June 2007 had just started and San Antonio, Texas, was bathed by a glowing sun and blue skies, with a temperature of approximately 80ºF and high humidity. Possibly not the best environmental conditions to sit through a scientific meeting, but the air conditioning at the venue and the quality of the papers presented made it perfectly tolerable. In fact, it soon became clear that it was preferable to remain in the room listening to the talks than to go outside.
The meeting in question was the American Aging Association's 36th Annual Meeting and 21st Annual Meeting of the American College of Clinical gerontology: Current Directions in Studying Mechanisms of Aging held in San Antonio, Texas on June 1-4 2007.
The meeting was preceded by a symposium, on Therapeutic Intervention in the Aging Process. This session was quite rich in diversity, and the various papers presented focused on wide-ranging strategies to determine potential targets for intervention and the use of various model systems.
Brian Kennedy (Washington University) proposed a grandiose approach to study evolutionary conserved pathways in various model organisms, yeast, worms and mice. These, included genome-wide screens for gene deletions in yeast resulting in extension of replicative or chronologic lifespan, followed by knockdown of target genes by iRNA in C.elegans and finally generation of mouse knock-out models.
Arlan Richardson (University of Texas) reminded us that there may be more to the "free radical theory of aging" than simple, increased oxidative stress affects on lifespan, despite all the correlative evidence present in the literature. He showed the lifespan effect of various knock-out/transgenic mice models affecting the antioxidant system. The results showed that Sod2-/+, Gpx1-/- and Gpx1-/-Sod2-/+ mice have the same lifespan as wild-type mice despite increased sensitivity to oxidative stress and increased oxidative damage. Surprisingly, overexpression of thioredoxin 1 did increase mean lifespan.
Following the role of antioxidant defence on mice lifespan, Gordon Lithgow from the Buck Institute presented his approach to high-throughput screen of compounds with antioxidant properties on C.elegans lifespan, similar approaches were presented by Kerry Kornfeld (Universityof Washington) in the same model organism and Sige Zou (University of Texas) in the Mexican fruit fly Anasthepha ludens.
We also had the opportunity to hear three presentations on the studies conducted by the National Institute on Aging (NIA) Interventions Testing Program (ITP), which aims at testing the effects of different candidate drugs on mice lifespan. One important feature of this study was that the data was being generated independently by three independent laboratories, with genetically heterogeneous mice.
The next day, when the actual meeting began, we were already filled with food for thought from the previous day, but ready for more. Despite the jet lag, (it does take a few days to attenuate its effects), despite the welcome reception which involved alcohol consumption, (it does not work in making you go to sleep and might result in even earlier awaken), the meeting did start at 8am with opening remarks by the meeting organiser Holly van Remmen.
Here are some highlights from the first day:
Andrew Dillin from the Salk Institute, presented his groundbreaking work showing the role of PHA-4 in the regulation of diet-restriction-mediated longevity in C. elegans. John Phillips (University of Guelph) showed evidence in Drosophila for an important role of oxygen metabolism in regulation of fly lifespan. He showed that in normoxic conditions (20% oxygen) SOD1 and SOD2 mutants show early onset of mortality, however, chronic hypoxia is able to suppress this phenotype. This presentation generated discussion on the fact that the effects of antioxidants on lifespan seem to work differently in evolutionarily remote model organisms.
A session on the role of IGF-1 in various mouse models followed. We learnt about the mechanisms mediating extension of lifespan by overexpression of hormone Klotho, which is thought to be due to its ability to inhibit IGF-1 signalling and to reduce oxidative stress, as presented by Makoto Kuro-o (University of Texas). He also presented data suggesting a role of fibroblast growth factor on regulation of lifespan, since mice defective on fibroblast growth factor-23 exhibited similar phenotypes to the Klotho deficient mouse. Interesting was the fact that other mouse models questioned the effects of IGF-1 in regulation of lifespan. In work presented by Christian Sell (Drexel University), IGF-1 hypomorphic female mice revealed a 18% increase in lifespan, but this was exclusive to females, since males showed no different to wild-type mice. Surprisingly, independent work by Martin Adamo (University of Texas), showed that mice deficient in liver IGF-1 showed a slight increase (not statistically significant) in median lifespan in females and a decrease in median lifespan in males. This led to discussion and speculation on the role of hormones testosterone/estrogen composition in modulation of the effects of IGF-1 on lifespan.
Lunch was followed by a debate moderated by Steve Austad on the subject "Is Aging programmed?". The inclusion of such a debate in the meeting proved to be a successful gamble by the organisers, since it led to active participation by the audience and the emergence of interesting questions and discussion. The discussion featured two panellists: Daniel Promislow from the University of Georgia and Valter Longo from the University of Southern California. Daniel Promislow, argued eloquently that aging is not programmed and a non adaptive-process, oblivious to the force of natural selection and supported his arguments with substantial evidence. Valter Longo presented his own data on the model of S. cerevisiae, which he believed supported the existence of a programme of altruistic ageing and death.
One of the highlights of the first day of the meeting was the trans-atlantic awareness and collaboration symposium on aging research. One of the purposes of this session was for the American scientific community working on ageing to be aware of some of the research carried out in the United Kingdom. And if diversity was what was expected, diversity was what was offered. In only one hour and a half, the audience was exposed to such disparate subjects as Werner Syndrome, the effects of aging on the immune system, the circadian clock, age-related changes in a pond snail, age-dependent changes in elastic fibres, mitochondria and ROS generation in fibroblasts and contracting muscle cells.
Sunday opened with a session on nutrient sensing. Jim Jefferson and George Thomas from the universities of Pennsylvania State and Cincinnati respectively, presented data on mTOR signalling and Pere Puigserver, from Washington University on his ground breaking work on PGC-1 a and its regulation by SIRT-1.
David Nicholls from the Buck Institute presented some interesting work on bioenergetics of cultured neurons exposed to pathological concentrations of glutamate. He showed evidence that opposed the model of calcium entering mitochondria being responsible for increased oxidative stress, by showing that glutamate activation of NMDA receptors uses the full respiratory capacity of the in situ mitochondria. He concluded that limited ATP generation capacity could be responsible for excitotoxicity, which is a feature of many age-related neuronal diseases.
Rochelle Buffenstein (City College of New York) presented her quite intriguing work on the naked mole-rat. We learnt how this exceptional longed-lived species defies the belief of a causal role for oxidative stress in the ageing process. Despite their longevity (more than 28.3 years), these rodents showed higher levels of all the markers of oxidative stress when compared to age-matched mice. These results suggested that naked mole-rats aged and died due to other mechanisms apart from oxidative stress.
This very stimulating meeting finished with the attribution of the distinguished Achievement Award to Edward Masoro from the University of Texas, for his vast contributions to the field of ageing.