BIOTECHNOLOGY
IMMORTALITY IN TWO STEPS
Becoming immortal may be more difficult than previously thought, at least for cancer cells. Scientists have long theorised that cancer cells, which never age, have achieved their immortality by turning on the production of an enzyme called telomerase in cells that don’t normally produce it. Telomerase has long been known to play
an important role in ageing as it lengthens the protective caps, or telomeres, on the
ends of chromosomes – which wear away during each cell division in healthy cells (see Life extending lace caps p29). However, a new study by researchers at
the University of California, Berkeley, and at the University of California, San Francisco, suggests that this process of immortalisation is more complicated - and in fact occurs in two distinct steps (Science, doi: 10.1126/ science.aao0535).
The team studied the process using
genome engineered cells in culture, and also tracked skin cells as they progressed from a mole into a malignant melanoma. The results showed that immortalisation is triggered initially by a mutation in the ‘promoter’ region upstream of the telomerase gene that regulates how much of the enzyme is produced.
In the initial phase, they observed that the mutation does not prevent bulk telomere shortening, but extends cellular lifespan by healing the shortest telomeres. In the second phase, the critically short telomeres lead to genome instability and more telomerase is produced to sustain cell proliferation. ‘Our findings have implications for how
to think about the earliest processes that drive cancer and telomerase as a therapeutic target,’ said UC Berkeley assistant professor Dirk Hockemeyer. ‘It also means that the role of telomere biology at a very early stage of cancer development is vastly under- appreciated.’ If the group’s findings are replicated in other cancers, he suggests that this ‘would warrant that people look more carefully at the role of early telomere shortening as a tumour suppressing mechanism for cancer’. Roughly 90% of all malignant tumours
use telomerase to achieve immortality. While only 10-20% have this mutation in the promoter region upstream of the telomerase gene, they include 70% of all melanomas and 50% of all liver and bladder cancers. The discovery of telomerase and its
role in replenishing the caps on the ends of chromosomes, by Elizabeth Blackburn and Carol Greider at UC Berkeley and John Szostak at Harvard University in the 1980s, earned them a Nobel Prize in Physiology or Medicine in 2009. Work is currently under way to develop various cancer therapies aimed at turning down the production of telomerase in tumours.
Los Angeles (UCLA). The ‘clock’, which is based on 353 methylated cytosine bases in DNA, predicts a person’s age from a blood sample with an accuracy of one to three years, he pointed out – a fact that suggests it relates to the underlying process that causes ageing. Changes in DNA methylation are
responsible for switching genes on or off. They occur in response to both extrinsic and intrinsic environmental and lifestyle factors like what we eat
or how polluted the air is, or how much exercise we take. So could these shifting epigenetic patterns also determine how fast we age? New insights into the mechanisms of ageing are also changing the way
we define ageing, according to Kibar. We now know that it is not only different individual people that age differently, he says, but ‘advances in science allow us to define metabolic age and more refined types of ageing, while even different organs and body tissues age differently’. Interestingly, David points outs
that Horvath’s ageing clock ticks faster before the age of around 20, whereupon it slows down - possibly
30 08 | 2017
HEITI PAVES/SCIENCE PHOTO LIBRARY
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