Leonard Guarente, professor of Biology at MIT, talks about uncovering the gene that also controls how other organisms, and perhaps humans, grow old.
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Leonard Guarente on Anti Aging Genes Question: Can you define the aging process for humans? Aging process – you can describe it statistically in terms of mortality curves, and what that means is that the probability of dying increases with your age. And the reason is that there's a degenerative process that's occurring in cells and tissues that makes you increasingly less robust as you get older, and opens up the doors to diseases of aging, the major diseases – diabetes, Alzheimer's disease, cancer, cardiovascular disease, osteoporosis – and eventually will kill you. So it's a very pervasive process that has many, many things going wrong all at the same time. Question: What have been the key breakthroughs in the last decade in understanding aging? Well, you're talking to somebody who is not unbiased in this area. And you know, I think the sirtuins have really been, to my mind, the completely unexpected new thing to come along. Now, this came from the studies in yeast that I described a few minutes ago, where we were looking for anti-aging genes. And after about nine years of doing this , the first nine years – we started working in this area about 19 years ago – the first nine years were spent in yeast, trying to find the right gene. And we came upon a gene called SIR2. And the SIR2 gene was an anti-aging gene. And what I mean by that is, when you made it more active, the cells lived longer; they divided more times. When you made it less active, they lived less long. So this looked like a really interesting gene, and it was the only gene that we came across that did this. And so we thought it was interesting. Then we carried out a similar kind of study in a different organism that people study in the lab, the roundworm, C. elegans, and again we're looking: are there any genes in the genome of C. elegans that are anti-aging genes? And we got the same gene. We got a gene that had the same sequence, similar sequence, as the yeast SIR2. So that's an amazing finding, because what it means is, if the SIR2 gene is counteracting aging in yeast and in worms that it's doing that universally. And that would include mammals, and it would include us. So it really right away speaks to a universality of this process. So I think that's one thing that's highly significant about this, is that the gene is conserved, and we think its effect on the aging process is conserved. Now, the piece of this that makes it, I think, particularly exciting is, you say, well, okay, there's this gene that makes you live longer if it's more active. Why should that be? What does this gene actually do? Okay? And what we know is, genes, of course, are the blueprint to specify proteins, and the SIR2 genes encode particular proteins. The proteins are called sirtuins, okay? And we were really, really eager to find out what the sirtuins actually did in cells. And just almost exactly 10 years ago, a little bit more than 10 years ago, we discovered it. And they have an enzymatic activity in cells that enables them to modify other proteins in cells. And that can really change the metabolism, the physiology, of a cell and then by extension, of entire tissues and an entire organism. But the critical thing about this activity is that it was completely coupled to this small metabolic molecule in cells called NAD. No NAD, sirtuins are dead, okay? So NAD links sirtuins to diet and metabolism, because diet and metabolism affect the availability of NAD in cells. So we came up with a hypothesis 10 years ago, when we discovered this activity, that sirtuins might really be the link between how diet affects how long you live and how diet affects your predisposition to diseases. And this was a, I think, radical idea. I think there are a lot of people out there still critical, don't believe it. But I think the data is mounting, in mice particularly, that says that this may actually be true. And so the idea would be that on a low-calorie diet, a diet that's been termed calorie restrictio