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Scientists Discover an On/Off Switch for Aging Cells

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Aging Cells

A human body is composed of various types of cells. These cells constantly divide so that dying cells can be replenished.  Everyday millions of red blood cells in our body die and in order to maintain a healthy circulatory system, our body needs to produce the same amount of them. The reason we age is that some cells can no longer divide. This happens because of the shortening of the cell's DNA.


The cell division is a complex process. Each time a cell divides, a small part of the cell's DNA is lost from the end of the DNA strand. In order that no genetic information is lost, there is non-coding DNA at the end of the strand which is known as telomeres. The cells stop dividing when the telomeres reach a certain length. Certain cells can divide indefinitely because of the presence of an enzyme known as telomerase. This enzymes synthesizes to produces more telomeres that attaches itself at the tail of the DNA. This makes it possible for the cell to continue dividing.


Researchers at the Salk Institute have made a break through discovery that could hold the key to healthy aging. They have found an on/off switch in the cells that could encourage healthy cells to keep dividing and multiplying to replenish dying cells. That means, even in old age lung, liver or other vital organ tissue could regenerate keeping them healthy.


The new study that has been published on September 19th in the journal Genes and Development, says that telomerase even when present can actually be turned off.


Vicki Lundblad, Senior Author, Professor and holder of Salk’s Ralph S. and Becky O’Connor Chair said that in previous studies, it was suggested that once assembled the telomerase is available only when needed. However, the present study lead to the discovery that telomerase actually has an off switch which makes the disassembly possible. This knowledge of an ˜off' switch can be crucial in developing treatments for diseases of aging. If we can understand how this off switch can be manipulated, we can slow down the telomere shortening process. It can also help us in innovating ways to regenerate vital organs later in life.


Lundblad together with first author and graduate student Timothy Tucey carried out their studies in the yeast Saccharomyces cerevisiae, the yeast that goes into making wine and bread. In previous researches, Lundblad’s group had used this simple single-celled organism to reveal various insights about telomerase and prepare the groundwork for guiding similar findings in human cells.


Tucey adds, “We wanted to be able to study each component of the telomerase complex but that turned out to not be a simple task,” That is why Tucey framed a strategy that let him to observe and study each component during cell growth and division at very high resolution. This study led to several discoveries about telomere, and how it works.


When a cell divides, its entire genome has to be duplicated. While this duplication happens, Tucey observed that telomerase sits poised as a “preassembly” complex, missing a critical molecular subunit. But as soon as the genome has been fully duplicated, the missing subunit unites with its companions to form a complete and active telomerase complex. This is the state when telomerase can replenish the ends of shortening chromosomes and ensure healthy cell division.


Interestingly, Tucey and Lundblad also discovered that immediately after the full telomerase complex has been assembled, it rapidly disassembles to form an inactive “disassembly” complex. The inactive state is achieved by flipping the so called switch into the “off” position.


The duo speculate that this disassembly pathway maybe a means to keep telomerase at exceptionally low levels inside the cell. That is because cancer cells rely on increased telomerase levels to ensure uncontrolled cell growth. The “off” switch found by Tucey and Lundblad may be the means to keep the activity below this threshold.


The development of practical applications with these discoveries is at an early stage. However, if successfully implemented, it could prove useful in providing effective treatments to age related diseases It could also be an alternative approach to using stem cells.