Swedish study links telomeres and ageing
EU-funded researchers in Sweden have shown that the shortening of telomeres, the protective structures at the end of chromosomes, as people age varies between individuals and depends on the telomeres' original length. Although prior population studies have indicated that telomeres might be used to predict lifespan, the new research shows that the process is in fact much more complicated than had previously been assumed.
The study, published in the journal PLoS Genetics, was partly supported through the TELOMARKER ('Identification and characterisation of novel human telomere-related biomarkers that aid cancer management by improving patient diagnosis, treatment selection, response monitoring, and drug development') project, financed with EUR 2.8 million under the 'Health Theme' of the EU's Seventh Framework Programme (FP7).
One of the researchers who discovered telomeres in the 1970s, Elizabeth Blackburn, likened the DNA-rich, protective end-structures of our chromosomes to the 'tips on the ends of shoelaces that keep them from unravelling'. Telomeres contain important genetic information and provide stability that protects against the chromosome rearranging, which can lead to cancer.
When the cell divides, the telomeres are destroyed before being restored by an enzyme called 'telomerase reverse transcriptase'. However, this enzyme does not replace the entire length of the telomere, so the structure gets shorter every time the cell divides. When the telomeres in a normal cell have disappeared completely, the cell is destroyed. Many cancers are a result of 'immortal cells' that survive telomere loss.
Past studies of telomeres have shown that people with smoking-associated cancers have shorter telomeres compared to healthy controls. This has led to speculation that, on a population level, shorter telomeres may predispose individuals to certain cancers. However, evidence of individual telomere-shortening rates and the possible relationship with cancers has been lacking.
In the current study, researchers led by Professor Göran Roos at the University of Umeå investigated the shortening of telomeres in 959 individuals who had donated blood samples at 9- to 11-year intervals. Some of the individuals had developed tumours over the decade between donations. The scientists were surprised to find that while the shortening rate was strongly correlated with the initial length of the telomeres, it was not related to later tumour development.
The group studied did in fact show the expected decline in telomere length over time, but the researchers also saw large differences between individuals. In roughly a third of the subjects, the telomeres actually lengthened over the study period. However, according to the study, 'those with the longest telomeres at the first blood draw demonstrated the most pronounced telomere shortening over time, and vice versa.'
The results indicate that the telomere-maintenance machinery protects the shortest telomeres. However, other factors are likely to influence the rate of shortening as well. Telomere length at first blood draw could only explain 57% of the variation in the rate of shortening; 43% remains to be accounted for, and may well include lifestyle factors, oxidative stress or inflammation.
'Abnormal telomere length in blood cells has been reported with cancer patients,' the study reads, 'but in this material - which includes 314 individuals diagnosed with malignant tumours after the second blood sample - there was no association between telomere length and later cancer diagnosis.' However, they did show some relationship between prostate cancer and short telomere length nine years before diagnosis; a finding that merits further investigation.
Contrary to the notion that telomere length at a certain age can predict a theoretical future lifespan, the new findings show that regulation of telomere length throughout life is more complex than had previously been believed. Importantly, the authors suggest that 'it might well be possible to avoid excessive telomere loss by living a healthy life'.
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Category: Project results
Data Source Provider: Swedish Research Council; PLoS Genetics
Document Reference: Nordfjäll K., et al. (2009) The individual blood cell telomere attrition rate is telomere length dependent. PLoS Genet 5(2): e1000375. Published online 13 February; doi:10.1371/journal.pgen.1000375
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