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

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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.