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ORIGINAL RESEARCH ARTICLE

Upregulation of Telomerase Function During Tissue Regeneration

Lynne W. Elmore^*,,¶, Michelle W. Norris^||, Sohini Sircar, A. Taylor Bright, Patricia A. McChesney^*,1, Richard N. Winn^|| and Shawn E. Holt^*,,,,¶,2

^* Massey Cancer Center, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298; Department of Pathology, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298; Department of Human Genetics, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298; Department of Pharmacology and Toxicology, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298; ^|| Aquatic Biotechnology and Environmental Lab, Warnell School of Forestry and Natural Resources, University of Georgia, Athens, Georgia 30602; and ^¶ Mount Desert Island Biological Laboratory, Old Bar Harbor Road, Salisbury Cove, Maine 04672

To whom requests for reprints should be addressed at ² Department of Pathology, 1101 East Marshall Street, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298. E-mail: sholt3{at}mcvh-vcu.edu

Telomerase plays a primary role in the maintenance of telomeres in immortal, germ, and tumor cells in humans but is lacking in most somatic cells and tissues. However, many species, including fish and inbred mice, express telomerase in most cells and tissues. Little is known about the expression of telomerase in aquatic species, although the importance of telomerase for longevity has been suggested. We compared telomerase activity and telomere lengths among a broad range of tissues from aquatic species and found telomerase at significant levels in both long- and short-lived aquatic species, suggesting constitutive telomerase expression has an alternative function. Telomere lengths in these aquatic species were comparable to those observed in normal human tissues and cell strains. Given that a host of aquatic species with short life spans have telomerase and a tremendous capacity to regenerate, we tested the hypothesis that telomerase upregulation is important for tissue regeneration. During regeneration, telomerase activity was upregulated and telomere lengths are maintained with the shortest telomeres being elongated, indicating the importance for maintaining telomere length and integrity during tissue regeneration. Thus, the expression of telomerase in aquatic animals is likely not related to longevity but to their ability to regenerate injured tissue.

Key Words: telomere • telomerase • stem cells • tissue regeneration • chaperones