Revitalizing cultured cells

Graphic by Kailey Trevithick

Researchers from Stanford University have developed a way to extend the life of human cells grown in culture. The technique is a quick and efficient way of increasing the number of times a cell can divide by temporarily extending the cell’s telomeres.

When a cell divides, it first has to replicate its strands of DNA. Unfortunately, the linear structure of most animal DNA results in small portions from the ends being lost with each replication. Our DNA has protective caps known as telomeres which act as a buffer for this loss.

Human telomeres are composed of thousands of short tandem repeats of the DNA sequence TTAGGG. As the telomeres shorten with each cell division, they eventually get to the point where they signal for the cell to stop dividing, known as senescence, or to die, known as apoptosis. This typically happens after 50 cell divisions.

Telomerase is an RNA-protein complex that has the ability to extend telomeres. It does this by using its RNA as a template for extension, and is extended by its protein component.

The research, published in the FASEB Journal, describes a procedure which introduces a modified molecule of messenger RNA (mRNA), which tells the cell to create telomerase reverse transcriptase (TERT), a portion of telomerase required for activity.

With three treatments spread over a couple of days, the protocol successfully increases the telomeres of skin cells, allowing the cells to divide up to 40 times more than usual.

Researchers have extended telomeres in cell culture before, but this new technique is promising because it only extends telomeres temporarily. This is important because, in addition to short telomeres, telomeres that are too long can also be harmful.

The mRNA used in the study was modified to increase its stability. It remained active for one to two days, after which, the telomeres resumed shortening. Continuous telomerase activity may lead to cell immortality, like in cancerous cells, which is caused by uncontrolled cell multiplication. These cells, however, showed normal senescence after considerable cell division.

As well as acting as a buffer area for DNA, telomeres are very strong. They protect DNA molecules from destruction and unwanted fusion events with other molecules. One way to think of telomeres is that they act like an internal countdown clock, as they play an important role in aging.

Normal DNA is composed of two strands running in opposite directions, forming a double helix. Telomeres are interesting because the terminal end is single stranded and rich in the nucleotide guanosine (G). This region contributes to the stability of telomeres, as it can arrange itself into a strong structure known as a G-quadruplex, which forms when the strand snakes around upon itself. To keep things even tighter, the ends ties themselves in protective loops.

Telomerase activity is first seen during human development, and is present in the developing cells of an embryo up until about 20 weeks. In adults, telomerase is transiently active in certain cell types, and is fully active in stem cells and germ line cells. Constitutive telomerase activity is not good. Tumour cells constitutively express telomerase and, as a result, can replicate indefinitely.

Moving forward, the team plans on using this procedure on different cell types. Hopefully this technique opens new options in the treatment of diseases related to aging and telomere dysfunction, like cancer.