Hundreds of genetic mutations found in healthy blood of a supercentenarian

Early hematopoietic stem cells (blue) in a blood vessel of a mouse embryo. Credit: Nancy Speck, University of Pennsylvania School of Medicine

Genetic mutations are commonly studied because of links to diseases such as cancer; however, little is known about mutations occurring in healthy individuals. In a study published online in Genome Research, researchers detected over 400 mutations in healthy blood cells of a 115-year-old woman, suggesting that lesions at these sites are largely harmless over the course of a lifetime.

Our blood is continually replenished by that reside in the bone marrow and divide to generate different types of blood cells, including . Cell division, however, is error-prone, and more frequently dividing cells, including the blood, are more likely to accumulate . Hundreds of mutations have been found in patients with blood cancers such as acute myeloid leukemia (AML), but it is unclear whether healthy white blood cells also harbor mutations.

In this new study, the authors used whole genome sequencing of white blood cells from a supercentenarian woman to determine if, over a long lifetime, mutations accumulate in healthy white blood cells. The scientists identified over 400 mutations in the white blood cells that were not found in her brain, which rarely undergoes cell division after birth. These mutations, known as because they are not passed on to offspring, appear to be tolerated by the body and do not lead to disease. The mutations reside primarily in non-coding regions of the genome not previously associated with disease, and include sites that are especially mutation-prone such as methylated cytosine DNA bases and solvent-accessible stretches of DNA.

By examining the fraction of the white blood cells containing the , the authors made a major discovery that may hint at the limits of human longevity. "To our great surprise we found that, at the time of her death, the peripheral blood was derived from only two active hematopoietic stem cells (in contrast to an estimated 1,300 simultaneously active stem cells), which were related to each other," said lead author of the study, Dr. Henne Holstege.

The authors also examined the length of the telomeres, or repetitive sequences at the ends of chromosomes that protects them from degradation. After birth, telomeres progressively shorten with each . The white blood cell telomeres were extremely short

More information: Holstege H, Pfeiffer W, Sie D, Hulsman M, Nicholas TJ, Lee CC, Ross T, Lin J, Miller MA, Ylstra B, Meijers-Heijboer H, Brugman MH, Staal FJT, Holstege G, Reinders MJT, Harkins TT, Levy S, Sistermans EA. 2014. Somatic mutations found in the healthy blood compartment of a 115-year-old woman demonstrate oligoclonal hematopoiesis. Genome Res doi: 10.1101/gr.162131.113

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Returners
1 / 5 (1) Apr 23, 2014
The authors also examined the length of the telomeres, or repetitive sequences at the ends of chromosomes that protects them from degradation. After birth, telomeres progressively shorten with each cell division. The white blood cell telomeres were extremely short


This bothers me, because in another article a few weeks ago about GM yeast, the scientists were described as removing "junk DNA", including some redundant genes. I think that was a bad idea, as having redundant genes protects against catastrophic mutations, and having some "padding" between genes (which they call "junk") would also help protect against catastrophic negative mutations.

It would seem to me that if people wanted to genetically engineer life forms to live longer, then artificially adding to the telomeres might be a good way to go.

I guess it could also offer a path for future nanotech (very far I think) in that we could design machine-like proteins and enzymes to physically repair the telomeres...
qquax
5 / 5 (1) Apr 24, 2014
Returners, nature already has an enzyme to repair telomeres aptly called telomerase. There also exists an entire cottage industry based on food supplements (prime amongst them Resveratrol), that aims at increasing the telomerase activity within the human cells.

Osiris1
not rated yet Apr 24, 2014
We should look for a code among the 'junk DNA' that has a message for us when we get advanced enough in computer science to find it.
tadchem
not rated yet Apr 24, 2014
I recently did a 'back-of-the-envelope' calculation that estimated that naturally occurring radioactive carbon-14, incorporated in the DNA of living cells, decays at a rate that would cause roughly 10 *certain* DNA changes every 3 seconds in an adult human.
Over a 115 year lifetime that would total about 1.2 billion changes in the DNA, solely from the unavoidable radioactivity of carbon-14 in food.
Returners
1 / 5 (1) Apr 24, 2014
We should look for a code among the 'junk DNA' that has a message for us when we get advanced enough in computer science to find it.


Yeah, Orphan Black bar code.

I think our Creator would want the code to be obvious, so it will probably involve a short sequence of counting numbers or primes, followed by the symbolic definition of true and false, plus a short message. I suspect 3 bases, a codon corresponding to 64 possibilities, would be enough for an intelligent creator to form a robust counting system, alphabet, and several additional symbols for punctuation and other forms of information (logic).

How many counting numbers followed by how many primes would be sufficient to convince you it was from a creator? 1-10 and first 10 primes? Or 0-63 followed by all primes within the first 63 counting numbers?

0, 1, 2, 3, 4...63
1, 2, 3, 5, 7, 11, 13...61

Of course, that's a very large piece of DNA already, so the message would be pretty short the more "confirmation" you have.
Huns
5 / 5 (1) Apr 25, 2014
I think our Creator would want the code to be obvious,
Why would a hypothetical Creator hide a message in DNA when it could instead make its presence known in an obvious, unambiguous way? What would be the point of making the evidence impossible to get to until a great deal of technology had been developed? Was everyone since the beginning of time unworthy to receive this evidence? If so, why?