Introduction

Abstract

Animal models of aging are now a well-established tool for investigating rate-limiting steps in the aging process. Many single gene mutants have been identified in Caenorhabditis elegans, Saccharomyces cerevisiae, Drosophila melanogaster and mice that extend lifespan. By definition, the genetic extension of lifespan implicates these genes in processes that limit lifespan in these organisms. The almost routine identification of such ‘gerontogenes’ has prompted a number of laboratories to search for pharmacological interventions that mimic the effects of manipulating these genetic pathways. These efforts have also been mirrored in the biotech industry, where a number of academic investigators successful in identifying genes that modulate aging have formed companies which aim to produce compounds which extend lifespan, mimicking the effects of ‘gerontogenes’. Hence there is tremendous excitement within the field that insights gained from the genetics of aging in model organisms will ultimately result in the identification of drugs that modulate aging in humans. Insights into mechanisms conserved between species have been gleaned for a number of the gerontogenes identified to date, lending additional credence to the idea that compounds that work in lower order species will have some success in modulating aging in mammals. We therefore convened a meeting to discuss this convergence of ideas entitled ‘Pharmacology of lifespan extension’. Although this is a somewhat bold title (as routine pharmacological extension of lifespan in multiple species is not yet commonplace), we felt the time was right to exchange ideas in an open and constructive fashion and discuss and integrate the approaches for identifying putative agents that modulate aging. On 6–8 October 2005, we brought together investigators from diverse backgrounds such as high throughput drug screening, caloric restriction, stress, and various model systems in which it is trivial to extend lifespan, to facilitate new ideas and discussions with regards to pharmacological interventions in aging itself. It was clear at the meeting that a convergence of approaches was occurring crossing multiple disciplines, focusing on the extension of lifespan via pharmacological interdiction. This was an exciting meeting, and many who attended felt it could herald the birth of a new field. Much remains to be done, however, not least the dissection of mechanistic nuances of how extension of lifespan occurs in model systems, which hopefully will illuminate potential targets for drug design in the extension of lifespan. In addition, there is a vast gulf between the current approaches to identifying life-extending compounds and true high throughput screening technology for drug discovery. What follows is a collection of articles from presenters at the meeting, focusing on approach, regulatory hurdles to be overcome in the introduction of such lifespan-extending agents, as well as potential targets for drugs in both diseases associated with aging, and aging itself. The organizers would like to thank the following for financial support for the meeting: the National Institutes of Health, the Ellison Medical Foundation, Blackwell Publishing, and the Larry L. Hillblom Foundation.