A Belgian study into the inheritance of telomere length published in The Lancet this week proposes that ageing may be an X-linked trait. Telomeres, specialised DNA sequences at the end of chromosomes, act as ‘caps’ to protect and stabilise the chromosome ends during replication. Human telomeres comprise tandem repeats of the sequence TTAGGG, and the overall telomere length (typically 15,000 base pairs at birth) decreases during every cycle of cellular replication, losing 25-200 base pairs per cell division. Eventually, once its telomeres have become critically short, the cell becomes senescent, and eventually dies. Previous research has suggested that telomere shortening and cellular senescence may be directly linked to the ageing process, and that shorter telomeres are associated with increased incidence of disease and risk of mortality. Twin studies have indicated that telomere length may be inherited. This study [Nawrot TS et al. (2004) Lancet 363, 507-510] reports findings on the inheritance of telomere length.
The length of a terminal fragment of chromosomal DNA from white blood cells was determined for subjects from families, including 128 parents and 199 offspring. A normal distribution of telomere length was observed, with age having the most significant influence on length, although a smaller effect was noted for gender (men tending to have shorter telomeres than women of the same age) and for smoking, with a shorter sex and age adjusted terminal fragment length observed for smokers than for non-smokers. Correlations based on relationship were examined both with and without adjustment for gender, age and smoking status. In both cases, strong and significant correlations were observed between telomere length in father-daughter, mother-son and mother-daughter pairs, but not father-son (or spouse-spouse) pairs. The authors propose that the most plausible explanation for this correlation is an X-linked mechanism of inheritance for telomere length, and suggest candidate genes on the X-chromosome that may account for this.
Comment: This study provides sufficient evidence to warrant further investigation into the nature of inheritance of telomere length, which may also shed light on genetic factors that influence telomere length and ageing. A better understanding of the mechanisms that underlie the ageing process is potentially of enormous value to medicine with respect to age related diseases and conditions, and also to cancer. For example, telomerase (an enzyme that replaces the TTAGGG repeats lost during cell division and allows indefinite cellular reproduction without ageing) is absent from normal somatic (non-reproductive) cells but found in around 90% of human cancers.