Cloning by nuclear transfer (NT) of adult somatic nuclei into enucleated oocytes involves epigenetic reprogramming to allow the expression of gene programmes appropriate for early development. One of the key questions is whether cellular ageing is reset during reprogramming. It certainly seems to be, at least at the organismal level, given the reports of a relatively normal lifespan for many animals cloned by somatic cell NT. Previous reports have suggested that cattle fetuses cloned from cultured donor cells at, or near, senescence grow into healthy calves and yield fibroblasts with extended lifespans and telomere length relative to cells from age-matched control fetuses. Now, John Clark and colleagues revisit this crucial question by carrying out nuclear-transfer experiments in sheep, using cell lines with a range of proliferative capacities. Remarkably, primary cell lines derived from cloned progeny invariably had the same proliferative capacity as the donor cell lines. Furthermore, the actual age of the donor nucleus does not seem to alter the lifespan of the NT clone-derived cell lines.

To assess the rate with which the cloned cells age, the authors turned to the telomeres because they are eroded as the cell divides and, unless replenished, are thought to contribute to cellular senescence once they reach a crucial length. Based on the inverse correlation between telomere erosion rates and proliferative vigour of the cell lines the authors suggest that the rate of telomere shortening determines lifespan.

Importantly, the rates of telomere erosion of the lines derived after NT cloning closely matched those of the parental cultures. These data are consistent with previous reports from cattle, in that telomeres from donor cells near senescence are extended upon NT; however, they do not reproduce the claim that bovine telomeres are extended upon cloning relative to non-cloned controls. These data are also consistent with a previous claim that the first cloned sheep, Dolly, had shorter telomeres than control animals of the same age. Evidently, cellular senescence also correlates with telomere shortening in animals cloned by NT. Indeed, the rate of telomere erosion might determine the lifespan of both donor and cloned sheep fibroblasts.

The authors conclude that proliferative capacity and rates of telomere erosion are conserved during nuclear transfer, and are therefore likely to be a genetically determined property in sheep. A crucial question that remains unanswered is whether there is any effect on overall organismal ageing or pathologies such as cancer. How and if replicative senescence and telomere biology are related to ageing remains an important frontier for future investigation.