Does genetics determine our life span?

Research in the worm is looking for answers - an interview with Thomas E. Johnson

Thomas E. Johnson studied Life Science at the Massachusetts Institute of Technology and received his PhD in Genetics at the University of Washington. Now he is Professor of Behavioral Genetics at the University of Colorado. Together with his team he is studying aging using the mouse and the nematode worm Caenorhabditis elegans as models.

In the course of the Joint annual Meeting of the ÖGBM, ÖGGGT, ÖGBT and ANGT in Salzburg in September 2006 Thomas E. Johnson was interviewed by dialog<>gentechnik. 

Prof. Thomas E. Johnson:
I chose C.elegans about 25 years ago, because it has a lot of characteristics that make it easy to do experiments. In humans, aging is a phenomenon that takes 70 years or even longer to observe. It is one of the primary characteristics of C. elegans, that it has a real short life span. In just two or at most three weeks we can see it go through the whole aging process. So it is a relatively quick thing to study.

Univ. Doz. Dr. Elisabeth Waigmann (dialog<>gentechnik):
Looking at your study system, what would you consider to be the most important factors for aging that you came across?

Prof. Thomas E. Johnson:
The most surprising observation that we have made is, that we can find single genes, whose elimination results in a really dramatic life extension. We now know that there are many genes like that. We have identified as many as 200 genes on the nematode. When we eliminate those genes, and by eliminating I mean, that we introduce a genetic mutation, the elimination of these genes function results in a longer than normal life span. This is really kind of counter intuitive. First that kicking out a single gene can result in eliminating a lot of the diseases that would normally occur in these animal and second that we can get such a dramatic effect as to almost double and in some cases more than double the individual’s life span.

Univ. Doz. Dr. Elisabeth Waigmann (dialog<>gentechnik):
If the elimination of those genes prolongs the life span, why does C. elegans keep these genes?

Prof. Thomas E. Johnson:
The reason that the nematode has these genes is that they have a biological function, that is beneficial for the worm, but that has nothing to do with aging. A very clear example is the genes that I have studied the most, for instance, a gene that is called age1 and other genes that are in that pathway.

When I use the term pathway, I mean to say that the proteins that are encoded by genes directly interact with each other, one sort of piggy-backing on to the one after it.

This age1 pathway that we identified clearly has as one of its primary targets, something that we call a transcription factor. Transcription factors are proteins that are involved in the regulation of many other genes. For example, the transcription factor that I have just been talking about probably regulates as many as 2000 and maybe as many as 5000 genes in the nematode genome. So when that particular pathway is modulated, it not only expands life span, it results in the changes of these thousand of other genes functions and many of these changes are not optimal.

Age1 is needed to optimize the organism’s fitness. I use fitness here to mean an evolutionary concept of fitness, so that the nematode can best fit into its soil environment and can reproduce - this gene is not really needed to cause aging. So that the aging process, we now are pretty sure, has not really been selected for at all. It is a passenger of the rest of the evolutionary program.

Univ. Doz. Dr. Elisabeth Waigmann (dialog<>gentechnik):
And beside those genetic factors, are there any other factors, which would influence the life span?

Prof. Thomas E. Johnson:
We have spent a great deal of time looking at other factors in addition to the genes. After all, most of us are stuck with the genes that we have. It is very tough to do much about that. Sometimes when people ask me, what they can do to allow themselves to age slowly, I tell them that the most important thing is, to choose long lived parents. It is clear that if your parents are long-lived, you have a certain predisposition- maybe as much as a four fold higher probability of living long.

But there are also environmental things that we can do. And in the nematode we can test these environmental interventions very cleanly. For example we can change the food source, we can limit the amount of food that the nematode eats and we can expose them to drugs. And all these interventions can have a beneficial effect. For instance there are now as many as a dozen drugs tested in the nematode shown to prolong life span. In several instances, these interventions really dramatically prolong the live span, up to two fold, and make the worm healthier as they live longer as well.

Univ. Doz. Dr. Elisabeth Waigmann (dialog<>gentechnik):
Experiments show that even if you have genetically identical worms and you keep them under the same conditions, they still have a difference in life span. How do you explain that?

Prof. Thomas E. Johnson:
You can think of these nematodes as being identical twins, except that with nematodes we are not limited in the number of identical twins we can make. In some of our studies we have actually studied as many as 60 thousand genetically identical twins, all aging in a constant environment. If there is nothing but genes and the environment that are causing these individual’s life spans, they should all die at the same second. And we don’t see that, we see them dying with a huge range of individual life spans, ranging from the first day of adult life (the day that we started looking for death) up to as long as two to three months of age.

We call that stochastic or chance variation. The reason that chance variation is so important in aging and the determination of individual life span is that you can only die once, then it is all over and there is no chance to rise from the death. That is a really profound observation that unlike a disease, an illness or an injury to the body, death cannot be treated or cured. Even though we don’t know what causes them to die, they really only have one chance. At the first critical event where they fail to stay within the range of viability, we see death occur.

We can actually predict for an individual nematode, how robust it is and how likely for one of these events it is to occur. We can predict this several weeks in advance, which in human terms is like predicting a hundred years in advance, that one individual of an identical twin pair is going to be more robust than the other individual. At the age of twelve we might be able to say that this is going to be the long lived twin and the sibling is going to be short-lived. And this has profound implications for the human condition.

Univ. Doz. Dr. Elisabeth Waigmann (dialog<>gentechnik):You already switched to humans now. Based on these C. elegans experiments, how much can actually be translated to humans, since they are so different in their life span? There might be a big chance that the mechanisms are also different.

Prof. Thomas E. Johnson:
I think that is absolutely right. We have to be very careful and even sceptical of whether or not, some of the observations that we have made in the nematode have much relevancy or even any relevancy for the human. After all we are five orders of magnitude bigger and certainly a couple of orders of magnitude more complex. We have a life span that is years, as supposed to the few weeks that a nematode lives. So I am very careful to say, that anything that we learn in the nematode has an immediate application to the human.

It is actually surprising to me, that there is increasing evidence, that one of the genes that we have identified in nematodes does have some relevancy in determining human life span. But after all, six hundred million years ago the last common ancestors of the nematodes and of the humans lived in some primitive environment and had identical genes. Generally, genes have evolved differently between the humans and the nematode. However, it is not impossible that genes, which have determined aging at that time, still determine aging now. Even though, as I pointed out, evolution does not care about aging. If the aging process has been conserved over that time period, then similar aging genes could be found in nematodes and in humans.

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Erstelldatum : 13. Okt. 2006 13:54
Letzte Änderung : 17. Okt. 2006 13:35
Gedruckt am : 9. Feb. 2010 11:22