Ageing breakthrough: Scientists create “hyper-long” telomeres without gene editing

Scientists have successfully created mice with significantly longer telomeres than normal, resulting in a drop in molecular ageing, without using genetic manipulation.

Telomeres, which are found at the end of all animals’ chromosomes, are thought to be vital to ending ageing, as their shortening as we age is a key factor in cellular ageing and the onset of age-related disease. However, when they are lengthened beyond normal levels in mice, they have the precise opposite effect, protecting against ageing and related diseases, and increasing lifespan.

The mice, which are chimeras carrying both regular and “hyper-long” telomeres, were created using a technique based on epigenic changes, where embryonic stem cells are expanded in vitro, prompting changes to telomeres.

“The in vitro expansion of the embryonic stem cells results in the elongation of the telomeres up to twice their normal length,” explained the authors of the study, which is published today in the journal Nature Communications.

First demonstrated in cells alone in 2009, and in embryonic stem cells in 2011, this current research by scientists at the Spanish National Cancer Research Centre (CNIO) is the first to produce hyper-long telomeres in living mice. As a result, the study authors said that this “proof of concept means that it is possible to generate adult tissue with longer telomeres in the absence of genetic modifications”.

The eye of one of the chimera mice, with hyper-long telomere-containing cells marked in green.

Cells from the eye of one of the chimera mice, with hyper-long telomere-containing cells marked in green.

The cells with lengthened telomeres have been declared by the researchers to be “perfectly functional”, having been analysed at 0, 1, 6 and 12 months.

The cells were found to have maintained their length, demonstrating normal shortening over time, while acquiring less DNA damage and better repairing abilities. The mice also had fewer tumours than their normal counterparts.

“Our work also demonstrates that it is possible to generate iPS cells with longer telomeres that would turn into differentiated cells also with longer telomeres and that would, therefore, be better protected against damage,” added study lead author Maria A Blasco.

Intestinal cells from a chimera mouse, with cells containing hyper-long telomeres marked in green. Image courtesy of Spanish National Cancer Research Centre (CNIO)

Intestinal cells from a chimera mouse, with cells containing hyper-long telomeres marked in green. Image courtesy of Spanish National Cancer Research Centre (CNIO)

In time the research could lead to treatments for ageing and age-related diseases in humans, however this is a considerable way away.

While the research is significant, there is inevitably more work to be done. The next step, according to Blasco and colleague Elisa Varela, is to “generate a new species of mice in which the telomeres of all the cells are twice as long as those in normal mice”.

“Then, we will be able to address some of the important questions that remain unanswered: would a mouse species with telomeres that are double in length live longer?” they asked.

“Is this the mechanism that is used by nature to determine different longevities in genetically similar species? Would this new species present a higher or lower incidence of cancer?”

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