New clues to achieving eternal life
1 April 2010
Researchers at Umeå University in Sweden have shown that cells that
grow forever get this capacity through gradual changes in the expression
of genes that govern the repair of DNA damage and regulate growth and
The research also shows that activation of the enzyme complex
telomerase, which is necessary for unlimited growth, occurs late in
The study, published in the April issue of the journal Aging
Cell, was performed by a research team directed by Professor Göran
Roos at the Department of Medical Bioscience, Pathology. The study
how cells’ telomers (repetitive DNA sequences on the ends of
chromosomes) are regulated during the process that leads to eternal
life of cells.
One type of blood cells, lymphocytes, were analyzed on repeated
occasions during their cultivation in an incubator until they
achieved the ability to grow an unlimited number of cell divisions,
a process that is termed immortalization. In experiments,
immortalization can be achieved following genetic manipulation of
cells in various ways, but in the lymphocytes under study this
occurred spontaneously. This is an unusual phenomenon that can be
likened to the development of leukemia in humans, for example.
The ends of chromosomes, the telomers, are important for the
genetic stability of our cells. In normal cells telomers are
shortened with every cell division, and at a certain short telomer
length they stop dividing. With the occurrence of genetic mutations
the cells can continue to grow even though their telomers continue
to be shortened.
At a crticially short telomer length, however, a so-called crisis
occurs, with imbalance in the genes and massive cell death. In rare
cases the cells survive this crisis and become immortalized. In
previous studies this transition from crisis to eternal life has
been associated with the activation of telomerase, an enzyme complex
that can lengthen cells’ telomers and help stabilize the genes. A
typical finding is also that cancer cells have active telomerase.
The current study shows that cells initially lose telomer length
with each cell division, as expected, and after a while enter a
crisis stage with massive cell death. Those cells that survive the
crisis and become immortalized evince no activation of telomerase;
instead, this happens later in the process.
The Umeå researchers
found that the expression of genes that inhibit telomerase is
reduced in cells that get through the crisis, but telomerase was not
activated until positively regulating factors were activated, thus
allowing the telomers to become stabilized through lengthening. By
analyzing the genetic expressions the scientists were able to show
that the cells that survived the crisis stage had mutations in genes
that are key to the repair of DNA damage and the regulation of
growth and cell death.
This discovery provides new insights into the
series of events that needs to occur for cells to become
immortalized, and it will have an impact on future studies of
leukemia, for example.
The studies were carried out in collaboration with the Centre for
Oncology and Applied Pharmacology, University of Glasgow and the
Maria Skodowska-Curie Memorial Cancer Centre and Institute of
Degerman S, Siwicki JK, Osterman P, Lafferty-Whyte K, Nicol Keith
W, Roos G: Telomerase upregulation is a postcrisis event during
senescence bypass and immortalization of two Nijmegen breakage
syndrome T cell cultures. Published at:
Printed edition: Aging Cell. 2010; 9 (2): 220-2358.