Immunometabolism as a driver of senescence and aging
Speaker: Maria Mittelbrunn, PhD - Centro de Biología Molecular Severo Ochoa – CSIC – UAM – Instituto de Investigación del Hospital 12 de Octubre – Madrid - Spain
Organizer: IRB Barcelona
Date: Wednesday 19 September, 13:00h
Place: Aula Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Manuel Serrano, PhD
Mitochondrial dysfunction is a hallmark of aging. Our aim is to characterize how perturbations of mitochondrial function, specifically in cells of the immune system, affect organism homeostasis and lifespan. To explore this hypothesis, we are using a mouse model whose mitochondrial function is compromised by deletion of mitochondrial transcription factor Tfam, specifically in T lymphocytes. The absence of Tfam induces a severe decrease in mtDNA content resulting in severe mitochondrial dysfunction and impaired oxidative phosphorylation, thus forcing a metabolic switch towards glycolysis. Glycolytic T cells acquire proinflammatory features provoking a cytokine storm resembling inflammaging characterized by high serum levels of IL6, TNF, and IFN-. CD4Tfam-/- mice display reduced body weight, kyphosis, altered glucose homeostasis, sarcopenia, and cardiovascular alterations. On the whole, CD4Tfam-/- mice serve as an innovative genetic model for frailty and premature aging, reflecting the importance of tight immunometabolic control in preventing sterile inflammation and delaying aging and the onset of age-associated diseases.
Molecular Medicine Programme Seminar