Premium Beauty News - Your research work has recently led your team to findings on the aging of organisms. What about it?
Hugo Aguilaniu [1] - With my team, we explore the genes that affect aging by increasing it or decreasing it but also those that improve its quality. For our work we use nematode worms, a model organism for us, geneticists because it is capable of self-fertilizing and reproducing very rapidly. Its life expectancy is short, 2 to 3 weeks, it has a genome which is 40% equivalent to that of humans.
Our daily work consists in searching, understanding, acting on genes that have the power to regulate longevity. This is hard and tedious work because we are confronted to a lot of information. There are between 16,000 and 20,000 genes in the nematode and fifty of them were characterized as having the power to regulate longevity. These are the ones we are studying. To increase longevity, all the cells need to work better and for this we are looking for "orchestrators"’ of genes, capable of inducing the expression of many other genes. One of the keys to success is a combination of intuition and reasoning.
In 2011, we published [2] results on one of the longevity genes the NHR-80. We highlighted that this over-expressed gene led to a life expectancy 2.5 times greater than that of normal nematodes. Furthermore, some old animals carrying an active version of this mutated gene appear rejuvenated. Relationships with lipid metabolism have been made since the NHR-80 gene governs a cascade of reactions leading to the modification of the expression of several genes including the fat-6, which encodes an enzyme that converts stearic acid into oleic acid. We are continuing our investigations on this subject and are trying to understand how this longevity occurs.
Moreover, in 2010, we published some research work on rejuvenation in the journal Aging Cell [3]. We demonstrated that when fertilization takes place the amount of damaged proteins present in the oocyte decreases sharply. We have put that in connection with the proteasome (an enzyme complex responsible for the targeted degradation of proteins). It is a rejuvenation process that prevents the transmission to the offspring of aged components coming from sex cells.
We study mainly the impact of reproduction on longevity as well as the effect of caloric restriction on aging. How do they act on longevity? which genes are involved? can they be handled without reducing the caloric intake for example, what ways can be found to mimic the benefits without having the drawbacks?
Along these lines of work, we also focus on the role of epigenetic changes on aging. What is the impact of these changes in the structure of the genome? We are no longer working on genes but on how the DNA is folded into the cell. These are basic research issues but with numerous potential applications.
Premium Beauty News - Can the work conducted by your team and yourself on nematode worms have a direct impact in the industry an particularly in cosmetics, which has long been looking for eternal youth?
Hugo Aguilaniu - All the genes on which we are focusing in the nematode worm have direct cousins in humans. A gene is a sequence of several thousand base pairs and the ones we are studying have up to 90-99% homology with humans.
The cosmetic industry, who could use some activators of longevity genes in its products, is therefore paying a close attention in our findings. We are also in touch with some private stakeholders in this field. It is fairly easy to find molecules that mimic the mutation that was found, and to undertake measurement tests on human cells like keratinocytes.
As for the pharmaceutical domain, gateways are narrower, there is still a long way to go because we are very far from the drug and we do not know yet how to perform transgenesis in humans. Our findings are regarded by the pharmaceutical industries as pipelines, main lines of research. However, genes that were found in nematodes were also found in mice and Drosophila.
One of the solutions would be to have a drug that would act on the quality of aging instead of longevity. This is a major focus for the years to come, knowing that in 45 years life expectancy has increased by three months each year. Besides which, the issue on aging is, beyond the scientific challenge, a huge social issue.
Premium Beauty News - Other teams are working on longevity, a subject whose challenge we understand is important. Are there possible collaborations?
Hugo Aguilaniu - We are following of course what is done in this area. There are in France, two or three teams like ours working on the genetics of aging, we have some contacts in the United States, England, Germany. We study a book that fills every day a little more and we all contribute to add some pages to it. We can take inspiration from the mechanisms discovered by our colleagues even if the studied organisms are very different. Some complementary activities exist between laboratories. A large quantity of articles is published every day. In our laboratory, we have an average of one publication a year and currently we have five under investigation.
