Focus is probably the problem facing every scientist who is ever “lucky” enough to organise a meeting. This problem becomes particularly acute when the subject is ageing and the meeting only lasts one day. Spread the speakers too thin across the topics and most of the audience will be interested for an hour. They will then spend the remaining time doodling cruel caricatures of the speakers, scribbling down half baked ideas that they hope to turn into fundable grants and offering stupefyingly misinformed comments on subjects they really didn’t understand as undergraduates (yours truly has scribbled and stupefied with the best of them). The alternative approach, of tight focus, is also not without its problems. Five of the audience will listen, enraptured, for the day; their pleasure only broken by the gentle snoring of the rest of the scientific community for whom the meeting proceedings are about as worthwhile as an update on the perf o rmance of the Tiblisi women’s second eleven.
It follows that, try as one might, every single ageing meeting is something of a curate’s egg. Mechanisms of ageing & longevity (an Anatomical Society Symposium with additional support from AgeNet, Research Into Ageing and the BBSRC) was no exception. Like the curate I will concentrate on a couple of the areas of this particular egg which I found excellent. Suffice it to say there were also
parts of it I wouldn’t have personally missed if they had stayed in the hen.
I have to confess a personal prejudice in favour of simple model systems and theories with strong testable hypotheses. The opening session, Genetics & Longevity, provided both. Gordon Lithgow (Manchester) gave a workmanlike treatment of mutations which extend lifespan in C.elegans. The majority of the mutants characterised so far (i) upregulate the ability of worms to resist stress and (ii) form part of the daf16-forkhead pathway [1]. The Lithgow lab has recently come up with the idea of using the cosegregation of the stress resistance phenotype and long-life to hunt out new age-style mutants (increased theromotolerance or ITT mutants ). This approach involves mutagenising unsuspecting worms and then subjecting their progeny to a severe thermal shock. This “shake and bake” approach to the genetics of ageing has met with considerable success and is a rather neat piece of lateral thinking. The most interesting observation from my perspective was the presentation of data showing greatly increased lifespans in populations of C.elegans exposed to the catalytic antioxidants Euk-8 and Euk-134. This has to rate as the best news in gerontology since telomerase.
That lifespans vary substantially across the animal kingdom is something every gerontologist picks up fairly early in his or her career. David Gems (UCL) pointed out that there is a 600 fold variation in lifespan just within the phylum Nematoda (lifespans of 8 days to 14 years). David suggested that rather than expressing a single genetic pattern throughout adulthood, the possibility exists for nematodes to express a series of developmental genetic “identities” as they age (a bit like playing a series of tracks from a CD). This concept is developed in some detail in a new ageing hypothesis. David’s tripartite theory of ageing links together evolution, oxidative damage and non-adaptive programmed ageing. Right or wrong the theory leads to testable predictions that are borne out by work with nematode lifespan mutants [2]. As a light aside I was interested to learn that Hydra vulgaris apparently shows negligible senescence [3]. David pointed out that this was in line with his theory, which predicted that organismal senescence should not occur in species where all the cells in the body are turned over. A personal question for me is whether hydra shows a true germline/soma distinction. Answers to the Editor on a postcard please.
Cell turnover is at the heart of the cell hypothesis of ageing. The idea that the senescence (replicative failure) of those classes of somatic cells which divide during life may contribute to whole body ageing. Jose Remacle (Belgium) showed that repeated sublethal oxidative stress can accelerate the onset of senescence in human fibroblasts (measured using a range of markers including telomere shortening). This work supports other observations which show that telomeres are susceptible to oxidative damage and links a major form of exogenous damage with an internal, programmed, counter [4,5]. In vivo veritas? We shall have to wait and see.
A presentation by Emil Toescu (Brimingham) updated the calcium hypothesis of neuronal ageing (essentially the suggestion that small shifts in cellular calcium over long periods of time are functionally equivalent to large neurotoxic shifts in exprescalcium over short periods of time). Emil pointed out that there are a couple of problems with the theory as it currently stands of which the most important is the observation that there does not appear to be any significant evidence of neuronal cell death in the normal ageing brain. That having been said the cytotoxic role of calcium should not be discounted. Normal aged neurones show elongated calcium signals which may act to remove the most active neuronal synapses and contribute to the decrease in connectivity seen in normal brain ageing [6]. The normal neurobiology of ageing is obviously an area to watch and much of the meeting dealt with various aspects of the molecular signalling pathways involved. Local organiser Tim Cohen is to be praised for his networking skills in putting together a meeting of this quality and thanked in advance for his article on the daf16-forkhead pathway which will appear in the next issue of Lifespan.
