The Mitochondrial Genotype and Phenotype of Extreme Longevity

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Aging processes have been addressed from two different perspectives: Evolutionary Biology and Cellular Physiology (mechanistic approach). A clear identification of physiological and biochemical processes involved in setting the rate as well as the limits of aging, precludes the possibility of formulating a coherent and unified theory. Among the different mechanistic hypotheses of aging, the mitochondrial oxidative stress theory of aging is probably the most supported. Whether or not this hypothsis is true, a large consensus exists on mitochondria being a hub of metabolic processes involved in aging. My research program, which has been supported by NSERC (Discovery) for more than two decades, is dedicated to document evolutionary plasticity of mitochondrial structure and functions in the animal kingdom and to scrutinize the role and importance of mitochondrial DNA evolution in metabolic adaptation to specific environments and conditions. I recently focused on implication of mitochondria in the modulation of life span. I chose a comparative approach using bivalves as an animal model. This model includes the longest-lived complex animal species on earth, Arctica islandica, which can reach 507 years. This record has been obtained by an individual from an Icelandic population. In other populations from the North Atlantic (Europe and North America), the maximum life span can vary between 40 years to 200-300 years. Other taxonomically close species have maximum life span ranging from a few years to close to 150 years. I therefore have access to a two-dimensional comparative model: comparison of different species within a wide range of maximum life spans (from 4 years to 507 years), and comparison of different populations of A. islandica characterized by standard maximum life span ranging from 35 to 400 years (see Blier et al. Seminars in Cell and Developmental Biology, 2017). We previously observed a clear link between mitochondrial membrane robustness to oxidative stress (expressed as fatty acid content and Peroxidation Index) ROs management and the maximum lifespan in marine bivalves (Munro & Blier, 2012). We also demonstrated that mitochondria from the long-lived species generate a much lower efflux of H2O2 than short-lived species ( Munro et al. 2013). Based on these observations, we will deepen our analysis on the link between structure and function of mitochondria and longevity in animals. Some hypotheses have been put forward to link mitochondrial structure and function to lifespan and the aging process. Among them, 1) decline in the regulation of mechanisms of apoptosis induction 2) impairment of ROS management 3) instability of the Electron Transport System (ETS) supercomplexes. My students, trainees and I will characterize the fine structure of mitochondrial membranes (lipidomique analysis of membranes: phospholipids, sterols, cardiolipin content and structure) and stress responses.