DNA analysis of 115 year old woman reveals human life limits

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Many genetic mutation studies are done to determine their links to chronic diseases, but not much is known about the mutations that take place in healthy individuals.

Researchers from New York studied the healthy blood cells of a woman aged 115, finding that there were 400 mutations present, but her body was able to tolerate them. This means that it did not cause disease and this finding may provide clues about longevity for humans.

Blood in the human body is constantly replenished by hematopoietic stem cells which are located in bone marrow. The cells split to build different blood cell types, including the white blood cells. However, cell division comes with problems and the cells that split the most, including the blood, often develops genetic mutations.

Patients with cancer of the blood often indicate hundreds of mutations, but it is not clear if healthy white blood cells have the same mutations.

Researchers at the Cold Spring Harbor Laboratory used whole genome sequencing of the 115-year-old’s white blood cells to find out if after such a long lifetime, mutations had accumulated in healthy white blood cells.

They discovered in excess of 400 mutations in her white blood cells which were not present in her brain. The brain is the one part of the body that very rarely experiences cell division after birth.

The mutations are known as somatic mutations because they are not transmitted to offspring. They appear to be well tolerated by the body and do not cause disease. The mutations were found to be in the regions of the genome which was not previously linked to disease.

By doing an examination of the white cells which contained the mutations, a major discovery was made which may hint at human longevity limits.

The lead author of this study, Dr Henne Holsetege, said that at the time of the old woman’s death, the peripheral blood was obtained from only two of the active hematopoietic stem cells, in sharp contrast to an estimated 1,300 stem cells that were simultaneously active, which were linked to each other.

The researchers examined the sequences at the ends of the chromosomes that protect the cells. The sequences shorten each time the cells divide, after birth. The indication was that the white blood cell sequences were much shorter than those in the brain.

Dr Holsetege stated that the short sequences of the blood cells prompted speculation that most of the haematopoietic stem cells possibly died due to ‘stem cell exhaustion’.

Future studies will target the determination of whether stem cell exhaustion is possibly the cause of death at extremely advanced ages.

The white blood cells used during this study was a donation by a super-centenarian female, Hendrikje van Andel-Schipper. At the time of her death during 2005, she was classified as the oldest person in the world and most likely the oldest person ever to have donated her body to scientific research.

Image Credit: Tareq Salahuddin

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