Telomerase regulation and the intimate relationship with aging

Garrett Morgan1–31Department of Physiology, University of Utah School of Medicine, University of Utah, 2George E. Wahlen Department of Veterans Affairs Medical Center, 3Geriatric Research, Education and Clinical Center, VA Salt Lake City Health Care System, Salt Lake City, UT, USAAbstract: Advancing age in humans is associated with a decline in function of physiological systems, as well as the onset and progression of many chronic diseases. An ongoing focus of basic aging research is to identify biomarkers that could be used to assess the severity of age-related diseases or that could also be modulated to treat them. Telomerase is an enzyme with mechanistic links to telomere length homeostasis and cell viability. Human telomerase is a ribonucleoprotein complex that consists of its catalytic subunit (hTERT) and ribonucleic acid template (hTERC). Telomerase adds de novo TTAGGG repeats to the ends of telomeres, which may prevent telomere shortening and subsequent dysfunction in certain cell compartments. Telomerase function within the cell represents a growing area of interest among biologists who study human aging, due to its potential use as a biomarker and therapeutic target for chronic disease. Here I review the basic biology of telomerase and the consequences of telomerase overexpression and deficiency in human cells and animal models. I discuss the putative role of telomerase in telomere-length homeostasis with advancing age in humans. Finally, I describe novel nontelomeric activities of telomerase related to cell viability and mitochondrial function.Keywords: chronic disease, inflammation, oxidative stress, hTERT, hTERC, mitochondria