Longevity Briefs: What Can The Adorable Axolotl Teach Us About Ageing?

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:

Axolotls are salamanders, well known for their ability to regenerate limbs, eyes, and even parts of their brains. They also live exceptionally long lives for amphibians their size (over a decade on average), and the way in which they age is very unusual. Most complex organisms progressively decline in physical and cognitive function as they grow older, racking up age-related diseases until they eventually succumb to one of them. Axolotls, on the other hand, appear to be members of a rare group of organisms that show essentially no signs of ageing right up until they die. 

This way of ageing is known as negligible senescence, and the way organisms achieve it is of great interest to science. Humanity would benefit enormously from gaining full or partial negligible senescence – imagine enjoying your final decade of life with the same health you had in your 20s.

The discovery:

In this preprint study, researchers attempted to develop something called an epigenetic clock for the axolotl. This is where researchers look at molecular tags called methyl groups that are added to or removed from certain sites within an organism’s DNA in order to control which genes are ‘switched on’. The distribution of these methyl groups changes throughout life as part of a process called epigenetic ageing. With enough data, algorithms can be created that will predict an organism’s age based on these changes. If that prediction is significantly higher or lower than the organism’s actual age, this suggests that it is ageing faster or more slowly than expected. 

However, when researchers compared the methylation patterns in young and old axolotl, they found that the patterns of DNA methylation were essentially indistinguishable – there was no correlation between epigenetic age and chronological age (number of years since birth). The axolotls only appeared to undergo epigenetic ageing over the course of their first 4 years of life, after which no further signs of ageing were detected. 

Since the researchers chose to study methylation sites within the DNA that were shared between axolotls and mammals, they were able to make some comparisons between axolotl and human ageing. They found that very young humans actually had similar methylation patterns to those of young axolotls, mainly in genes associated with development. However, humans continued to acquire negative epigenetic changes such as those associated with cancer, while axolotls did not.

The implications:

Why are axolotls seemingly able  to ‘pause’ epigenetic ageing while we don’t? The answer may be related to their regenerative abilities. When axolotls regenerate their limbs, their cells are also ‘reprogrammed’ in a process that wipes out many epigenetic changes, allowing them to become whatever type of cell they need to be. Researchers have shown that similar reprogramming can be activated in human cells, seemingly erasing signs of ageing in the process, but there are many barriers to actually implementing this in living humans.

If you’d like to learn more about this strategy for reversing ageing, we have an in-depth article, Reprogramming 101, that covers how it’s done and the potential dangers.