Telomere extensions can potentially reverse the aging clock in artificially cultured human cells

telomeres_age-reversal

A telomere is basically a region of repetitive nucleotide sequences that are present at each end of the chromatid. It functions in protecting the end of the chromosome from deterioration or from getting fused with the chromosomes that are present in the neighborhood. To get a better view on the function of telomere, it has been compared with the plastic tips of shoelaces which protect the laces from wearing down. Telomere also in a similar way keeps the chromosome end from fraying which results in the sticking of the chromosomes with each other. This fraying would result in the destruction of the organism’s genetic information. The genetic information is so crucial that it basically has to remain throughout all the cells of the human body.

Still, each time, a cell division takes place, the telomeres keep on getting shorter. And in the end, when they get too short – the cell loses its capability to divide and becomes senescent. This process of telomere shortening has been associated with aging, cancer and higher risks of death due to lack of proper recovery. Telomeres hence are often compared to the bomb fuse that is present in every organism, but at the cellular level.

Recently researchers have developed a modified RNA that has the capability to encode a telomere extending protein that has been till now applied on cultured human cells. This protein has resulted in a dramatic increase of the proliferation capacity of the cell, and has hence yielded a large number of cells for study. This work has been supported by the National Institutes of Health, which is under Germany’s Federal Ministry of Education and Research, Stanford Bio-X and the prestigious Baxter Foundation.

According to the researchers who represent the Stanford University School of Medicine, they have observed that the culture cells that they have treated with the protein, behave as if they are much younger than the untreated cells, and have the capacity to multiply at a far higher pace than the untreated ones.

The procedure has been involving the use of a modified RNA, which is believed to improve the ability of the researchers to generate a large number of cells that are generally used in studying and drug development. They have also successfully conducted an experiment where they had treated skin cells which had lengthened telomere with the help of that procedure. It has been observed that these treated cells could divide forty times more than the normal untreated cells. On a wider scope, success in this research project could pave a new horizon in the treatment of diseases that are linked to telomere shortening.

The telomeres or the protective caps of the chromosomes measure almost 10,000 nucleotides long in healthy young humans. But this length gradually deteriorates, and after a critical length, the cells stop dividing – and as a result the cell eventually dies. However when it comes top laboratory work, this internal clock that is associated with cell aging is the phenomenon that has been a huge challenge to keep most cells growing in the laboratory.

In the words of Dr. Helen Blau, her research team has successfully been able to lengthen human telomeres by as much as 1000 nucleotides, and hence they have been successful in turning back this internal clock. This when taken to the scale of an average person – can result in many equivalent years of his life.

The modified messenger RNA used by the researchers carry instructions from genes in the DNA to the protein making site of the cells. The RNA that has been used in the experiment contains the coding sequence which is similar to TERT. TERT (or telomerase reverse transcriptase) is an active component of the naturally occurring telomerase enzyme. As an enzyme telomerase is basically exhibited in the stem cells that give rise to the sperm and egg cells, and they ensure that the chromosome remains intact for the next generation. The other types of cells however exhibit a very low amount of telomerase.

This newly developed technique has the scope of paving the path towards preventing as well as curing diseases that are related to aging. The new technique also has potential advantages when compared to other conventional matters as it has a rather temporary effect. The design of this modified RNA is such that the host cell would have lower immune response to the RNA and this would permit the sticking of the TERT encoded message a bit longer when compared to an unmodified message. But this starts to dissipate within 48 hours, and now the cells start to divide and the telomeres keep on shortening progressively.

Dr. Blau had gathered interest in telomeres after working on the muscle stem cells of boys with Duchene Muscular Dystrophy. She observed that the telomeres of the patient cells were much shorter when compared with the cells of normal boys. This finding has a serious implication on the function of telomeres on how these cells have a limited ability to grow in the absence of long telomeres. Research is still being conducted on other types of cells.

This study has gained accolades from all around the world and scientists are hopeful of this study to be a first step towards the development of telomere extensions to improve cell therapy and treat disorders, especially the ones that are related to accelerated aging.

Source/ Image Credit: Stanford University School of Medicine

This is a guest post written by Aritra Bandyopadhyay. He has a Masters degree in Bio-chemistry, and has worked as a marketing executive at Ranbaxy. Currently, he is pursuing his PGDBA in Marketing and HR from SCDL.

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