Roslin,
SCOTLAND- (5/27/99)- When Dolly, the first mammal cloned from an adult
cell, was born, many researchers wondered what the effects of starting life
with 'old' cells might be. The scientists who cloned Dolly now report that
the famous sheep's DNA might be showing its age.
Telomeres are segments of DNA found at the tip of each chromosome in nonbacterial
cells. Replication of telomeres is regulated by a special enzyme called telomerase.
As organisms age, the telomeres tend to shrink in size. Dolly was cloned from
cells derived from the udder of a six-year old Finn Dorset ewe. The Scottish
researchers who first cloned Dolly compared her telomeres with those of age-matched
controls, and with the telomeres of two sheep clones, one of which was derived
from embryo cells and the other of which was cloned from fetal fibroblasts
The researchers used restriction enzymes to measure the mean sizes of terminal
telomere fragments for all of the animals in the study.
The results from the control sheep confirmed that the telomeres do indeed
decrease in size with age. The researchers also observed that the telomeres
were shorter in all of the clones compared with the normal animals. The difference
in size achieved statistical significance for the animal cloned from mature
cells (Dolly) and the animal cloned from embryo cells. The telomeres from
the clone produced from fetal fibroblasts were shorter, but not enough to
be considered statistically significant.
The telomeres derived from Dolly were the length that would be expected for
the age of the original donor cell. Dolly, now two years and counting, was
derived from six-year old parent cells. The telomeres from the clone derived
from embryonic cells also appeared to reflect the age of the original cells,
as well as their time in culture. The fetal fibroblasts used to clone the
other animal had spent only a minimal time in culture.
"These observations indicate that the extent of shortening of terminal
restriction fragments might be mitigated, principally by minimizing duration
in culture and by careful choice of source of donor cells," noted Dr.
Paul Shiels, part of the original team that cloned Dolly.
It is likely that these differences in telomere length can be explained on
the basis of the different ages of the cells used to clone the different animals,
he noted. However, the sample size was small and the possibility that these
differences reflect only normal variations in telomere length cannot be excluded.
The researchers don't know whether or not the telomere changes reflect changes
in the physiological ages of the animals. It may be that the effect on telomeres
may have no effect on the longevity of cloned animals. Veterinary examinations
indicate the animals are happy and healthy. Dolly herself has produced two
litters of lambs. Other researchers have cloned mice from mice clones and
report no apparent effects on longevity in those animals.
Telomeres are believed to act as a protective cap on on chromosomes. With
each round of DNA replication that occurs when a cell divides, a little bit
of the telomere wears away. Current research suggests that once a cell has
replicated a certain number of times, the telomere degrades to such a point
that the cell commits suicide.
Telomere research is gaining momentum on several fronts. Many laboratories
are investigating the role of telomeres in aging and death. Cancer researchers
are also very interested in telomeres. Many cancer cells appear to owe their
immortality to a switched on telomerase gene.
The research appears in the May 27 1999 issue of the journal Nature.
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