Abstract. Dolly, the first mammal cloned from a somatic cell, had shorter telomeres than age-matched controls and died at an early age because of disease. To investigate longevity and lifetime performance in cloned animals, we produced cloned cows with short telomeres using oviductal epithelial cells as donor cells. At 5 years of age, despite the presence of short telomeres, all cloned cows delivered multiple healthy offspring following artificial insemination with conventionally processed spermatozoa from noncloned bulls, and their milk production was comparable to that of donor cows. Moreover, this study revealed that the offspring had normal-length telomeres in their leukocytes and major organs. Thus, cloned animals have normal functional germ lines, and therefore germ line function can completely restore telomere lengths in clone gametes by telomerase activity, resulting in healthy offspring with normal-length telomeres. Key words: Aging, Cattle, Mammalian cloning, Germ line, Telomere (J. Reprod. Dev. 57: [636][637][638][639][640][641][642] 2011) n mammals, most somatic cells undergo a finite number of cell divisions and ultimately enter a nondividing state known as replicative senescence [1] as a consequence of structural changes that take place in chromosomes over time. Chromosomes terminate in a nucleoprotein complex termed a telomere, which consists of repetitive sequences of G-rich noncoding DNA (TTAGGG)n and specific proteins. Telomeres are attached to the nuclear matrix and protect chromosome ends from degradation, fusion and recombination [2]. However, conventional DNA polymerases cannot replicate the extreme 5' ends of chromosomes because removal of the most terminal RNA primer in the lagging strand leaves a small region of uncopied DNA; therefore, telomeres are incrementally eroded with each cell division [3]. On the basis of this mechanism, it has been proposed that progressive telomere shortening during each cell division eventually yields a threshold telomere length beyond which additional normal cell divisions are not possible. Thus, telomere length acts as a mitotic clock that accounts for the limited lifespan of cells [4].In recent years, animal production by somatic cell nucleus transfer (SCNT) has offered a range of opportunities in basic and applied research, agriculture, genetic conservation and human medicine [5]. Somatic cell-cloned animals are produced using donor cells that have variably aged in vivo and in vitro, raising interesting questions about possible foreshortening effects on the lifespan and reproductive potential of these animals. In some cases, particularly with respect to cows and sheep, there is also the question of potential reductions in overall milk production. In this context, the telomere lengths in Dolly, the first mammal produced by SCNT, have been reported to be significantly shorter than those in age-matched controls, and this was consistent with the age of the donor mammary epithelial cell culture, which was derived from a 6-year-old donor sheep [6]. Dolly di...