Longevity Briefs: Transferring Regenerative Genes From One Species To Another

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Some animals have the ability to regenerate whole limbs, organs, or even their entire bodies after being cut into small pieces. By comparison, we humans (and most other mammals) have hardly any regenerative capabilities, leading to the accumulation of permanent damage throughout life. Could this one day be fixed? Can we learn anything from regenerative species that could be applied to slow down human ageing? In this study, researchers investigate what happens when genes responsible for regeneration are transferred to species that lack them.

The discovery:

In the study, researchers used genetic techniques to transfer regenerative genes to fruit flies. Specifically, they gave the flies genes called HRJDs (highly regenerative species-specific JmjC domain-encoding genes). While that might sound like a mouthful, all you really need to know is that these are genes that are common to species with exceptional regenerative abilities, like starfish and hydra, but notably absent from their evolutionary relatives that lack said regenerative ability. The evolutionary ancestors of the fruit fly possessed HRJDs, but these genes were subsequently lost.

Surprisingly, fruit flies expressing HRJDs actually had shorter lifespans and less regenerative capacity in their developing wings than unmodified fruit flies. However, in fruit flies in which HRJDs were only ‘switched on’ after the flies had finished developing into adults, average lifespan was extended. The flies’ guts also underwent changes: they lost regenerative capacity, making them more vulnerable to injury. In return however, the genes enhanced the ability of stem cells in the intestines to develop into the correct cell types, which improved the function of the gut barrier with age. A decline in gut function appears to be the major contributor to death from old age in fruit flies, so this is probably why the flies with HRJDs lived longer.

The implications:

So, why did HRJDs not have the anticipated effect? One possible explanation is that in organisms naturally expressing these genes, they are only activated after an injury has occurred, and then switched off once regeneration is complete. In these experiments, HRJDs were active for at least the duration of adulthood. Another consideration is that there may be other, unidentified genes that are needed to work in tandem with HRJDs. One thing we can take away from these kinds of studies is that harnessing ‘anti-ageing’ genes from other species is not straightforward. Genes have complex interactions with their environment and each other and cannot be relied upon to work the way we expect them to. Studying them may help us learn about the biology of ageing, but it will take a long time to translate this knowledge into anything practical.