Mechanisms of exceptional longevity in the world's longest-lived animal

该项目将调查世界上最长寿的动物--双壳类软体动物--海洋乳猪--异常长寿背后的机制。这将通过评估三种可能的衰老机制来实现，这些机制在对传统的较短寿命物种(如线虫、果蝇和啮齿动物)的调查中被建议用来确定寿命。这些机制将在海洋夸克和其他6种寿命较短的双壳类物种中进行研究。这些物种的寿命跨度很大，从一个物种的寿命不到一年，到海洋中的袋鼠寿命超过400年。我们的总体假设是，所提出的一种或多种衰老机制将解释在双壳类中观察到的巨大的寿命范围。人口老龄化使得研究提高健康寿命的潜在疗法变得尤为及时，具有重大的社会和经济意义。利用经典的模式生物(如果蝇和啮齿动物)，我们对衰老过程的理解已经取得了重大进展。尽管这些生物具有优势，但选择它们主要是为了方便，而不是为了与人类衰老相关的特定特征。另一种方法是利用自然界普遍存在的惊人的多样性衰老速度，对寿命较短、衰老程度较低的物种与其他寿命较长的物种(即衰老较慢的物种)进行比较研究。后者在抵抗衰老过程方面显然是成功的，并可能对实现长寿的机制产生新的见解。双壳类软体动物(如蛤、扇贝和牡蛎)几乎被老龄研究人员忽视了，尽管它们在研究衰老方面具有明显的优势。具体地说，在大多数双壳类中，个体的准确年龄通常可以通过贝壳上或壳内的生长结构来确定。作为这一特征的结果，我们现在了解到，双壳类之间存在着巨大的寿命范围(从1岁到400岁)，这在任何其他动物群体中都是闻所未闻的。在许多地方可以从自然种群中获得大量的个体，由于它们的商业重要性，许多双壳类物种作为食物来源，其养殖技术也很发达。因此，双壳类有可能成为有价值的信息丰富的调查工具，以揭示自然如何戏剧性地改变了寿命和健康寿命。拟议的项目涉及英国海洋生物学家(他们是双壳类生物、维护和年龄确定方面的专家)和美国老年研究人员(他们是衰老研究的分子和生化方面的专家)之间的独特合作。该项目设计涉及七个精心挑选的双壳类物种，跨越了一系列最长寿命，并批判性地评估了关于潜在决定物种寿命的机制的三个看似合理的假说。在拟议的研究中，我们将评估：1)线粒体(细胞动力植物)在最大限度减少有害活性氧产生的同时产生ATP(化学能)的效率是否是长寿的关键决定因素；2)蛋白质组的稳定性，即蛋白质抵抗损伤和‘展开’的能力，是否是长寿的关键决定因素；以及3)抵抗压力的能力是否是长寿的关键决定因素。这项工作不仅将为未来对长寿双壳类动物衰老的研究奠定基础，而且对包括人类在内的其他动物也具有普遍意义。尽管软体动物在解剖学上看起来与人类不同，但不同动物群体的衰老症状是相似的(例如，蠕虫和人的骨骼减少/肌肉随着年龄的增长而减少)；因此，双壳类衰老研究提供的见解将与整个生物老年学社区相关，并有助于指导未来的衰老研究。

The project will investigate the mechanisms behind the exceptional longevity displayed in the bivalve mollusc, the ocean quahog, which is the world's longest-lived animal. This will be achieved by evaluating three plausible mechanisms of aging which have been suggested to determine life span during investigations of the traditional shorter-lived species e.g. nematodes, fruit flies and rodents. These mechanisms will be investigated in the ocean quahog and 6 other shorter-lived bivalve species. These species span a range of longevities, from less than one year in one species to greater than 400 years in the ocean quahog. Our overall hypothesis is that one or more of the mechanisms of aging suggested will explain the enormous range of longevities observed in bivalves. The aging of human populations makes research into potential therapies to enhance a healthy life span particularly timely with dramatic social and economic significance. Significant advances in our understanding of the aging processes have been made using the classical model organisms (e.g. fruit flies and rodents). Despite the advantages of these organisms they have been primarily chosen for convenience, rather than for specific features pertinent to human aging. An alternative approach, taking advantage of the astounding diversity of aging rates prevalent in nature, is a comparative investigation of short-lived, poorly aging species with other long-lived species i.e. those that age slowly. These latter are demonstrably successful at resisting aging processes and might yield novel insights into mechanisms responsible for the achievement of a long life span. Bivalve molluscs (e.g. clams, scallops and oysters) have been virtually ignored by aging researchers despite their obvious advantages for investigating aging. Specifically, in most bivalves the precise age of an individual can usually be ascertained using growth structures on or within the shell. As a consequence of this feature, we now understand that there is an enormous range of longevities amongst bivalves (from <1 to >400 years), unheard of in any other animal group. Large numbers of individuals can be obtained from natural populations in many locations and because of their commercial importance many bivalve species as food sources, techniques for their culture are well-developed. Thus bivalves have the potential to become valuable informative investigative tools to reveal how nature has dramatically modified life- and health span. The proposed project involves a unique collaboration between marine biologists in the UK (who are experts in the biology, maintenance and age-determination of bivalves) and aging researchers in the USA (who are experts in molecular and biochemical aspects of aging research). The project design involves seven carefully selected bivalve species, spanning a range of maximum lifespans, and critically evaluating three plausible hypotheses about mechanisms which potentially determine the life span of a species. In the proposed research we will evaluate: 1) whether the efficiency of the mitochondria (the cellular power plants) at producing ATP (chemical energy) while minimizing the production of harmful reactive oxygen species is a critical determinant of longevity; 2) whether proteome stability, the ability of proteins to resist damage and 'unfolding', is a critical determinant of longevity and 3) whether the ability to resist stress is a critical determinant of longevity. This work will not only underpin future research into aging in long-lived bivalves but also have generic relevance for other animals, including people. Although molluscs appear anatomically different to humans, the symptoms of aging are similar across the animal groups (e.g. sarcopenia/muscle loss with age in worms and people); therefore insights provided by research into aging in bivalves will be of relevance to the whole biogerontology community and assist in directing future aging research.