▎ WuXi AppTec content team editor
Animal species in nature are rich and diverse, each with its own characteristics, and some animals are known for their long lifespans. For example, naked mole rats. The size is similar to our common mouse, its appearance is not impressive, but the naked mole rat is more than ten times the lifespan of mice. There is a "law" in the animal kingdom: often the larger the species, the longer the lifespan. But an outlier like a naked mole rat breaks this pattern. The adult individuals of naked mole rats are only one in 23,000 giraffes, but they can all live for more than twenty years!
Why do some animals live longer than others? In the latest issue of the journal Nature, scientists have provided clues to this enduring problem by measuring somatic mutations in animals.
Cells in the body are constantly undergoing genetic mutations, and it is estimated that human cells receive an average of 15 to 40 mutations per year. While most are harmless, there are always some mutations that could put the cells on the path of cancer. As we age, accumulating somatic mutations may drive the development of cancer and are also considered an important cause of aging and other diseases.
From the perspective of somatic mutations, longer lifespans and larger body sizes (more cells) mean that more cancer risks may accumulate. But in a study recently published in the journal Nature, scientists examined nearly 200 species of mammals of varying lifespans and sizes, specifically comparing their risk of cancer death, showing that those species with longer life expectancy and larger sizes are not more likely to die of cancer.
In other words, large, long-lived mammalian species are likely to have acquired some more effective cancer defense mechanisms over the course of their evolution. This hypothesis is very heartwarming because it means it is possible to find some natural anti-cancer secrets from other animals and develop anti-cancer therapies.
▲ Longevity star naked mole (Image: Uploaded by Jedimentat44 on flickr. / CC BY https://creativecommons.org/licenses/by/2.0）
In this new study, scientists add important evidence to this hypothesis. For the first time, researchers at the Wellcome Sanger Institute in the United Kingdom have conducted a comparative analysis of more than a dozen mammals with different lifespans and body sizes from the perspective of the accumulation of somatic mutations with age.
The animals analyzed this time include human, mouse, dog, giraffe, horse, tiger, dolphin, ring-tailed lemur, etc., and of course, the "longevity star" naked mole rat, a total of 16 species. The researchers collected samples from 48 individuals to uniformly obtain epithelial cells from colonic crypt tissue for single-cell sequencing analysis. Genome-wide data from these cells can be well used to estimate the number of mutations a single cell will have each year, which is the mutation rate of that species.
The number of somatic mutations in 16 mammals and the burden of mutations that accumulate with age (partially shown) (Image source: Reference[1])
The results of genome sequencing analysis showed that the rate at which somatic cells in different animals produce genetic mutations is not the same, and the most relevant influencing factor is animal lifespan. Animals with longer lifespans acquire very few mutations each year, and the mutation rate of cells is much slower. In contrast, shorter-lived animals produce many mutations each year, such as mice producing about 17 times more somatic mutations per year than humans.
Interestingly, when animals of different species reach the limit of their lifespan, the total number of mutations per cell is roughly similar. Dr Alex Cagan, lead author of the research paper, said: "We were surprised to find that very different animals like mice and tigers also have similar patterns of genetic change. ”
An important finding of this study was that the amount of somatic mutations that ended up accumulating in species of different lifespans was similar (Image source: Reference[2])
The researchers analyzed that longer-lived animals develop mutations at a relatively slow rate, which may be used to explain why the risk of cancer in long-lived animals does not increase with longevity.
In addition to examining lifespan, the study authors also looked at factors in animal body size, but found no significant association between body size and somatic mutation rates. Still looking at giraffes and naked mole rats, these two have similar lifespans and vastly different body sizes, and the somatic mutation rates are also similar. Compared with mice of similar size, the somatic mutation rate of naked mole rats is unusually low.
▲Animal lifespan is inversely proportional to somatic mutation rate (left), but body weight is not significantly associated with somatic mutation rate (right) (Image source: Reference[1])
The researchers speculate that larger animals with more cells do not have higher rates of cell mutation, suggesting that other protective factors that can help reduce cancer risk can be sought from these large animals. For example, within the elephant genome, there are 20 copies of the powerful anti-cancer gene TP53 (at least some of which are partially functional).
Another lead author, Dr. Adrian Baez-Ortega, said: "Although it seems that regulating somatic mutation rates between different species can achieve cancer incidence control, evolution does not seem to do so." It's quite possible that every time a species — such as giraffes, elephants, and whales — evolves larger than their ancestors, evolution has a different solution. We need to study these species in more detail to find out. ”
Resources:
[3] Mutations across animal kingdom shed new light on ageing Retrieved Apr. 15, 2022 from https://www.eurekalert.org/news-releases/949380
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