The Golden Mean

The telomeres of healthy stem cells should not be shorter or longer, but just right

Daria Zagorskaya, Vesti, based on Salk News: The Goldilocks effect in aging research

The micrograph shows the results of immunofluorescence analysis of pluripotency markers of stem cells obtained from skin fibroblasts – Nanog (red) and TRA-1-60 (green). DNA is marked in blue. Photo by Salk Institut

Since scientists discovered that aging depends on the size of the end sections of chromosomes, or telomeres, both individual cells and the body as a whole, a real race has begun in this area. One of the coveted goals was the search for factors that are involved in the regulation of telomere length.

In 1971, Soviet scientist Alexey Matveyevich Olovnikov for the first time suggested that with each new cell division, telomeric areas shrink and cells gradually age and die. Experimental confirmation of this theory was received only in 1998, for which in 2009 Elizabeth Blackburn, Carol Greider and Jack Shostak received the Nobel Prize.

But stem cells have a mechanism that protects the ends of chromosomes from constant contraction. It is based on the work of the enzyme telomerase. It is the ability to restore their telomeres that allows stem cells to retain the ability to divide indefinitely and develop into any type of body cells, be it skin, liver or heart (this "skill" is called pluripotency). Unfortunately, cancer cells also have a similar molecular tool, which makes it extremely difficult to fight them.

A team of scientists from the Salk Institute for Biological Research, led by Jan Karlseder, first experimented with reducing the length of telomeres in human embryonic stem cell cultures. Their main "limitation of telomere length in our experiments led to the loss of pluripotency by stem cells and even to their death," says the lead author of the study Teresa Rivera in a press release from the institute. – So, we decided to find out whether the ability to pluripotence will increase if we lengthen them. Surprisingly, we found that elongated telomeres become unstable and cause DNA to accumulate damage."

Continuing to understand the molecular mechanisms, the researchers found that the pruning of very long telomeres is controlled by two proteins – XRCC3 and Nbs1. Later it turned out that a decrease in their production in embryonic stem cells prevents telomere shortening. That is, for the normal functioning of the stem cell, it is necessary that the length of the end sections of the chromosomes be strictly defined, no more and no less than necessary.

At the next stage, biologists took pluripotent stem cells, which were obtained by reprogramming already differentiated (defined with functions) cells, for example, skin cells. Protein markers of telomere trimming were also found in them, which indicates the success of the reprogramming procedure itself, which is considered a huge scientific success.

It is such pluripotent stem cells that represent the main hope for regenerative medicine. This material is much more accessible to scientists, primarily from an ethical point of view, since it has nothing to do with human embryos. Secondly, the original cells can be obtained from that particular person who needs a transplant of the final stem cells, which means they will not be rejected.

"Stem cells obtained by reprogramming are a major scientific breakthrough, but methods are still being improved. Understanding exactly how telomere length is regulated is an important step towards the realization of stem cell therapy and regenerative medicine, which has long been promised to mankind," Rivera sums up his work.

You can learn more about the results of the study and the conclusions of the authors by reading the article by Rivera et al. A balance between elongation and trimming regulates telomere stability in stem cells, published in the journal Nature Structural & Molecular Biology.

Portal "Eternal youth" http://vechnayamolodost.ru  07.12.2016