Telomerase Biology Associations offer Keys to Cancer and Aging Therapeutics.

Although telomerase has potential for intervention in age-related diseases, the increased telomerase in about 90% of cancers, cautions against development of anti-aging therapeutics. The review here summarizes the multiple TERT (telomerase reverse transcriptase) telomerase subunit's unique associations that regulate cell functions that impact aging, cancer, and therapeutics. The TERT associations include proper folding, intracellular TERT transport, metabolism, mitochondrial ROS function, inflammation, cell division, cell death, and gene expression, in addition to the well-known telomere maintenance. While increase of cell cycle inhibitors promote aging, in cancer, the cell cycle check-point regulators are ambushed in favor of cell proliferation, while cytoplasmic TERT protects a cell cycle inhibitor in oxidative stress. The oncogene cMyc regulates gene expression for increased expression of TERT, and reduction of cell cycle inhibitors-the perfect storm for cancer promotion. TERT binds with the oncogene RMRP RNA, and TERT-RMRP function can regulate levels of that oncogene RNA. The discovery that GV1001, a 16 amino acid peptide of TERT, used to develop the vaccine against cancer, unexpectedly, bypasses the cell membrane, and with HSPs, and can transport intra-cellular cargo drugs that intervene in cancer, viral infection, and antiaging diseases, i.e. the "birth" of a miracle form of telomerase. The evolution of "smart drugs" offers the unprecedent ability to target of chemotherapy to only cancer cells. The review overall, argues for appropriate development of therapeutic intervention of telomerase in age related diseases especially in neurology and cardiology.