Who wants to live for ever?

No one’s ever going to find the Holy Grail. But Swiss researchers are searching for the ingredients of longer life – and they’re looking for them in the genes of flies and ants. By Simon Koechlin

(From "Horizons" no. 105, June 2015)​"Everyone would like to have a long life, but no one wants to grow old”, wrote the Irish writer Jonathan Swift back in 1700. Nothing has changed since then. To be sure, people today live longer than ever before, thanks especially to improvements in nutrition and hygiene and to our immense progress in medicine and healthcare provision. But we still all grow old. As the years go by, the general condition of the body deteriorates. Our susceptibility to illness increases and with it the risk of dying too.

But why? Evolution has brought forth an extremely complex, regulated process of development that takes us from the fertilised egg to the finished individual. Once a body is fully developed, why shouldn’t it be possible for natural selection to keep it in a youthful state into old age – or even for ever? Why aren’t organisms immortal?

“These questions were already being asked in ancient times”, says the biologist Thomas Flatt from the University of Lausanne, who is researching into the evolution of ageing. The Roman poet and philosopher Lucretius, for example, assumed that death serves to make space for new generations. This view was only superseded in the mid-20th century when the modern evolutionary theory of ageing was developed.

Survival of the oldest

The theory explains the evolution of ageing in terms of the natural selection of individuals, not in terms of advantages for the species. It assumes that life is ‘life-threatening’ in the truest sense of the expression. In nature, sooner or later almost all individual creatures become victims of predators, competitors, pathogens or accidents. This means that natural selection hardly continues to play a role in old age.

Let us suppose that a human being has two deadly mutations in his or her genetic material, of which the first will lead to death after 20 years, the second only after 90 years. Selection means that the first mutation will quickly disappear from the population because those who carry it will hardly have any children. The second mutation, on the other hand, has no impact on how many offspring a human being might have in life. “For this reason, mutations can accumulate in the genome over the course of the generations – mutations that will only cause damage late in life”, says Flatt. If living conditions improve (such as better nutrition, for example) and individuals live longer, then this long-term genetic damage can manifest itself, and health will decline in old age.

According to Flatt, this means that ageing is ultimately unavoidable. In fact, experiments and mathematical models all indicate that ageing even occurs in bacteria
and other single-cell organisms that were long thought to be immortal. Nevertheless, says Flatt, there are still many unanswered questions, and he himself is investigating several of them. Using the fruit fly Drosophila melanogaster as an example, Flatt is trying to find out what genes and what physiological mechanisms contribute to certain individuals living longer than others.

Limited immune system

Flatt’s research includes looking into the function and activity of genes in flies. The most long-lived have been bred over a period of more than 30 years. On average they live for 70 days compared to the 45 days that are the norm for laboratory flies. “We found a strikingly large number of differences in the genes responsible for the immune system”, says Flatt. He doesn’t yet know just what impact these differences have on the life span of the flies. But it’s interesting, he notes, that the short-lived flies increase their immune response as they grew old, and this can lead to chronic inflammation. Long-lived flies, on the other hand, seem initially to have a more active immune system, but they reduce it in old age.

It’s not just the immune system that influences life span – the reproductive process does so too. Every individual has only a limited amount of energy available. Using up lots of it for reproductive purposes deprives the organism of the energy needed to survive. Researchers have been able to demonstrate this clearly among fruit flies. If one selects fruit flies for their ability to reproduce very late in life, then their life span doubles after a few generations. “But on the other hand, these flies have problems if they’re supposed to produce offspring early in life”, says Flatt. “They can invest their energy either in reproduction or in their survival functions, but not in both”. This ‘trade-off’ principle, as the experts call it, is ubiquitous. One extreme example is that of the Pacific salmon, which is so exhausted after spawning that it then dies.

However, there are exceptions that give the researchers serious headaches. The queens of several social insects don’t just continually produce eggs: they also live much longer than non-social insects. The garden ant (Lasius niger), for example, which is widespread in Switzerland, has queens that can reach 30 years in age – that’s 500 times longer than the average, says Laurent Keller, an ant specialist at the University of Lausanne. No one knows how queen ants manage to do this. In order to find out, Keller’s group is currently investigating the gene activity of queens of different ages.

The price of anti-ageing

However, it would be a bit extreme to hope that the genetic material of an ant might offer up the source of eternal youth. Because for one thing, the queen ant profits from a very special form of protection: the ant state erects a veritable fortress in which she is guarded from enemies and other outside influences. And better protection means longer life – that’s proven by studies of various animal species. “Poisonous snakes live longer than non-poisonous ones; turtles with a shell live longer than those without one; and birds that can fly live longer than flightless birds”, says Thomas Flatt.

Furthermore, there are many indications that there are always costs involved in living longer – even if they’re not immediately obvious. A good example, says Flatt, is a mutation in the roundworm Caenorhabditis elegans. Worms with this particular gene variation live for a very long time and have no problems with fertility. But when researchers forced these mutants to grow up in competition with wild worms, they lost the battle for survival every time and died out. “We still don’t know why to this day”, says Flatt. “But this mutation obviously has some disadvantage too”.

Simon Koechlin is a science journalist and the Editor in Chief of the magazine Tierwelt.