Conclusions

The study of telomere biology and telomere maintenance pathways has provided and will continue to provide a great deal of insight into the processes of replicative senescence, the relationship between cellular senescence and organismal aging, the genesis of cancer, and the regenerative potential of embryonic stem cells. Use of in vivo and in vitro avian systems to facilitate research in these fields can only add to our body of knowledge. With the 6.6X draft sequence of the chicken genome now available, the chicken is a much more powerful model.

Investigation of telomere maintenance pathways in the chicken and other birds establishes, among other things, that nonrenewable cells and tissues exhibit little or no telomerase activity accompanied by division-dependent telomere shortening; that embryonic cells and tissues as well as transformed cells exhibit high levels of telomerase; and that many telomere-associated genes are expressed differentially in pluripotent, differentiated and transformed cell systems, much as is seen in human systems. TERT and TR genes are transcribed in at least one telomerase-negative cell type, which suggests that the regulation of telomerase activity is more complex than merely switching the genes for telomerase enzyme components on and off. While telomere shortening profiles are unlikely to be the equivalent of rings on a tree for the determination of chronological age, comparisons of telomere status in pluripotent vs. differentiated, transformed vs. nontransformed and early passage vs. senescent cells are informative. Considerable work is necessary to fill in gaps, but the chicken model for telomere biology offers the opportunity to study a vertebrate system free from many of the issues inherent in the murine model. Chickens, therefore, have the potential to become the new ''lab rat'' for aging research.

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