The Mitochondrial Genotype and Phenotype of Extreme Longevity

衰老过程从两个不同的角度进行了研究：进化生物学和细胞生理学(机械论方法)。明确确定衰老速度和极限所涉及的生理和生化过程，排除了形成一个连贯和统一的理论的可能性。在衰老的不同机制假说中，线粒体氧化应激衰老理论可能是最受支持的。无论这一假设是否属实，线粒体是参与衰老的新陈代谢过程的中心，这一点已经达成了很大的共识。我的研究项目由NSERC(发现)支持了20多年，致力于记录动物王国中线粒体结构和功能的进化可塑性，并仔细研究线粒体DNA进化在代谢适应特定环境和条件中的作用和重要性。最近，我专注于线粒体在调节寿命中的作用。我选择了一种比较的方法，使用双壳类作为动物模型。这个模型包括地球上最长寿的复杂动物物种--岛牛，它可以活到507岁。这一记录是由一名个人从冰岛人口中获得的。在北大西洋(欧洲和北美)的其他种群中，最长寿命可以从40岁到200-300岁不等。其他在分类上相近的物种的最大寿命从几年到近150年不等。因此，我可以使用二维比较模型：比较最长寿命范围很广(从4岁到507岁)的不同物种，以及比较以标准最长寿命为35岁到400岁的不同种群(见Blier等人)。2017年细胞与发育生物学研讨会)。我们以前观察到海洋双壳类中线粒体膜对氧化应激(以脂肪酸含量和过氧化指数表示)的稳定性、ROS管理和最长寿命之间存在明显的联系(Munro&Blier，2012)。我们还证明了长寿物种的线粒体比短寿物种产生的过氧化氢外流要低得多(Munro等人。2013)。基于这些观察，我们将深化我们对线粒体结构和功能与动物寿命之间的联系的分析。已经提出了一些假设，将线粒体的结构和功能与寿命和衰老过程联系起来。其中，1)诱导细胞凋亡机制的调节功能减弱，2)ROS管理功能受损，3)电子传输系统(ETS)超复合体的不稳定性。我的学生、学员和我将描述线粒体膜的精细结构(膜的脂类分析：磷脂、甾醇、心磷脂的含量和结构)和应激反应。

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.**