Understanding the reasons for variations in telomere length may provide new insights into successful ageing
Dr Carmen Martin-Ruiz introduces Telomeres
See more on the MRC comms Youtube channel
What is telomere length?
A telomere is a region of repetitive DNA at the end of a chromosome which protects it from destruction. If cells divided without telomeres, they would lose the end of their chromosomes and the necessary information they contain. The telomere is a disposable buffer which is consumed during division of somatic cells. Thus, while the existence of telomeres means that cells can divide and carry a full compliment of DNA, it also means that somatic cells age – they cannot divide for ever.
Why study telomere length?
Telomere length may be a useful index of biological age. The biological age of an individual can be different from the number of years lived. Individuals may be biologically ‘younger’ or ‘older’ than their years if their bodies are ageing slower or faster than average. A marker for biological age integrates measures of general health, frailty, capability and wellbeing and is thus an indicator of the probability of survival.
What we know and what we don’t know
Some studies have found that shorter telomeres are associated with mortality, morbidity, lower socioeconomic position, gender, menopausal status, smoking, obesity, insulin resistance, vitamin D and inflammation however, not all results are consistent.
Further, there are almost no data examining changes in telomere length with age in the same individuals. This is because almost all studies so far have been single ‘snap-shots’ and have had no follow ups.
What is new about this study?
Size matters! Ageing is such a complex and multifaceted process that many factors contribute to variation in biological age and telomere length. We need to look at large numbers of people, and very large volumes of well characterised information. The HALCyon telomere work package with additional funding from an MRC project grant (both led by Professor Thomas von Zglinicki) has enabled the creation of one of the largest telomere datasets in the world (n~4900) of which a significant number are repeat measures (n~2600). Our study is unique in this respect, being the largest population-based telomere study so far. This has been made possible by the integration of various cohort studies and by important technical advances in the measurement of telomeres and statistical cross-validation.
For the first time, we have the possibility to measure individual change in telomere length over long periods of life in a large number of people. This provides much needed insight into the ageing process at the individual level.
What we are researching
Image courtesy Peter Lansdorp
We have examined:
- the methodological limitations of using telomere length as a biomarker of ageing (and how to overcome these limitations as much as possible)
- the association between gender and telomere length, by conducting a systematic review of published studies and performing meta-analyses which included HALCyon studies and all others studies worldwide identified as having relevant data
- whether telomere length or its change with age are consistently associated with subsequent physical capability across the HALCyon cohorts (with WP1)
- patterns of longitudinal change in telomere length and cohort differences in these patterns
- inter-lab comparisons to assess the impact on telomere length measures of differences in the methodology employed by different laboratories
- polymorphisms in TERT, BRUNOL4/ VPS34, TERC and TERF1 and their associations with telomere length and rate of telomere length change in the HALCyon cohorts.
What have we found so far?
- Although assessment of telomere length is used diagnostically in some well defined clinical areas, the use of telomere length to aid diagnosis or risk assessment in the general population is premature (von Zglinicki., British Medical Journal 2012).
- In the four HALCyon cohorts with relevant data there was very little evidence of associations of telomere length with physical capability (Gardner et al., PLoS One 2013)
Please see the Case for Support for a detailed, more technical overview of the work packages.
Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y (Eds). A life course approach to healthy ageing. Oxford University Press to be published January 9th 2014.
- Chapter 13: A life course approach to biomarkers of ageing
Dr Carmen Martin-Ruiz and Professor Thomas von Zglinicki