Cédric Dray / Armelle Yart
During lifespan, environmental fluctuations consistently forced organism and cells to develop metabolic flexibility in order to maintain their energy homeostasis.
In this context, many aspects of cellular/tissue metabolism changes are driven by redox metabolism as well as inter-cellular and inter-organs metabolic interactions that are fundamental to maintain tissue and whole body energetic homeostasis. Altogether, these parameters are in constant adaptation and represent the metabolic resilience of cell (cell capacity to face metabolic alterations).
We hypothesized that metabolic resilience directs the ability of the aging organism to maintain the main metabolic functions (storage, utilization and release of energy) necessary to perform towards healthy-aging or dependence when disrupted.
Our aim is to investigate the role and the regulation of local/systemic metabolic dialogue within a tissue (mesenchyma/parenchyma) and between metabolic tissues (adipose tissues/muscle/liver) by focusing on intracellular changes in metabolic pathways and redox state triggering major modifications of secretion and cell production. This will allow identifying new mechanisms that contribute, when defective, to the onset or aggravation of age-related diseases (sarcopenia, metabolic diseases) that could represent therapeutic targets of interest.
Metabokines and age-related loss of function
Inter-cellular and inter-organs metabolic interactions are fundamental to maintaining tissue and whole body energetic homeostasis. The effectors mediating these metabolic interplays include both hormones/cytokines and metabolites (gathered under the term “metabokines”), the latter being able to act either as nutrients or signaling molecules.
During aging, these changes of “metabokines” profile could interfere with the dialogue between metabolic tissues such as adipose tissues, muscle and liver and consequently support the decline of metabolic flexibility during aging.
Therefore, the impact of aging on the overall distribution of “metabokines” fluxes remains to be fully described. To that aim, we are developing new models of accelerated of early aging (Nothobranchuis Furzeri, genetic diseases, nutritional input) combined to state-of-the-art approaches (fluxomics, organ-on-chip) able to identify and target new pathways and therapeutic candidates.
L'état redox, un nouveau déclencheur du vieillissement
Using up to date experimental animal models and human resources, we are establishing the link between age-related loss of metabolic functions and redox state and are studying the causes and consequences of metabolic flexibility alterations during aging in metabolic tissues.
Many aspects of cellular/tissue metabolism are driven by redox metabolism, which corresponds to a complex network of electron transfer. The maintenance of redox homeostasis is of paramount importance for normal cell and tissue functions and increasing evidences demonstrate that the redox state is the main conductor regulating the metabolic reorganization during stress, which is enabled by functional metabolic flexibility.
In addition to support energy homeostasis, redox state drives many cellular functions including cell proliferation, differentiation, senescence as well as autocrine/paracrine/endocrine activity. While redox stress is well known to be associated with aging, Metabolink aims to understand and to target the network and the dynamics of the metabolic and redox reorganizations associated with aging and age-associated pathologies.
Ageing, friality, cancer, redox metabolism, hypoxia, metabolic flexibility, lipids, fibroblasts, mesenchymal stem cells
Molecular biology, cell culture ( mouse/human; normoxia/Hypoxia), flux cytometry
Redox metabolism, Mitochondria, ROS, Adipose tissue, Plasticity, brite and brown adipocytes, Lactate sensing and signaling
Ageing, haptoglobine, sarcopenia, senescence
Fluxomic, metabolomic HR-MS analysis, data processing
Apelin, sarcopenia, ageing, adipokines, myokines, metabolism
Redox metabolism, metabolic challenge, human biological diagnostic, human nutrition, coenzymes
Metabolism, adipocytes, metabolomic, fluxomic, isotopic tracing in vitro/in vivo, cell culture (hypoxia), mitochondrial activity
Metabolism, adipose tissue, apelin, adipokines, obesity, type 2 diabetes
Noonan syndrom, hormones, metabolism and muscle physiology, inter-organ communication
In vivo functional exploration, metabolic phenotyping, surgery
Sophie Le Gonidec
Anesthesia, reanimation, pain
Ageing, sarcopenia, Zebrafish, mitochondrial metabolism
Cognition, obesity, adipose tissue
Apelin/APJ, obesity, adipokines, diabetes, ageing
Mass spectrophometry Fluxomic, Metabolomic
Liver, adipose tissue, macrophages, metabolism, inflammation, ageing
metabolism, metabolic network, metabolomic, fluxomic, metabolic modelisation
Surgery, cognition, obesity, adipose tissue, inflammation
Growth, bone, metabolism, endocrinology, rare diseases, translationnal research
Metabolism, adipocytes, metabolomic, fluxomic, isotopic tracing in vitro/in vivo, cell culture, mitochondria activity
Metabolism, rare diseases, translational research, signalisation, senescence
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