25 November 2013
ByAppeared in BioNews 732
End to End: Telomeres and Ageing
Organised by Imperial College London
Presented by Dr Elizabeth Blackburn
Great Hall, Sherfield Building, South Kensington Campus, Imperial College London, Exhibition Road, London SW7 2AZ
Wednesday 13 November 2013
The 2013 Schrödinger Lecture at Imperial College London was delivered by Dr Elizabeth Blackburn, an Australian-American biologist based in California. The talk titled 'End to End: Telomeres and Ageing' was an exciting and colourful précis of her work on the mechanisms of ageing. She won the Nobel prize for Physiology or Medicine in 2009 for her work investigating the fundamental, microscopic workings of our own mortality, sharing it with Carol Greider and Jack Szostak.
Dr Blackburn introduced her Schrödinger lecture in homage to the eponymous physicist whose lecture series 'What is Life?' bridged scientific disciplines in its attempt to explain the mechanisms of life with physics and chemistry.
It was a work that was very influential for Crick and Watson, the biologists who first discovered the helical structure of DNA. Schrödinger's endeavour to tackle biological questions with more deductive and quantitative methods seems more prescient than ever, Blackburn's cutting edge research indeed takes place at this frontier.
A telomere is a repetitive sequence of nucleotides (the organic units of DNA) at the end of each arm, or chromatid, of our chromosomes. Our bodies are sustained by constant cell regeneration - however, the replication machinery that copies strands of our DNA doesn't work at the very ends of our chromosomes.
Telomeres serve as a protective cap that can be worn away during cell division, like a replication burning candle wick, without the loss of key genetic information. When our telomeres get too short our cells undergo senescence, changes to molecular structure that disrupt functionality. 'Uncapped' chromosomes quite literally get the jitters and can be seen to dance madly around under the microscope. Dr Blackburn was the first to identify this genomic instability as a key mechanism behind ageing and it led her to find solace in the unlikeliest of places - pond scum.
A small protozoa found in pond scum called tetrahymena thermophila was found to contain an enzyme, telomerase, that could replenish telomeres. Dr Blackburn established this unequivocally by mutating the telomerase gene in the tetrahymena and showing that this caused cell malfunction. While normal human cells have little or no telomerase, stem cells were found to have high levels. Cancer cells, which have very high telomerase activity, are thought to achieve immortality in this way. It has since been established that telomerase defects are behind some inherited diseases, such as congenital aplastic anaemia, where stem cells in the bone marrow do not replicate sufficiently.
However, the regulation of telomerase in our cells is very complex and just one piece of the puzzle in understanding the shortening of telomeres and the onset of ageing. In order to untangle this problem and quantify her findings, Dr Blackburn turned to statistical analysis of large data sets, in order to get a 'bird's-eye view' of the problem. Telomere length was sampled extensively in diverse populations, from around 100,000 people in total. She found that while in the population as a whole there was huge scatter in telomere length, by taking tranches of data (divided by age, gender or race for example) some very intriguing trends emerged, revealing genetic and non-genetic associations.
She saw that menopausal women's telomeres stayed longer than men's and that centenarians had particularly long telomeres throughout their lives. However it was the environmental and behavioural correlations that were particularly thought-provoking; smokers were found to have shorter telomeres than non-smokers and educational attainment was associated with long telomeres.
Strikingly, stress levels were shown to have an impact on telomere length, with years of chronic psychological stress causing cumulative telomere attrition, bringing a whole new meaning to 'burning the candle at both ends'.
Dr Blackburn was quick to point out that such studies are 'soft' in the sense that participants' results are always subjective but the statistics were persuasive. Questioners later pushed Dr Blackburn to speculate on these trends, the link with education in particular, however she was tentative in her answers, emphasising it was only the data that we could be sure of and from which our conclusions must be drawn.
As an ageing population heralds increased rates of disease as well societal problems, understanding the physiology of our ageing is of vital importance. Dr Blackburn's research has uncovered a new mechanism underlying ageing and her latest large population study has great statistical power.
Identifying genetic links with telomere shortening gives us the potential to pre-empt medical treatment, and understanding non-genetic links may help us guide social policy.
After the lecture guests were invited to meet with current researchers in the field like Dr Jess Buxton and free knitting patterns for the delightful knitted chromosomes designed by Marion Crick were also available - a playful use of wool as strands of DNA. Dr Blackburn even took one home with her.