of a degenerative phenotype. In another study, introducing the TERT gene into healthy one-year-old mice using an engineered adeno-associated virus led to a 24% increase in lifespan, without any increase in cancer. Relation to epigenetic clock Paradoxically, genetic variants in the TERT locus, which are associated with longer leukocyte telomere length, are associated with faster epigenetic aging rates in blood according to a molecular biomarker of aging known as epigenetic clock. Similarly, human TERT expression did not arrest epigenetic aging in human fibroblasts. Gene therapy The hTERT gene has become a main focus for gene therapy involving cancer due to its expression in tumor cells but not somatic adult cells. One method is to prevent the translation of hTERT mRNA through the introduction of siRNA, which are complementary sequences that bind to the mRNA preventing processing of the gene post transcription. This method does not eliminate telomerase activity, but it does lower telomerase activity and levels of hTERT mRNA seen in the cytoplasm. Higher success rates were seen in vitro when combining the use of antisense hTERT sequences with the introduction of a tumor-suppressing plasmid by adenovirus infection such as PTEN. Another method that has been studied is manipulating the hTERT promoter to induce apoptosis in tumor cells. Plasmid DNA sequences can be manufactured using the hTERT promoter followed by genes encoding for specific proteins. The protein can be a toxin, an apoptotic factor, or a viral protein. Toxins such as diphtheria toxin interfere with cellular processes and eventually induce apoptosis. Apoptotic death factors like FADD (Fas-Associated protein with Death Domain) can be used to force cells expressing hTERT to undergo apoptosis. Viral proteins like viral thymidine kinase can be used for specific targeting of a drug. By introducing a prodrug only activated by the viral enzyme, specific targeting of cells expressing hTERT can be achieved. By using the hTERT promoter, only cells expressing hTERT will be affected and this allows for specific targeting of tumor cells. Aside from cancer therapies, the hTERT gene has been used to promote the growth of hair follicles. A schematic animation for gene therapy is shown as follows. Interactions Telomerase reverse transcriptase has been shown to interact with: HSP90AA1, Ku70, Ku80, MCRS1, Nucleolin, PINX1, and YWHAQ. PAWR See also telomerase reverse transcriptase References Further reading External links GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita GeneReviews/NCBI/NIH/UW entry on Pulmonary Fibrosis, Familial Telomere-binding proteins Telomere-related proteins