The Mitochondrial Genotype and Phenotype of Extreme Longevity

衰老过程已经从两个不同的角度解决：进化生物学和细胞生理学（机制方法）。对确定衰老速度和极限所涉及的生理和生化过程的明确认识，排除了制定连贯统一理论的可能性。在不同的衰老机制假说中，线粒体氧化应激理论可能是最受支持的。无论这一假设是否正确，线粒体是参与衰老的代谢过程的中心，这是一个很大的共识。我的研究项目得到了NSERC （Discovery）二十多年的支持，致力于记录动物王国线粒体结构和功能的进化可塑性，并仔细研究线粒体DNA进化在对特定环境和条件的代谢适应中的作用和重要性。我最近集中研究了线粒体在调节寿命中的作用。我选择了比较的方法，用双壳类动物作为动物模型。这个模型包括地球上最长寿的复杂动物物种——北极岛，其寿命可达507年。这个记录是由一个冰岛人创造的。在北大西洋（欧洲和北美）的其他种群中，最长寿命可在40年至200-300年之间变化。其他分类学上相近的物种的最长寿命从几年到接近150年不等。因此，我可以使用二维比较模型：比较最大寿命范围（从4年到507年）内的不同物种，比较标准最大寿命范围从35年到400年的a . islandica的不同种群（见Blier et al.）。细胞与发育生物学研讨会，2017)。我们之前观察到，在海洋双壳类动物中，线粒体膜对氧化应激（以脂肪酸含量和过氧化指数表示）的稳健性和活性氧管理与最长寿命之间存在明确的联系（Munro & Blier, 2012）。我们还证明，与短命物种相比，长寿物种的线粒体产生的H2O2外排量要低得多（Munro et al. 2013）。在此基础上，我们将进一步深入分析动物线粒体的结构和功能与寿命之间的联系。一些假说认为线粒体的结构和功能与寿命和衰老过程有关。其中，1)凋亡诱导机制的调控下降2)ROS管理的损害3)电子传递系统（ETS）超配合物的不稳定性。我的学生、学员和我将描述线粒体膜的精细结构（膜的脂质组学分析：磷脂、固醇、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.