Mutations in the animal kingdom shed new light on aging

Somatic cell gene mutations

Somatic cells in an organism are all body cells except germ cells. All body cells of an individual have the same genotype and the same number of chromosomes. For human body cells, this chromosome number is 46, which in reality corresponds to 22 pairs of homologous chromosomes and 1 pair of sex chromosomes.

During embryonic development and then during growth, cells multiply by cell division. This step, which allows the formation of two daughter cells from a single cell, is preceded by the process of DNA replication.

During this process, DNA is replicated into two DNA molecules that are identical to the original molecule. These molecules are distributed to each new daughter cell during mitosis.

DNA replication can cause mutations in the sequences of certain genes. One could compare this to errors that occur when copying DNA. Fortunately, many of these mutations can be repaired by cellular engineering that has the necessary tools. In many cases, even if they are not repaired, these genetic mutations within body cells have no effect and go completely unnoticed.

Somatic mutations occur in all cells of the organism throughout life. This is largely a natural process, although exposure to certain substances called mutagens, such as UV rays, radiation, or certain chemicals, can inadvertently cause mutations.

In some cases, these genetic mutations can change the function of a gene and lead to cellular dysfunction. Very often the cell dies, but these genetic disorders can also cause the uncontrollable cell to multiply, which then becomes cancerous.

>> Also read: Discoveries about the genetic mutation that made our brains grow

An analysis of the genomes of 16 animal species

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Scientists at the Wellcome Trust Sanger Institute have analyzed the genomes of 16 animal species to determine rates of somatic mutations

Source: angellodeco/Shutterstock

Caption: Scientists at the Wellcome Trust Sanger Institute analyzed the genomes of 16 species of animals to determine rates of somatic mutations. Source: angellodeco/Shutterstock

Since the 1950s, a number of geneticists have hypothesized that somatic mutations play a role in the aging of individuals. This hypothesis remained unverifiable for a long time due to the lack of opportunities to observe genetic mutations. Technological advances in the field of genetics and genome analysis have made it possible to observe these mutations in recent years.

In their work, geneticists at the Wellcome Trust Sanger Institute set out to identify and measure somatic mutations for 16 species of mammals to obtain a wide range of size and weight. Humans, mice, lions, tigers, giraffes and mole rats are among those affected. The latter was chosen because it is an animal known to be resistant to cancer and has a long lifespan.

To obtain the entire genome of the people tested, the researchers used cells from samples of a small amount of intestinal tissue. With these samples, they were able to measure the mutation rates in the stem cells of the intestine. These cells are located at the base of the crypt, which is the deepest point of an intestinal villus. They are constantly dividing to renew the intestinal epithelium.

By analyzing the genome of somatic cells from these gut samples, the scientists found that mutations accumulate linearly over time and are caused by the same mechanisms, regardless of species.

Finally, the role of these mutations in aging was demonstrated by noting that the mutation rate decreases with increasing lifespan.

>> Also read: How does DNA analysis work?

Lifespan is inversely proportional to somatic mutation rate

Since the 1950s, a number of geneticists have hypothesized that somatic mutations play a role in the aging of individuals. This hypothesis remained unverifiable for a long time due to the lack of opportunities to observe genetic mutations. Technological advances in the field of genetics and genome analysis have made it possible to observe these mutations in recent years.

In their work, geneticists at the Wellcome Trust Sanger Institute set out to identify and measure somatic mutations for 16 species of mammals to obtain a wide range of size and weight. Humans, mice, lions, tigers, giraffes and mole rats are among those affected. The latter was chosen because it is an animal known to be resistant to cancer and has a long lifespan.

To obtain the entire genome of the people tested, the researchers used cells from samples of a small amount of intestinal tissue. With these samples, they were able to measure the mutation rates in the stem cells of the intestine. These cells are located at the base of the crypt, which is the deepest point of an intestinal villus. They are constantly dividing to renew the intestinal epithelium.

By analyzing the genome of somatic cells from these gut samples, the scientists found that mutations accumulate linearly over time and are caused by the same mechanisms, regardless of species.

Finally, the role of these mutations in aging was demonstrated by noting that the mutation rate decreases with increasing lifespan.

>> Also read: How does DNA analysis work?

What was most amazing for the researchers was finding a similar mechanism of genetic mutation in animals as different as lions and mice, but also realizing that lifespan is inversely proportional to the number of mutations. This undoubtedly means that somatic cell mutations play a role in the aging process.

Geneticists have also found that despite large differences in lifespan and body mass between species, the number of somatic mutations acquired over a lifetime is relatively similar, regardless of species. For example, a giraffe is 40,000 times larger than a mouse, but the difference in the number of mutations over the lifespan of these two animals varies very little.

The researchers will continue their work, particularly to find an answer to Peto’s paradox, which states that since cancer develops from a single cell, species with a larger body and therefore more cells should pose a much higher risk of cancer. However, this is not the case, and scientists believe that large animals have evolved other mechanisms to prevent cancer.

Aging remains a complex process that is likely the result of various types of damage to the molecules of our cells and tissues. Understanding its exact causes remains an active research topic.

>> Also read: Eczema: Two genetic mutations favor its occurrence

Source: Cagan, A., Baez-Ortega, A., Brzozowska, N. et al.“Somatic mutation rates scale with lifespan in mammals”, Nature (2022), https://doi.org/10.1038/s41586-022-04618-z

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