Louis Rene Garcia, Texas A & M University
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As worms age their ability to mate and mate quickly decreases. Luis Rene Garcia has been looking at how growing older affects the reproductive fitness of C. elegans, he spoke to Chris Smith about these findings...
L. Rene - The goal-oriented task that we were studying is the ability for this little animal – C. elegans (it’s a nematode) to inseminate its partner. The animals can do this pretty well, but as they start to advance at age, the first thing that goes wrong is their ability to coordinate all the different little sensory and motor steps that they need to do in order to successfully inseminate their mate. There is such a competition for reproduction that the males have to compete against each other. So, their responses have to be really fast and very coordinated. So, if you were to watch these animals as they age, they look pretty well, but the first thing that happens is, if their coordinations go off a little bit, they fail to compete. And so, their reproductive success starts to decline.
Chris - So how did you then take that forward, what were the steps you took to study why they show this progression towards being completely incapable of competing?
L. Rene - We assumed that this is a natural process and the way to get at this, we thought, “Well, let’s find a mutant where the animals can mate very well when they're young” but they degrade at a faster rate than wild type. Once we identified that, we can say, “Well, what are the processes that degrade or is different than those animals and those are probably very similar to what normally degrades in a wild type normal male.”
Chris - So, how did you go about finding the gene, or a gene, which might be linked to this premature ageing phenomenon that you were searching for?
L. Rene - So, we made the hypothesis that overeating will accelerate the decline of the ability of the males to mate. So then we just surveyed from mutations where visually, the males made more fat and the Sir-2 mutant happened to be a mutant that fit that bill. We then analysed the mating behaviour of these mutants and found that when they're very young, they mated just as well behaviourally were like wild type animals. However, they displayed a premature decline in their mating behaviour. And so then that allowed us to hypothesise that in a wild type animal, this gene is what regulates the durability of the circuit as the animal is ageing.
Chris - What does Sir-2 do? How does it work? And how does it influence this ageing process?
L. Rene - Sir-2 is an enzyme that deacetylates proteins and one of the proteins that it deacetylates are histones. These are proteins that globally regulate RNA synthesis in the genome. But this enzyme could deacetylate other proteins. And so, its job is basically to turn up or turn down the activity of proteins. What we found, this protein regulates the genes involved in breaking down molecules to get energy and genes that are involved in taking those breakdown products and then building up new molecules.
Chris - So, what should genes which are concerned with how I get energy out of food be related to how fast – if I'm a worm that is and maybe it’s true for humans as well – why should that be affecting the ageing process?
L. Rene - So, in order for the males to compete with other males, they have to have really fast responses which means that their neurons have to fire very fast and their muscles have to fire and contract very fast. In order for that to happen, the animal has to burn a lot of energy. And so, the animals do have to consume a lot of food. As a by-product of energy consumption, they make this by-product called radicals which can damage the neural circuitry and when it damages the neural circuitry, the neurons fire inappropriately or the muscles contract inappropriately and that messes up their coordination. So, in order to have the fast responses, there's a trade-off. You have to consume more energy, but if you consume more energy then you'll damage the system and then the ability or the length of time that you can have those fast responses decreases. But in the case for the little animals, all they want to do is mate and mate as fast as they can. And so, it’s not so important that they can mate for longer period of times, but they mate faster than their brothers. So, faster response is what is selected for.
Chris - And what is the mutant Sir-2 doing in these animals to make them age faster? Why do they accelerate their ageing?
L. Rene - The reason is they make more enzymes that are involved in breaking down glucose. So, they break down glucose a lot faster than wild type animals. They of course, make more ATP. But they're probably making more ATP than they actually need to mate and so, the by-product of making more ATP is making these radicals that are damaging their neurons and muscles faster.