and use these technologies to test blood factors and drugs
  • Discover rejuvenating and pro-aging blood factors and biomarkers: using the blood proteome as a source and indicator of accelerated aging or disease, we aim to identify biomarkers specific for aging and disease to use in the development of diagnostic and therapeutic tools.

Our group is support by: Agence Nationale pour la Recherche, Fondation Deniker, Agemed, Inserm, Université Paris Cité, Association de Prévoyance Santé and Emulate.


 

Key publications
Moigneu C, Abdellaoui S, Ramos-Brossier M, Pfaffenseller B, Wollenhaupt-Aguiar B, de Azevedo Cardoso T, Camus C, Chiche A, Kuperwasser N, Azevedo da Silva R, Pedrotti Moreira F, Li H, Oury F, Kapczinski F, Lledo PM, Katsimpardi L. Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy. Nat Aging. 2023; Feb;3(2):213-228. Erratum in: Nat Aging. 2023 Aug;3(8):1036. doi: 10.1038/s43587-022-00352-3. PMID: 37118117 ; PMCID: PMC10154197.
Siopi E, Chevalier G, Katsimpardi L, Saha S, Bigot M, Moigneu C, Eberl G, Lledo PM. Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine. Cell Rep. 2020; Mar 17;30(11):3682-3690.e6. doi: 10.1016/j.celrep.2020.02.099. PMID: 32187541 .
Katsimpardi L, Kuperwasser N, Camus C, Moigneu C, Chiche A, Tolle V, Li H, Kokovay E, Lledo PM. Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice. Aging Cell. 2020; Jan;19(1):e13038. doi: 10.1111/acel.13038. PMID: 31637864 ; PMCID: PMC6974718.
Lazarini F, Katsimpardi L, Levivien S, Wagner S, Gressens P, Teissier N, Lledo PM. Congenital Cytomegalovirus Infection Alters Olfaction Before Hearing Deterioration In Mice. J Neurosci. 2018; Dec 5;38(49):10424-10437. doi: 10.1523/JNEUROSCI.0740-18.2018. PMID: 30341181 ; PMCID: PMC6596252.
Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. 2014; May 9;344(6184):630-4. doi: 10.1126/science.1251141. PMID: 24797482 ; PMCID: PMC4123747.