The Telomeres and Telomerase Group at the Spanish National Cancer Research Centre (CNIO), in collaboration with the Centre’s Transgenic Mice Core Unit, has succeeded in creating mice in the laboratory 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 today in the pages of 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.
Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with ‘hyper-long’ telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression.