Nottingham “Dollies” show that cloned sheep age normally

Scientists have discovered that cloned sheep age at the same rate as ordinary sheep. Research led by Professor Kevin Sinclair at the University of Nottingham assessed the health of a flock of 13 sheep, in the first study of long-term health in cloned animals. The flock included four Finn-Dorsets, Debbie, Denise, Dianna and Daisy, made from the same mammary gland cell line that produced Dolly the Sheep. The sheep were cloned in 2007 using Somatic Cell Nuclear Transfer (SCNT), the process used to clone Dolly, and are genetically identical to her.

Debbie, Denise, Dianna and Daisy - sheep cloned from the same cell line as Dolly the Sheep. Photo courtesy of The University of Nottingham.

Debbie, Denise, Dianna and Daisy – sheep cloned from the same cell line as Dolly the Sheep. Photo courtesy of The University of Nottingham.

The scientists assessed the sheep’s metabolic, cardiovascular and musculoskeletal health, and compared signs of ageing in the cloned sheep to that of younger clones and normal control sheep. At almost 9 years old the Nottingham “Dollies” are fairly elderly for sheep, which generally live for up to ten years. But despite their age, the cloned sheep’s blood glucose levels, insulin levels and blood pressure were all normal. There were no signs of degenerative joint disease apart from mild, and in one case moderate, osteoarthritis – which the scientists propose is part of the normal ageing process in sheep. The new research suggests that sheep cloned using SCNT age in the same way as ordinary sheep.

Dolly the Sheep was the first mammal to be cloned from an adult cell, using the process of Somatic Cell Nuclear Transfer. This proved that a fully developed adult cell could be reprogrammed to make it pluripotent, behaving like a cell from a newly fertilised embryo, which heralded the advent of stem cell therapy and regenerative medicine. Since Dolly, SCNT has been used on more than 20 species of mammal, including recently in human cells, and remains the most effective way to reprogram cells to a pluripotent state.

However, SCNT is very inefficient at producing healthy cloned animals; the rate of miscarriage, birth defects and infant deaths is high. In addition, there have been concerns that clones which survive into adulthood age prematurely. Famously, Dolly developed osteoarthritis at an early age, and was found to have shortened telomeres (the endcaps of chromosomes), which are thought to be linked to ageing.

The Nottingham study assessed the flock’s glucose and insulin levels, blood pressure, and musculoskeletal health, and found them to be normal in both cloned and control sheep. The average blood pressure was similar between clones and control sheep, and was within the normal range of pressures for older sheep. The sheep had no sign of metabolic syndromes associated with age such as diabetes, high blood pressure and obesity, and SCNT cloning appeared to have no effect on their cardiovascular systems.

The scientists also took X-rays of the sheep’s joints, and used Magnetic Resonance Imaging (MRI) to study their knee joints –the joint most affected by osteoarthritis in Dolly. None of the sheep were lame or required treatment, although some had mild osteoarthritis in one or two joints – a normal sign of ageing.

Despite their old age, the cloned sheep were in overall good health, suggesting that cloning animals through SCNT has no harmful long-term effects on health. This contradicts speculation that cloning was responsible for Dolly’s poor health in her later years, and that the ageing process is accelerated in clones.

Read the full research paper [Nature]

Written by Laura Allison