PorteursAlexandre How KitAffiliation porteursFondation Jean Dausset - CEPH, Paris

Association of germline variants, somatic mutations and DNA methylation of the mitochondrial genome to human longevity

One of the greatest societal, economic and public health challenges in Europe in the near future concerns the aging of its population. The implication of mitochondria  has been studied in longevity due the role of these maternally inherited organelles in metabolic senescence mechanisms through oxidative phosphorylation and cell metabolism. Somatic mutations where shown to occur in the mitochondrial genome (mtDNA) at a high rate and the coexistence of mutated and wild-type form a mosaicism (heteroplasmy) that increases over the lifespan. There is also evidence of variations of mtDNA methylation between healthy and affected individuals in different pathologies such as cardiovascular, liver and cancer diseases.

The overall goal of the project is to analyze the  heteroplasmies and DNA methylation of the mitochondrial genome of French nonagenarians, centenarians and supercentenarians of the CEPH Aging cohort and their offspring. The project aims to identify the genetic and epigenetic variations of mtDNA associated with and potentially responsible for the human longevity as well as their transgenerational inheritance.