Telomeres are ribonucleoprotein complexes at the ends of chromosomes that are essential for chromosome protection and genomic stability. Telomeres consist of tandem TTAGGG repeats bound to a 6-protein complex known as shelterin. More recently, telomeres have been also shown to contain long non-coding telomeric RNAs (TelRNAs or TERRAs), which are associated to the telomeric chromatin and have been proposed to be potential regulators of telomerase activity and telomere length. In addition, telomeric chromatin is enriched in epigenetic marks characteristic of constitutive heterochromatin, such as histone trimethylation (H3K9 and H4K20 tri-methylation) and DNA hypermethylation, which act as negative regulators of telomere length. Telomere length defects are associated to both cancer and aging processes, and have been recently shown to have a profound effect on stem cell behaviour. Here, we propose to determine the role of both genetic and epigenetic telomere regulators in cancer and aging by generating new mouse models. Finally, we will study the role of these factors in stem cell biology.