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Did scientists unearth the secret to aging?

by Coffee Table Science

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Even the healthiest and luckiest animal, who’s never had any illness or disease and has never been in a life-threatening situation, dies. Several predictions have been made that could explain this phenomenon. Most explanations revolve around the idea that DNA mutates over time, causing terminal diseases like cancer. This might lead you to think that large animals should die more quickly than small animals since large animals have more cells that can mutate.


While this idea could explain why small dogs tend to outlive large dogs, it doesn’t explain why the trend isn’t always true between different species. For example, mice are far smaller and have far fewer cells than giraffes. It would make sense for mice to be less prone to developing deadly mutations and to live longer as a result. This is clearly not the case, as healthy mice tend to live to around 4 years whereas giraffes can live to be 25.


Why does this happen? And can the typical naked mole-rat, who is very similar in size to the mouse, also live to be around 25 years?


Researchers at the Wellcome Sanger Institute have found that different rates in the somatic mutagenesis of different mammals might be the underlying cause of this phenomenon. This is according to a study published in Nature last month. 


What is somatic mutagenesis?


Somatic mutagenesis occurs when mutations develop in the DNA of living, multicellular organisms.


The mutations can be due to exogenous mutational factors, meaning the cause for the mutation is external to the cell. Exogenous factors include exposure to carcinogens, so think: sun-bathing, smoking, and/or drinking. Mutations can also occur endogenously when mistakes occur during the DNA copying process. Endogenous mutations are random and unavoidable.

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Somatic mutations have been difficult to measure in the past. As a result, only limited studies have been conducted on the somatic mutation rates of humans. According to the study, new developments in technology have allowed scientists to expand the body of research.


For their study, the researchers used a modern technique called “laser microdissection” to collect over 200 samples from the tissues of 16 different mammals. They then conducted whole-genome sequencing on each of the specimens. This allowed them to see the number of times a mutation occurred among the entire strand of DNA. They were also able to get a sense of the mechanisms that caused certain mutations in all the species.


Relation between somatic mutagenesis and lifespan


Several DNA samples were collected from the same animal at a different time in five of the species. These species included the human, the dog, the naked mole-rat, the rat, and the mouse. This allowed the researchers to show that mutations in DNA occur at a constant rate throughout the species’ lifetime. With this new understanding, they could then tell the mutation rate of any animal, given its age and the number of mutations in its DNA.


Researchers then compared these mutation rates to the typical lifespan of each species. They found a good anti-correlation, meaning that a faster mutation rate is a good predictor of a shorter lifespan. They did the same thing for body mass and lifespan and didn’t find as good an anti-correlation.


What does that tell us?


The findings of the study show that mammals with slow mutation rates are likely better off than mammals with fast mutation rates.  This explains how the giraffe can outlive the mouse, which has a much faster mutation rate. It also supports the idea that large animals likely evolved to suppress somatic mutations, allowing them to live longer.


And while at this point, it can’t be said that somatic mutagenesis is the cause of a mammal’s given typical lifespan, it’s likely a contributor. One thing is certain though, according to the authors of the study. Exploring the phenomenon further can help us better understand its effects on aging, disease, and evolution.

The findings of this study were published in Somatic mutation rates scale with lifespan across mammals

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