The Mitochondrial Genotype and Phenotype of Extreme Longevity
长寿的线粒体基因型和表型
基本信息
- 批准号:RGPIN-2019-05992
- 负责人:
- 金额:$ 5.97万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2019
- 资助国家:加拿大
- 起止时间:2019-01-01 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.**
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(机械方法)。 要想清楚地确定衰老的速度和极限,就必须明确生理和生化过程,这就排除了建立一个连贯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。 无论这一假设是否正确,线粒体是衰老过程中代谢过程的中心,这一点已达成共识。我的研究计划,这已经由NSERC(发现)支持了二十多年,致力于记录线粒体结构和功能在动物王国的进化可塑性,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。我最近专注于线粒体在寿命调节中的意义。我选择了一种比较的方法,使用双壳类作为动物模型。该模型包括地球上最长寿的复杂动物物种Arctica islandica,可达507岁。这一记录是由一个冰岛人获得的。在北大西洋(欧洲和北美)的其他种群中,最大寿命可以在40岁到200-300岁之间变化。其他分类学上接近的物种的最大寿命从几年到近150年不等。因此,我有机会获得一个二维的比较模型:比较不同物种的最大寿命范围(从4年到507年),并比较不同种群的A。islandica的特点是标准的最大寿命范围从35到400年(见Blier et al. Seminars in Cell and Developmental Biology,2017)。我们先前观察到线粒体膜对氧化应激的鲁棒性(表示为脂肪酸含量和过氧化指数)RO管理与海洋双壳贝类的最大寿命之间存在明确的联系(Munro & Blier,2012)。我们还证明,长寿物种的线粒体产生的H2 O2流出量远低于短命物种(Munro等人,2013)。基于这些观察,我们将深入分析线粒体的结构和功能与动物寿命之间的联系。 已经提出了一些假设,将线粒体结构和功能与寿命和衰老过程联系起来。其中,1)凋亡诱导机制的调节下降2)ROS管理的损害3)电子传递系统(ETS)超复合物的不稳定性。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、心磷脂含量和结构)和应激反应。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Blier, Pierre其他文献
Effects of Sustained Administration of Quetiapine Alone and in Combination with a Serotonin Reuptake Inhibitor on Norepinephrine and Serotonin Transmission
- DOI:
10.1038/npp.2012.18 - 发表时间:
2012-06-01 - 期刊:
- 影响因子:7.6
- 作者:
Chernoloz, Olga;El Mansari, Mostafa;Blier, Pierre - 通讯作者:
Blier, Pierre
Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain
- DOI:
10.1038/npp.2012.140 - 发表时间:
2013-01-01 - 期刊:
- 影响因子:7.6
- 作者:
Chenu, Franck;El Mansari, Mostafa;Blier, Pierre - 通讯作者:
Blier, Pierre
Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion
- DOI:
10.1007/s00213-011-2260-1 - 发表时间:
2011-09-01 - 期刊:
- 影响因子:3.4
- 作者:
Ghanbari, Ramez;El Mansari, Mostafa;Blier, Pierre - 通讯作者:
Blier, Pierre
Synergistic effect of aripiprazole and escitalopram in increasing serotonin but not norepinephrine neurotransmission in the rat hippocampus
- DOI:
10.1016/j.neuropharm.2018.11.006 - 发表时间:
2019-03-01 - 期刊:
- 影响因子:4.7
- 作者:
Ebrahimzadeh, Mohammad;El Mansari, Mostafa;Blier, Pierre - 通讯作者:
Blier, Pierre
Rational site-directed pharmacotherapy for major depressive disorder
- DOI:
10.1017/s1461145713000400 - 发表时间:
2014-07-01 - 期刊:
- 影响因子:4.8
- 作者:
Blier, Pierre - 通讯作者:
Blier, Pierre
Blier, Pierre的其他文献
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{{ truncateString('Blier, Pierre', 18)}}的其他基金
The Mitochondrial Genotype and Phenotype of Extreme Longevity
长寿的线粒体基因型和表型
- 批准号:
RGPIN-2019-05992 - 财政年份:2022
- 资助金额:
$ 5.97万 - 项目类别:
Discovery Grants Program - Individual
The Mitochondrial Genotype and Phenotype of Extreme Longevity
长寿的线粒体基因型和表型
- 批准号:
RGPIN-2019-05992 - 财政年份:2021
- 资助金额:
$ 5.97万 - 项目类别:
Discovery Grants Program - Individual
Caractérisation des polyamines de la laitance de hareng et validation des propriétés bioactives sur culture cellulaire
哈伦浮层多胺的表征和细胞培养物生物活性物质的验证
- 批准号:
530893-2018 - 财政年份:2020
- 资助金额:
$ 5.97万 - 项目类别:
Collaborative Research and Development Grants
Les mitochondries comme cibles pharmacologiques ou nutritionnelles pour atténuer l'induction des réponses inflammatoires à la Covid-19
线粒体与 Covid-19 炎症反应的药理学或营养学相关
- 批准号:
555144-2020 - 财政年份:2020
- 资助金额:
$ 5.97万 - 项目类别:
Alliance Grants
The Mitochondrial Genotype and Phenotype of Extreme Longevity
长寿的线粒体基因型和表型
- 批准号:
RGPIN-2019-05992 - 财政年份:2020
- 资助金额:
$ 5.97万 - 项目类别:
Discovery Grants Program - Individual
Caractérisation des polyamines de la laitance de hareng et validation des propriétés bioactives sur culture cellulaire
哈伦浮层多胺的表征和细胞培养物生物活性物质的验证
- 批准号:
530893-2018 - 财政年份:2019
- 资助金额:
$ 5.97万 - 项目类别:
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Déterminants mitochondriaux de la longévité: interactions génomiques et phénotypiques
长寿的线粒体决定因素:基因与表型的相互作用
- 批准号:
155926-2011 - 财政年份:2018
- 资助金额:
$ 5.97万 - 项目类别:
Discovery Grants Program - Individual
Prédicteurs métaboliques et physiologiques de la réponse au stress chez les poissons
泊松应激反应的代谢和生理学预测
- 批准号:
494551-2016 - 财政年份:2018
- 资助金额:
$ 5.97万 - 项目类别:
Strategic Projects - Group
Déterminants mitochondriaux de la longévité: interactions génomiques et phénotypiques
长寿的线粒体决定因素:基因与表型的相互作用
- 批准号:
155926-2011 - 财政年份:2017
- 资助金额:
$ 5.97万 - 项目类别:
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Prédicteurs métaboliques et physiologiques de la réponse au stress chez les poissons
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- 资助金额:
$ 5.97万 - 项目类别:
Strategic Projects - Group
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