▎ Wuxi apptec content team editor

Animal species in nature are rich and diverse, with their own characteristics. Some animals are known for their long life span. Naked mole, for example. The body size is similar to that of our common mice, but the life span of naked mole mice is more than ten times that of mice. There is such a “rule” in the animal kingdom: the larger the species, the longer the life span. But an alien like the naked mole breaks this rule. The adult of naked mole is only one 23000 times that of giraffe, but they can live for more than 20 years!

Why do some animals live longer than others? In the latest issue of nature, scientists provide clues to this enduring problem by measuring somatic mutations in animals.

Gene mutations occur continuously in cells in the body. It is estimated that human cells obtain an average of 15 ~ 40 mutations every year. Although most of them are harmless, there are always some mutations that may lead cells to cancer. With age, the accumulation of somatic mutations may drive the development of cancer, which is also considered to be an important cause of aging and other diseases.

From the perspective of somatic mutation, the longer the life span and the larger the body (the more cells), it means that more cancer risks may be accumulated. But in a recent study published in the journal Nature, scientists examined nearly 200 species of mammals with different lifespans and sizes, specifically compared their cancer death risk, and proved that those species with longer life expectancy and larger size were not more likely to die of cancer.

In other words, large and long-lived mammalian species are likely to have acquired some more effective cancer defense mechanisms in the process of evolution. This hypothesis is very exciting because it means that we may find some natural anti-cancer secrets from other animals and develop anti-cancer therapies.

▲ longevity star naked mole (picture source: 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 from Wellcome Sanger Institute in the UK made a comparative analysis of more than a dozen mammals with different lifespan and body size from the perspective of the accumulation of somatic mutations with age.

The animals analyzed this time include people, mice, dogs, giraffes, horses, tigers, dolphins, ring tailed lemurs, etc. of course, they also include the “longevity star” naked mole, a total of 16 species. The researchers collected samples from 48 individuals and uniformly obtained epithelial cells from colonic recess tissue for single-cell sequencing analysis. The whole genome data of these cells can be well used to estimate the number of mutations in a single cell every year, that is, the mutation rate of the species.

The results of genome sequencing analysis show that the rate of gene mutation in different animal somatic cells is different, and the most relevant factor is animal life span. Animals with longer lifespan get few mutations every year, and the mutation rate of cells is much slower. On the contrary, short-lived animals produce a lot of mutations every year. For example, mice produce about 17 times more somatic mutations than humans.

Interestingly, when animals of different species reach the limit of life, the total number of mutations per cell is roughly similar. “We were surprised to find that very different animals like mice and tigers have similar patterns of genetic changes,” said Dr. Alex Cagan, the first author of the study

The researchers analyzed that long-lived animals produce mutations at a relatively slow rate, which may explain why the cancer risk of long-lived animals does not increase with life.

In addition to life span, the authors also examined the factors of animal body shape, but found that there was no significant correlation between body shape and somatic mutation rate. Still looking at giraffes and naked moles, the somatic mutation rates are similar for those with similar lifespan and different body sizes. Compared with mice of similar size, the somatic mutation rate of naked mole mice was abnormally low.

The researchers speculate that large animals with more cells do not have a higher mutation rate, suggesting that other protective factors that can help reduce the risk of cancer can be found in these large animals. For example, in the elephant genome, the powerful anti-cancer gene TP53 has 20 copies (at least some of which have partial functions).

Dr. Adrian Baez Ortega, another lead author, believes that: “Although it seems that the regulation of somatic mutation rates among different species can achieve control of cancer incidence rate, it seems that evolution has not done so. It is very likely that every time a species, such as giraffe, elephant and whale, evolved a larger body than their ancestors, there was a different solution to the evolution. We need to study these species in more detail to find the answer.”

reference material:

[1] Alex Cagan et al。， （2022） Somatic mutation rates scale with lifespan across mammals。 Nature。 Doi： https：//doi. org/10.1038/s41586-022-04618-z

[2] Mutational clocks tick differently across species。 Nature。 doi： https：//doi. org/10.1038/d41586-022-00976-w

[3] Mutations across animal kingdom shed new light on ageing Retrieved Apr。 15， 20

▎ Wuxi apptec content team editor

Animal species in nature are rich and diverse, with their own characteristics. Some animals are known for their long life span. Naked mole, for example. The body size is similar to that of our common mice, but the life span of naked mole mice is more than ten times that of mice. There is such a “rule” in the animal kingdom: the larger the species, the longer the life span. But an alien like the naked mole breaks this rule. The adult of naked mole is only one 23000 times that of giraffe, but they can live for more than 20 years!

Why do some animals live longer than others? In the latest issue of nature, scientists provide clues to this enduring problem by measuring somatic mutations in animals.

Gene mutations occur continuously in cells in the body. It is estimated that human cells obtain an average of 15 ~ 40 mutations every year. Although most of them are harmless, there are always some mutations that may lead cells to cancer. With age, the accumulation of somatic mutations may drive the development of cancer, which is also considered to be an important cause of aging and other diseases.

From the perspective of somatic mutation, the longer the life span and the larger the body (the more cells), it means that more cancer risks may be accumulated. But in a recent study published in the journal Nature, scientists examined nearly 200 species of mammals with different lifespans and sizes, specifically compared their cancer death risk, and proved that those species with longer life expectancy and larger size were not more likely to die of cancer.

In other words, large and long-lived mammalian species are likely to have acquired some more effective cancer defense mechanisms in the process of evolution. This hypothesis is very exciting because it means that we may find some natural anti-cancer secrets from other animals and develop anti-cancer therapies.

▲ longevity star naked mole (picture source: 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 from Wellcome Sanger Institute in the UK made a comparative analysis of more than a dozen mammals with different lifespan and body size from the perspective of the accumulation of somatic mutations with age.

The animals analyzed this time include people, mice, dogs, giraffes, horses, tigers, dolphins, ring tailed lemurs, etc. of course, they also include the “longevity star” naked mole, a total of 16 species. The researchers collected samples from 48 individuals and uniformly obtained epithelial cells from colonic recess tissue for single-cell sequencing analysis. The whole genome data of these cells can be well used to estimate the number of mutations in a single cell every year, that is, the mutation rate of the species.

The results of genome sequencing analysis show that the rate of gene mutation in different animal somatic cells is different, and the most relevant factor is animal life span. Animals with longer lifespan get few mutations every year, and the mutation rate of cells is much slower. On the contrary, short-lived animals produce a lot of mutations every year. For example, mice produce about 17 times more somatic mutations than humans.

Interestingly, when animals of different species reach the limit of life, the total number of mutations per cell is roughly similar. “We were surprised to find that very different animals like mice and tigers have similar patterns of genetic changes,” said Dr. Alex Cagan, the first author of the study

The researchers analyzed that long-lived animals produce mutations at a relatively slow rate, which may explain why the cancer risk of long-lived animals does not increase with life.

In addition to life span, the authors also examined the factors of animal body shape, but found that there was no significant correlation between body shape and somatic mutation rate. Still looking at giraffes and naked moles, the somatic mutation rates are similar for those with similar lifespan and different body sizes. Compared with mice of similar size, the somatic mutation rate of naked mole mice was abnormally low.

The researchers speculate that large animals with more cells do not have a higher mutation rate, suggesting that other protective factors that can help reduce the risk of cancer can be found in these large animals. For example, in the elephant genome, the powerful anti-cancer gene TP53 has 20 copies (at least some of which have partial functions).

Dr. Adrian Baez Ortega, another lead author, believes that: “Although it seems that the regulation of somatic mutation rates among different species can achieve control of cancer incidence rate, it seems that evolution has not done so. It is very likely that every time a species, such as giraffe, elephant and whale, evolved a larger body than their ancestors, there was a different solution to the evolution. We need to study these species in more detail to find the answer.”

reference material:

[1] Alex Cagan et al。， （2022） Somatic mutation rates scale with lifespan across mammals。 Nature。 Doi： https：//doi. org/10.1038/s41586-022-04618-z

[2] Mutational clocks tick differently across species。 Nature。 doi： https：//doi. org/10.1038/d41586-022-00976-w

[3] Mutations across animal kingdom shed new light on ageing Retrieved Apr。 15， 20