How does evolution determine how long organisms can live? This issue is of deep concern to humans, as we now live at least twice as long as our prehistoric ancestors and seek not only to extend our life expectancy but to stay healthy for longer.

A team led by Prof. Thomas Flatt of the University of Fribourg has just published the results of a major study on the evolution of longevity, based on the genetic analysis of fruit flies. The study shows that the immune system plays a key role in extending the natural life span of these insects.

A long and careful selection

Fruit flies (Drosophila) share many molecular and genetic mechanisms with vertebrates and humans. As they only live for one or two months and are relatively easy to handle, they are widely used for molecular studies of animals in general. The team used flies that have been painstakingly selected for an increased lifespan by researchers for over 35 years. This represents more than 200 fly generations – in human terms, this would mean continuously selecting the longest-lived families since the times of Ancient Egypt. Such a large number of generations has helped the researchers to start seeing the long-term effects of selection and evolution at the genetic level.

As is the case in humans, the flies’ immune system weakens markedly with age, making them much more vulnerable to infection when they are old and frail. The study that has just been published shows that in long-lived Drosophila, this deterioration of the immune system with age is practically eliminated: the flies’ capacity for fighting off infections remains strong throughout their lives, even when they are old.

A stronger immune system for a longer life

“We were quite surprised by these results. At first, we expected long-lived flies to show changes in genes that have previously been found to affect aging, such as those controlling the physiology of insulin” says Thomas Flatt. “Instead, we found a strong involvement of genes involved in immunity. Our study is among the first to demonstrate that the evolutionary path to longer life might involve an improved immune system”.

One might wonder why organisms in the wild have not evolved spontaneously to strengthen their immune systems and live longer. The reason is that activating and maintaining the immune system is very costly in energy, and improved resistance at old age comes at the expense of lower vigour during youth. Indeed, while the long-lived flies are better at fighting infections, they have a decreased ability to produce offspring when they are young. Thus, in nature, where lifespan is limited by predators, pathogens and other dangers, a "live fast, die young" strategy is typically favoured.

Does this research have an impact on humans? "It is too early to tell, but it is interesting to note that people who live exceptionally long lives (over 100 years) have an improved immune system and suffer less from chronic inflammation than elderly people who do not live as long" says Thomas Flatt. "I would not be surprised at all if similar mechanisms were found to be at play in both flies and humans”.

The paper’s shared first authors are Daniel Fabian (Cambridge) and Kathrin Garschall (Bergen), two former PhD students of Prof. Thomas Flatt, who moved to UniFR’s Department of Biology in 2017. The department has had several other successes this year, including the highly regarded ERC Starting grants to Stefano Vanni and Nathalie Stroeymeyt as well as an SNSF PRIMA fellowship to Adria LeBoeuf.

Links:

"Evolution of longevity improves immunity in Drosophila" in Evolution Letters

Q&A with Prof. Thomas Flatt for a more technical discussion (Evolution Letters Blog).