SA6 044 AGEING IS NO LONGER AN UNSOLVED BIOLOGICAL PROBLEM (SUPPORTED BY THE ELLISON MEDICAL FOUNDATION AND CO-SPONSORED BY THE GERONTOLOGICAL SOCIETY OF AMERICA)

SA6 044-1 THE CAUSES OF BIOLOGICAL AGEING ARE KNOWN

L. HAYFLICK - University of California, San Francisco (The Sea Ranch, CA, United States of America)

The finitude of life is divided into aging, longevity determination, age associated diseases and death. The efficacy of repair and turnover systems is favored over molecular dysfunction until reproductive maturation when the balance slowly shifts in favor of accumulating dysfunctional molecules caused by increasing entropy (dispersal of energy) and resulting in the aging phenotype. The molecules that compose repair and turnover systems also suffer the same fate as do their substrate molecules. It is these maintenance systems that are the determinants of longevity. The genome indirectly governs the anabolic determinants of longevity. This is fundamentally different from the stochastic, catabolic processes of aging. Age changes simply increase vulnerability to age-associated diseases.

SA6 044-2 UNDERSTANDING THE BIOLOGICAL REASONS FOR AGEING

R. HOLLIDAY - The Australian Academy of Science (Canberra, Australia)

A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum lifespans. It has become apparent that the best strategy for animals’ survival is to develop to an adult and reproduce, but not to invest resources in maintaining the soma indefinitely. There is a trade-off between the investment of resources in reproduction, and the survival time of the soma. At a stroke, this solves the problem of different rates of ageing in different species, because those that develop and reproduce fast have short lifepans, and those that develop and reproduce slowly have long lifespans. This difference is due to the resources invested in the maintenance of the adult soma. There is much evidence that the efficiency of maintenance correlates with maximum longevity. Thus, ageing can be defined as the eventual failure of maintenance. It has also become evident that there are many maintenance mechanisms, and these depend on very many genes, and the investment of considerable metabolic resources. A broad interpretation of the different degenerative changes during ageing should be adopted, with the general conclusion that ageing is multi-causal.

SA6 044-3 AGEING IS SOLVED BUT ITS SOLUTION ALSO HIGHLIGHTS ITS COMPLEXITY - GEARING UP FOR THE CHALLENGES AHEAD

T. KIRKWOOD - Institute for Ageing and Health, Campus for Ageing and Vitality, University of Newcastle (Newcastle upon Tyne, United Kingdom)

After a long period when ageing was dismissed as just too complicated for serious scientific study, we now have a very good idea about the underlying reasons for why ageing occurs and how it is caused. Ageing occurs through the gradual, lifelong accumulation of damage that results from the limited capacity for maintenance and repair, which in turn has been strongly shaped through natural selection (the “disposable soma”). Nevertheless, the fact that the enigma of ageing is now ‘solved’ does not mean that the detailed understanding that will be needed to make practical use of its solution is near at hand. The intrinsic complexity of the mechanisms indicated by the solution requires the adoption of systems-biology approaches to the analysis of: (i) how the networks of cellular maintenance are vulnerable to damage, (ii) how these networks are regulated, (iii) how damage plays into the pathogenesis of degenerative diseases, and (iv) where interventions might most successfully be targeted. These challenges will require radical changes in the ways that ageing has been investigated to date.

Reference: Kirkwood TBL. A systematic look at an old problem. Nature 2008; 45:644-647.

SA6 044-4 MAKING SENSE (AND MAKING USE) OF PATTERNS OF MAMMALIAN LONGEVITY

S. AUSTAD - University of Texas, Health Science Center (San Antonio, United States of America)

The new understanding of aging that emerged near the end of the 20th century, combined with advances in understanding evolutionary relationships among species, offers an explanatory framework for certain patterns of aging and longevity among mammals. For instance, large species typically live longer and decay more slowly than small species, although there are numerous exceptions to this pattern. If one corrects for body size and focuses on evolutionary history of mammals, it can be seen that exceptionally slow aging and long healthspan has evolved many times. This repeated evolution of slow aging, such as seen in bats, marsupials, and multiple times in rodents allows us to ask new questions about the evolution of long life, such as whether there are many, few, or even one mechanism by which aging processes can be combated. Focused investigation of the molecular processes embodied by multiple species that have achieved exceptionally long life will yield insight into processes relevant to retarding aging in all species. This talk will discuss several candidate processes that have emerged from initial comparative studies.