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9 February 2012
To the Editor
Margaret McCartney in BMJ 2012;344:e681 provides a stimulating observational piece on telomere testing as a means of assessing biological age and its implications for personal health. She notes that telomere length measurement “raises more questions than it answers”. This is indeed so and telomere length measurements may not answer many personal health questions at all well.
Human ageing is a complex and gradual process and suitable molecular markers to dissect this are lacking. Determination of personal health status based on a biomarker of ageing and not as a direct function of chronology requires very sensitive and specific biomarkers. As an experienced researcher in this field, I know that this process is not straightforward.
Biological age constitutes ageing at the level of the cell/tissue/organ and organism. Validated markers of biological age are few and must be able to fulfill the condition of the Baker and Sprott criterion, namely; ‘‘A Biomarker of Aging (BoA) is a biological parameter of an organism that either alone or in some multivariate composite will, in the absence of disease, better predict functional capability at some late age, than will chronological age’’ (1).
While a host of biomarkers have been tested, only two markers have been identified that may fulfil this criterion; these comprise CDKN2A and telomere length. CDKN2A has only been tested in in a number of small independent studies and rarely in combination with telomere length (4). In these, telomere length has proven to be a significantly weaker biomarker (2). CDKN2A has proven superior to both telomere length and chronological age (2,3). Furthermore, inter-individual variation in telomere length is subject to numerous socio-economic and lifestyle confounders (5) as well as numerous methodological issues (4). This makes its use when applied to individuals very unreliable.
From this standpoint, using telomere length commercially for determining the health status of any individual seems premature. Its use is much more suited to large clinical, or laboratory studies of ageing disease. A knowledge of telomere length as a read-out of health is, however, still very relevant, but only if this can be applied in the context of population or public health, when socio-economic, lifestyle and epigenetic confounders are addressed (5,6).
It remains to be determined how relevant CDKN2A expression will prove to be both as a measure of personal and public health.
1. Baker GT 3rd, Sprott RL. Biomarkers of aging.
Exp Gerontol. 1988;23:223-39
2. Koppelstaetter C, et al. Aging Cell. 2008; 7:491-7.
3. McGlynn LM, et al Shiels PG. Aging Cell 2009; 8:45-51
4. Shiels PG. J Gerontol. 2010 65(8):789-91
5. Shiels PG et al. PLoS One 2011; 6(7):e22521
6. Mc Guinness D. et al Shiels PG. Int J Epidemiol. 2012;
Jan25. [Epub ahead of print]
Competing interests: None declared
Institute of Cancer Sciences, University of Glasgow, Level 2, McGregor Building, Western Infirmary Glasgow
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