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Telomere extension turns back aging clock in cultured human cells.

STANFORD, Calif., January 23, 2015--A new procedure can quickly and efficiently increase the length of human telomeres, the protective caps on the ends of chromosomes that are linked to aging and disease, according to scientists at the Stanford University School of Medicine.

Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying.

The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development, the scientists say. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases caused by shortened telomeres.

Telomeres are the protective caps on the ends of the strands of DNA called chromosomes, which house our genomes. In young humans, telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division, however, and when they reach a critical length the cell stops dividing or dies. This internal "clock" makes it difficult to keep most cells growing in a laboratory for more than a few cell doublings.

"Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life," said Helen Blau, professor of microbiology and immunology at Stanford.

"This greatly increases the number of cells available for studies such as drug testing or disease modeling." The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell's protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase. Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.

The newly developed technique has an important advantage over other potential methods: It's temporary. The modified RNA is designed to reduce the cell's immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would. But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division.

"This new approach paves the way toward preventing or treating diseases of aging," said Blau.

"There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment."

The researchers are now testing their new technique in other types of cells.

Citation: J. Ramunas et al.; "Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells"; The FASEB Journal, 2015; DOI: 10.1096/fj. 14-259531

Abstract:

http://dx.doi.org/10.1096/fj.14-259531

Contact: Helen M. Blau, hblau@stanford.edu

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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Business News
Date:Feb 9, 2015
Words:513
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