Upregulation of Telomerase Function During Tissue Regeneration

Abstract

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.

Telomeres in Fishes

“…In recent years, many fish species have become promising vertebrate models in studies regarding the length of the telomeres and the expression of the telomerase during aging and tissue regeneration [Elmore et al, 2008;Anchelin et al, 2011]. Fluorescence in situ hybridization (FISH) with both conventional and peptide nucleic acid telomeric probes and primed in situ labeling with (TTAGGG) 7 / (CCCTAA) 7 primers made the identification of telomeric DNA sequences in the chromosomes of approximately 80 fish species representing distant taxonomic groups possible [e.g.…”

Genomic Distribution of Telomeric DNA Sequences – What Do We Learn from Fish About Telomere Evolution?

“…This is in contrast to humans where telomerase activity is absent in most somatic cells but present in embryonic stem cells and tumors (Hiyama and Hiyama, 2007). Although some authors presume that high expression of fish telomerase may be related to the longevity, comparative analysis of telomerase activity in the short-and long-lived fish species showed no positive relationship between telomerase activity and the fish longevity (Elmore et al, 2008). Instead, another hypothesis was suggested: retention of the telomerase in adult fish might be crucial to maintain their regenerative capacity.…”

“…The length of the telomeric DNA in fish studied to date varies from 2 kb to 15 kb (Chew et al, 2002, Elmore et al 2008 and is similar to that observed in normal human cells (Elmore et al, 2008). Furthermore, retention of the telomere length throughout the entire life has been demonstrated in zebrafish, but not in the medaka (Hatekeyama et al, 2008;Lund et al, 2009).…”

“…So far, the telomerase gene in fish has been shown to be expressed in most cells throughout the entire fish life (Elmore et al, 2008;Hartman et al, 2009;Lund et al, 2009). This is in contrast to humans where telomerase activity is absent in most somatic cells but present in embryonic stem cells and tumors (Hiyama and Hiyama, 2007).…”

“…To test this hypothesis, short fragments of the caudal fish tissue have been removed in medaka (Oryzias latipes), zebrafish (Danio rerio), and mummichog (Fundulus heteroclitus) specimens, and telomerase activities were assayed before and during the regeneration period. Telomerase was shown to be upregulated during the tissue regeneration, which suggested that telomerase is involved in the fish tissue regeneration after injury (Elmore et al, 2008).…”