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Stem cell 'exhaustion' may play role in human lifespan

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Stem cell “exhaustion” may play a role in defining the limit of human lifespan, a study of blood from a dead Dutch super-centenarian suggests.

Analysis of white blood cells from 115-year-old Hendrikje van Andel-Schipper showed they were derived from just two related stem cell clones.

In a younger adult an estimated population of 10,000-20,000 “haematopoietic” stem cells produce “offspring” that replenish all the different kinds of blood cell.

Mrs van Andel-Schipper’s white blood cells also had much shorter “telomeres” − protective caps on the ends of chromosomes that shorten with age − than her brain cells.

“Most haematopoietic stem cells may have died from ‘stem cell exhaustion’”

Henne Hostege

When telomeres get sufficiently short, cells stop renewing themselves and may die.

“Because these blood cells had extremely short telomeres, we speculate that most haematopoietic stem cells may have died from ‘stem cell exhaustion’, reaching the upper limit of stem cell divisions,” said lead scientist Dr Henne Hostege, from Cold Spring Harbor Laboratory in the US.

Future studies were needed to see whether stem cell exhaustion might be a cause of death at extreme ages, said the scientists, whose findings are published in the journal Genome Research.

The researchers also identified more than 400 genetic mutations in the white blood cells which appeared to be harmless, unlike those found in patients with blood cancers such as leukaemia.

Hendrikje van Andel-Schipper

Hendrikje van Andel-Schipper

At the same time, they were not thought to confer any advantage that might have helped Mrs van Andel-Schipper to live such a long life.

The “somatic” mutations which are not passed on to offspring were mainly in non-coding regions of DNA not associated with disease.

At the time of her death in 2005, Mrs van Andel-Schipper, known as “Henny”, was officially the oldest person in the world. At the age of 82, she gave written consent for her body to be donated to science after her death.

A study of her brain found little sign of the changes normally associated with great age and no trace of Alzheimer’s disease. Scientists have also sequenced the whole of her genetic code.

Mrs van Andel-Schipper had surgery for breast cancer at the age of 100, and died 15 years later as a result of a gastric tumour that spread to her abdomen.

Since she never received mutation-inducing chemotherapy, the mutations seen in her DNA were purely due to normal ageing, said the scientists.

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