Bad News for Dolly?
When it was announced that Dolly, the cloned sheep, was derived from an adult cell (Ref. 1), followers of the telomerase story—which in its simplest form says that telomeres shorten as a function of age—wondered about Dolly. Would her telomeres reflect her chronological age or the age of the cells from which she was derived? And if telomere length were more adult-like than child-like, what would that mean for Dolly? Would that portend a shortened life?
The answers to some of those questions are now available in a study published in the May 27 issue of Nature by the group at PPL Therapeutics (Midlothian, UK) and the Roslin Institute (Midlothian, UK). Paul Shiels and coworkers report that, indeed, Dolly has short telomeres for her age. Comparing the telomere length of age-matched control sheep with Dolly and two of her colleagues that were cloned instead from fetal and embryonic cells, the results were unequivocal. Dolly's telomeres were significantly shorter than sheep of her age, and than those of the sheep cloned from fetal cells.
An interesting side-light from this work says that it is possible to mitigate the effects of aging on telomeres by restricting the amount of time the donor cells are cultured prior to nuclear transfer. (Recall that a key to the success for cloning Dolly was the culture in vitro of the mammary epithelial cells, during which some "reactivation" of the genome was believed to occur.) The cloned sheep with telomeres closest in size to age-matched control sheep was derived from cells that were held only briefly in culture.
What this result means in terms of Dolly's future, however, remains unclear. Because of what the researchers noted was a large size distribution in the mean telomere length in sheep, they can't tell whether Dolly and her peers will reach the critical telomere length in their lifetimes. The authors further note that both Dolly and Cumulina, the mouse cloned from adult cells, appear perfectly healthy, having even produced multiple offspring.
References
- Wilmut, I, Schnieke, A.E., McWhir, J., Kind, A.J., and Campbell, K.H., "Viable offspring derived from fetal and adult mammalian cells," Nature 385:810-813, 1997.
For more information: Paul Shiels, PPL Therapeutics, Roslin, Edinburgh EH25 9PP, UK. Tel: +44 131-440-4777. Fax: +44 131-440-4888. Email: pshiels@ppl-therapeutics.com.
By Laura DeFrancesco