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Biogerontology Finding the Fountain of Youth



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The Tree of Life, the Philosopher's Stone, the Holy Grail; throughout human history the myth and legend of immortality and extended life has been a common cross cultural theme. Yet one that has always stayed obscured mysterious and decidedly out of reach, that is until now and the advent of genetic Biogerontology. At the University of Southern California, Dr Valter Longo not only looks Death in the eyes daily but they play high stakes poker together. And on the line is nothing else but the extension of human life itself and the good doctor is beginning to win.

A subfield discipline of Gerontology, Biogerontology is the study of the biological processes of aging and how it might be slowed or even halted. At USC Dr. Longo is the Assistant Professor of Gerontology and Biological Sciences and holds the Paul Glenn Chair of Biogerontology. For the past fifteen years Dr Longo has been armed with the belief that aging is a process that can be understood and ultimately treated. A belief that has caused Dr Longo and his team to not only revitalise the Gerontology field that had seen a slump since a nineties boom, but to actually make the first steps towards a true genetic anti-aging process, a real holy grail.

It all started with Genes, Starvation and Yeast, bakers yeast, one of the most scientifically studied organisms. But the thing about this yeast is that it has very similar genes to humans. In particular Dr Longo took a cue from Leonard Guarente at the Massachusetts Institute of Technology who studied the SIR2 (silent information regulator 2) gene in 2000. Shortly after Dr Longo initiated a study into this gene and released a paper in 2005 analysing the gene expression in yeast aging chronologically. But whilst Guarente looked to over express the gene to achieve a slight anti-aging effect, Longo had other ideas.

"We were convinced that SIR2 had the potential to be a more potent pro-aging than an anti-aging gene and the reason was in part because of the similarity with this other gene, called HST1, which negatively regulated so-called protective genes. So we set out to test whether SIR2 could do the opposite of what everybody said it does." - Dr Longo

What Longo discovered was that by removing the SIR2 gene in the yeast he effectively cut of its ability to prevent an extreme survival mode, the very purpose of the SIR2 gene. Now this is where the Starvation or Caloric Restriction (CR) comes into play. Back in the early nineties Roy Walford a pioneer in CR happened to be Longo's professor and Longo also studied the effects of CR at The Biosphere 2 project. So what is CR and why is it so important when combined with the removal of the SIR2 gene?

CR is the specific restriction of calories in an otherwise healthy diet, and when performed leads to some remarkable results. Although CR only came into prominence in the Nineties it started in 1934 with Clive McCay and Mary Crowell at Cornell University. They discovered that by radically reducing calorie intake but still maintaining a healthy diet in lab rats, their lifespan was extended by up to 50%. 43 years later in 1986 Roy Walford and his student Richard Weindruch took up the torch and led studies that proved and extended on the original findings. There are a number of theories as to why CR works, but it has been proven to work in all the species it has been tested on with the exception of the common housefly. One of the theories is where Longo comes back into the picture with the adoption of CR as one of the elements combined with the removal of the SIR2 gene. It is believed with CR that the body enters into an extreme survival mode (ESM) which takes control of the body's processes even that of reproduction. In the ESM state the body speeds up the process of DNA repair and provides increased protection against cell damage. One of the main components of aging is the breakdown or mutation of DNA and increased cell damage, to the point of cancers etc and eventually death. Now the SIR2 is the one responsible for limiting or preventing the ESM state, remove this gene and add CR and you get a whole other card game going on.

"Evolution designed our genes, our army, to be ready for growth and reproduction. We can use our energy to grow and reproduce, or protect ourselves."-Dr Longo

And Dr Longo's and his army have this year 2008 achieved an unprecedented 10-fold increase in the lifespan of their yeasts. A leap forwards in the field, one that greatly surpassed Longo's original expectations.

"We expected a small boost in longevity, but not a 10-fold increase. It's remarkable."- Dr Longo

The normal lifespan for yeast is one week and Longo has pushed this to ten weeks. Not since the dawn of agriculture extended our lifespan, has the possibility to again do so ever been closer. We stand at a threshold that could indeed lead to new age of longevity and once again change us forever.

"We're setting the foundation for reprogramming healthy life." -Dr Longo

From this profound achievement never one to rest on his laurels Longo and his army is extending along two lines. One to further the SIR2 and CR research into mice and beyond, and the other all the way to Ecuador where there lives an extraordinary group of people. In this select group Longo has found two mutation genes that are correspondent to genes in yeast.

"People with two copies of the mutations have very small stature and other defects. We are now identifying the relatives with only one copy of the mutation, who are apparently normal. We hope that they will show a reduced incidence of diseases and an extended life span." -Dr Longo

Because while this group had these mutations they were for the most part cancer free, as a direct result Longo believes from the same genetic mutations as the yeast.

"age-dependent mutations increase at a much slower pace in organisms lacking RAS2 or SCH9 and at a remarkably low pace in organisms lacking both SCH9 and SIR2, raising the possibility that the mutations that cause human cancers can be delayed or prevented. Notably, mutations that increase the activity of human homologs (genes descended from a common ancestral DNA sequence) of the yeast SCH9 and RAS2 genes play central roles in many human cancers...What if we could achieve a balance by switching those genes off when we want to? Twenty or thirty years from now, we might have the ability to reduce the activity of genes. In the long run, I think that balance may not be too hard to achieve." -Dr Longo

As our understanding of DNA grows it is scientists like Longo who are paving the way towards a future of limitless possibilities. A future that, should we survive wrecking our own planet and putting it back on track, could lead us ever outwards into the larger universe. Perhaps in lieu of faster than light travel being able to live longer may see us able to travel to new worlds in lifetimes, as opposed to generations that would be currently required reaching just outside our own solar system. Space colonisation aside, the ability to live even fifty percent longer say to 160 or so, is coming upon us and with it a radical change to our minds, societies and world. Indeed with the current rate of scientific discovery and implementation the babies of today should be the first recipients of such an advance in life extension.

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