The first fantasy: In the Hollywood movie, late at night in her lab the young attractive researcher discovers how to activate “The Longevity Gene,” making human life spans of 200 years possible. Then her “secret” gets stolen by bad guys and she sets out to get it back. And the story goes on from there. In real life the scientific situation is nowhere so simple. There are hundreds of genes that have something or the other to do with longevity and dozens of complex proteomic signaling pathways that weave them and other genes together. There is no single known master longevity gene, and in fact such a gene might not exist. So, what is known about “longevity genes?” A couple of recent studies provides clues:
For one thing, there appears to be a remarkable similarity of “longevity” genes across a wide spectrum of species ranging from yeast to worms to flies to humans. That appears to be a conclusion revealed by a proteomics study done by the Buck Institute for Age Research based on a “longevity protein network” developed at Prolexys Pharmaceuticals in Salt Lake City, UT. The longevity network looks at 3,271 interactions among 2,338 proteins that impact on life span in yeast, nematode worms or flies. It also looks at equivalent human versions of 175 of these proteins and 2,163 additional human proteins that interact with those proteins. The longevity protein network was derived from the Prolexys human interactome database which contains over 120,000 non-redundant interactions among human proteins – the largest of its kind in the world.
“Researchers found that there is a complex web of interactions among the human equivalents of the many longevity genes found in simple animals. The results revealed a ‘surprisingly close relationship between aging processes in humans and simpler organisms.’” This is an interesting result given the dramatically different life spans involved and the fact that every species has its own typical life span. Fruit flies, drosophila melanogaster, normally live 7-8 days. Humans normally live 3,600 times as long. It appears that many genes regulating aging have been conserved during the process of evolution over more than a billion years. That result is confirmed by another study done at the University of Wisconsin that identified 25 longevity genes shared by single-celled budding yeast and the roundworm C. elegans.
I believe the result lends credence to the Programmed genetic changes theory of aging. Every species has its own program. And the program evolves as the species evolves. But where is the program? It may not be in the genes themselves but in large part in the epigenome, in inherited patterns of DNA methylation and histone acetylation. We may not be able to change our human genes so easily, but we can certainly affect the epigenome and do so unwittingly every day. So here is a more sophisticated fantasy: we figure out ways to modify our epigenome so we can live longer. For example, suppose we wanted to control P53 apoptotic overactivity leading to cell death or senescence. Suppose we could find a way for reducing activation of P53, say by activating SIRT1 by resveratrol which in turn deacetylates P53. Not completely a fantasy(ref), perhaps this is a minor update patch to the epigenomic longevity program, one that might prove to be of practical value.