Tag Archives: telomere

BigBang

Good Mutations and Breathing

Van_andel_113

Stem cells — the factories that manufacture all our component body parts — may hold a key to divining why our bodies gradually break down as we age. A new body of research shows how the body’s population of blood stem cells mutates, and gradually dies, over a typical lifespan. Sometimes these mutations turn cancerous, sometimes not. Luckily for us, the research is centered on the blood samples of Hendrikje van Andel-Schipper — she died in 2005 at the age of 115, and donated her body to science. Her body showed a remarkable resilience — no hardening of the arteries and no deterioration of her brain tissue.  When quizzed about the secret of her longevity, she once retorted, “breathing”.

From the New Scientist:

Death is the one certainty in life – a pioneering analysis of blood from one of the world’s oldest and healthiest women has given clues to why it happens.

Born in 1890, Hendrikje van Andel-Schipper was at one point the oldest woman in the world. She was also remarkable for her health, with crystal-clear cognition until she was close to death, and a blood circulatory system free of disease. When she died in 2005, she bequeathed her body to science, with the full support of her living relatives that any outcomes of scientific analysis – as well as her name – be made public.

Researchers have now examined her blood and other tissues to see how they were affected by age.

What they found suggests, as we could perhaps expect, that our lifespan might ultimately be limited by the capacity for stem cells to keep replenishing tissues day in day out. Once the stem cells reach a state of exhaustion that imposes a limit on their own lifespan, they themselves gradually die out and steadily diminish the body’s capacity to keep regenerating vital tissues and cells, such as blood.

Two little cells

In van Andel-Schipper’s case, it seemed that in the twilight of her life, about two-thirds of the white blood cells remaining in her body at death originated from just two stem cells, implying that most or all of the blood stem cells she started life with had already burned out and died.

“Is there a limit to the number of stem cell divisions, and does that imply that there’s a limit to human life?” asks Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, who headed the research team. “Or can you get round that by replenishment with cells saved from earlier in your life?” she says.

The other evidence for the stem cell fatigue came from observations that van Andel-Schipper’s white blood cells had drastically worn-down telomeres – the protective tips on chromosomes that burn down like wicks each time a cell divides. On average, the telomeres on the white blood cells were 17 times shorter than those on brain cells, which hardly replicate at all throughout life.

The team could establish the number of white blood cell-generating stem cells by studying the pattern of mutations found within the blood cells. The pattern was so similar in all cells that the researchers could conclude that they all came from one of two closely related “mother” stem cells.

Point of exhaustion

“It’s estimated that we’re born with around 20,000 blood stem cells, and at any one time, around 1000 are simultaneously active to replenish blood,” says Holstege. During life, the number of active stem cells shrinks, she says, and their telomeres shorten to the point at which they die – a point called stem-cell exhaustion.

Holstege says the other remarkable finding was that the mutations within the blood cells were harmless – all resulted from mistaken replication of DNA during van Andel-Schipper’s life as the “mother” blood stem cells multiplied to provide clones from which blood was repeatedly replenished.

She says this is the first time patterns of lifetime “somatic” mutations have been studied in such an old and such a healthy person. The absence of mutations posing dangers of disease and cancer suggest that van Andel-Schipper had a superior system for repairing or aborting cells with dangerous mutations.

Read the entire article here.

Image: Hendrikje van Andel-Schipper, aged 113. Courtesy of Wikipedia.

BigBang

Telomere Test: A Date With Death

In 1977 Elizabeth Blackburn and Joseph Gall, molecular biologists, discovered the structure of the end caps, known as telomeres, of chromosomes. In 2009, Blackburn and colleagues Carol Greider and Jack Szostak shared the Nobel prize in Physiology or Medicine for discovering the enzyme telomerase, the enzyme responsible for replenishing telomeres.

It turns out that telomeres are rather important. Studies shows that telomeres regulate cell division, and as a consequence directly influence aging and life span. When a cell divides the length of its chromosomal telomeres shortens. Once a telomere is depleted its chromosome, and DNA, can no longer be replicated accurately, and the cell no longer divides, hastening cell death.

[div class=attrib]From the Independent:[end-div]

A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.

The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.

Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.

This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.

Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.

Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.

“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.

The researchers tested the average telomere lengths of a population of 320 Seychelles Warblers living on the remote Cousin Island, which ornithologists have studied for 20 years, documenting the life history of each bird.

“Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age,” says the study published in the journal Molecular Ecology.

Studying an island population of wild birds was important because there were no natural predators and little migration, meaning that the scientists could accurately study the link between telomere length and a bird’s natural lifespan.

“We wanted to understand what happens over an entire lifetime, so the Seychelles warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right into old age,” Dr Richardson said.

“We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year,” he said.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Infographic courtesy of Independent.[end-div]

BigBang

When Will I Die?

Would you like to know when you will die?

This is a fundamentally personal and moral question which many may prefer to keep unanswered.  That said, while scientific understanding of aging is making great strides it cannot yet provide an answer to the question. Though it may only be a matter of time.

Giles Tremlett over at the Guardian gives us a personal account of the fascinating science of telomeres, the end-caps on our chromosomes, and why they potentially hold a key to that most fateful question.

[div class=attrib]From the Guardian:[end-div]

As a taxi takes me across Madrid to the laboratories of Spain’s National Cancer Research Centre, I am fretting about the future. I am one of the first people in the world to provide a blood sample for a new test, which has been variously described as a predictor of how long I will live, a waste of time or a handy indicator of how well (or badly) my body is ageing. Today I get the results.

Some newspapers, to the dismay of the scientists involved, have gleefully announced that the test – which measures the telomeres (the protective caps on the ends of my chromosomes) – can predict when I will die. Am I about to find out that, at least statistically, my days are numbered? And, if so, might new telomere research suggesting we can turn back the hands of the body’s clock and make ourselves “biologically younger” come to my rescue?

The test is based on the idea that biological ageing grinds at your telomeres. And, although time ticks by uniformly, our bodies age at different rates. Genes, environment and our own personal habits all play a part in that process. A peek at your telomeres is an indicator of how you are doing. Essentially, they tell you whether you have become biologically younger or older than other people born at around the same time.

The key measure, explains María Blasco, a 45-year-old molecular biologist, head of Spain’s cancer research centre and one of the world’s leading telomere researchers, is the number of short telomeres. Blasco, who is also one of the co-founders of the Life Length company which is offering the tests, says that short telomeres do not just provide evidence of ageing. They also cause it. Often compared to the plastic caps on a shoelace, there is a critical level at which the fraying becomes irreversible and triggers cell death. “Short telomeres are causal of disease because when they are below a [certain] length they are damaging for the cells. The stem cells of our tissues do not regenerate and then we have ageing of the tissues,” she explains. That, in a cellular nutshell, is how ageing works. Eventually, so many of our telomeres are short that some key part of our body may stop working.

The research is still in its early days but extreme stress, for example, has been linked to telomere shortening. I think back to a recent working day that took in three countries, three news stories, two international flights, a public lecture and very little sleep. Reasonable behaviour, perhaps, for someone in their 30s – but I am closer to my 50s. Do days like that shorten my expected, or real, life-span?

[div class=attrib]Read more of this article here.[end-div]

[div class]Image: chromosomes capped by telomeres (white), courtesy of Wikipedia.[end-div]