58 Australasian Journal on Ageing, Vol 25 No 2 June 2006, 58 –62 © 2006 COTA National Seniors Partnership DOI: 10.1111/j.1741-6612.2006.00150.x Blackwell Publishing Asia Review Article Advances in lifespan extension Strong and weak lifespan extension: what is most feasible and likely? Jayne C Lucke and Wayne Hall Office of Public Policy and Ethics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia Abstract Recent advances in biomedical science indicate that it may eventually be possible to intervene in the biological process of human ageing. This paper overviews the current state of the science of lifespan extension and promising future directions. It is uncertain whether ‘strong’ lifespan extension – the extension of human life beyond the maximum 122 years so far observed – will become a reality. It is more likely that cumulative effects of numerous scientific and biomedical advances in the treatment of common disease will produce ‘weak’ lifespan extension – the extension of average life expectancy. The practical application of molecular, genetic and nanomaterials research may also lead to advances in life expectancy. It is not too early to begin to consider the policy implications of either form of lifespan extension. Key words: age-related diseases, anti-ageing, lifespan extension, regenerative medicine. Introduction The substantial extension of the human lifespan is one of the most challenging promises of the biotechnology revolution. While the means of extending human lifespan by artificial means is not yet known, an increasing understanding of molecular genetics and biological processes of ageing brings closer the possibility of significantly extending life expectancy. Medical advances over the past decades have contributed to an increase in life expectancy in the developed world, and developments in regenerative medicine promise further advances in trauma repair, disease prevention and treatment. Average human life expectancy has increased throughout the 20th century because of reductions in infant mortality and advances in the treatment of chronic diseases of older age [1]. Extrapolation models have been used to suggest that human life expectancy will continue to rise at the same rate [2], with suggestions that the figure for US females could reach 101.5 years by 2070 [3]. However, critics argue that such extrapolations do not take into account the reasons for the observed increases in life expectancy or possible limits on the maximum lifespan imposed by human reproductive biology [4]. This paper examines the current state of the science of lifespan extension and promising directions for two broad types of life- span extension as distinguished by Moody [5]: ‘strong lifespan extension’ in which scientific advances increase both average and maximum lifespan, for example, enabling most people to live to be 112 years and some to 140 years; and ‘weak lifespan extension’, which is the incremental increase in average life expectancy resulting from continued improvements in the prevention and treatment of disease. ‘Strong’ and ‘weak’ lifespan extension may overlap, but the distinction provides a useful framework for discussion. Possibilities for strong human lifespan extension Scientific developments based on diverse models of ageing have led to success in extending lifespan in model organisms and may lead to interventions that will slow the biological process of ageing in humans [6,7]. Among the most promising possibilities for interventions to slow human ageing are the role of the enzyme telomerase in modifying the process of cell ageing [6,8], sub- stances that may mimic the effects of caloric restriction [9] and potential gene targets for pharmaceutical therapies [10]. Developments addressing functional crisis theories of ageing Telomerase Telomeres are specialised structures at the ends of chromo- somes that prevent them from unravelling. Telomeres shorten with every replication of DNA and when they become too short to function, replication stops. One direction for research is to immortalise cells by avoiding telomere shortening via telomerase, the enzyme controlling telomere length. Understanding the key role that telomere shortening plays in human ageing and death may lead to anti-ageing interventions [6]. Oxidative and mitochondrial theories of ageing Mitochondria, the generator of the cell, produce free radicals that result in oxidative stress that contributes to cell ageing [7]. The efficacy of antioxidants in protecting against cell damage and extending lifespan has been demonstrated in model organisms but it has been difficult to extend lifespan in higher organisms [6]. Some remain sceptical about the role of oxidative stress in ageing and the benefit of antioxidants in preventing cell ageing [11]. Nevertheless, many people take antioxidants and believe in their health-maintenance and life- extending potential, and there have been calls for further research on the potential benefits of antioxidant therapy in maintaining cellular health, and extending lifespan [7]. Caloric restriction Restricting calorie intake is the only strategy that has been shown to result in longer lifespan in different species. The Correspondence to: Dr Jayne C Lucke, Senior Research Officer, Office of Public Policy and Ethics, Institute for Molecular Bioscience, The University of Queensland. Email: j.lucke@uq.edu.au