Telomeres (the protective structures located at the ends of chromosomes) are essential to the stability of our genetic material and to maintain the "youthful state" of our cells and of our bodies. However, telomeres get shorter as we age. Once they reach a critical length, cells enter a state of senescence or die. This is one of the molecular causes of cellular ageing and of the emergence of ageing-related diseases.
Now researchers have succeeded in creating mice in the laboratory from stem cells with hyper-long telomeres and with reduced molecular ageing, avoiding the use of what to date has been the standard method: genetic manipulation. This new technique based on epigenetic changes that is described in the journal Nature Communications, avoids the manipulation of genes in order to delay molecular ageing. The study also underlines the importance of this new strategy in generating embryonic stem cells and iPS cells with long telomeres for use in regenerative medicine.
"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. A lengthening that occurs thanks to the active natural mechanisms without alterations in the telomerase gene.
However, would these cells be capable of developing into a mouse with telomeres that are much longer than normal and that would age more slowly? In the paper published today in Nature Communications, proves that this is the case.
The cells with hyper-long telomeres in these mice appear to be perfectly functional. When the tissues were analysed at various moments (0, 1, 6 and 12 months of life), these cells maintained the additional length scale (they shortened over time but at a normal rhythm), accumulated less DNA damage and had a greater capacity to repair any damage. In addition, the animals presented a lower tumor incidence than normal mice.
In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. Authors further show that wound-healing rates in the skin are increased.
These results show that pluripotent stem cells that carry hyper-long telomeres can give rise to organisms with telomeres that remain young at the molecular level for longer. According to the authors, this "proof of concept means that it is possible to generate adult tissue with longer telomeres in the absence of genetic modifications".
The next step for the Group is already working on will be to "generate a new species of mice in which the telomeres of all the cells are twice as long as those in normal mice", explains the author.
Mice with hyper-long telomeres created!
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