Probing the fountain of youth

The key to predicting longevity seems to lurk in X-chromosome endings. Thank you, mother

By Owen Dyer

The mystery of inherited longevity appears to be one step closer to being solved. Research published in the February 14 issue of The Lancet, suggests that a crucial gene resides on the X-chromosome. That could mean that, in men, any inherited tendency to age faster or slower depends exclusively on genes derived from the mother. The father only comes into the picture when predicting women's rate of ageing.

The research hangs on the premise, now fairly widely accepted, that there is a correlation between ageing and the progressive shortening of telomeres, the strands of repetitive DNA that lie at both ends of every chromosome.

It's been known for some time that telomeres serve a protective purpose, rather like the plastic ends on shoelaces which prevent them from unravelling. But with each cell division, the length of telomeres shortens, until eventually the genetic material at the heart of the chromosome is exposed to decay, leading to cell senescence. Moreover, the shortened chromosome ends become 'sticky' and promote chromosome rearrangements. Some rearrangements may contribute to the development of cancers.

The researchers, from the University of Leuven in Belgium, measured terminal restriction fragment (TRF) length in white-blood-cell DNA taken from individuals from the family-based cohort of the Flemish Study on Environment, Genes, and Health Outcomes.

It was already known that twins generally have similar telomere lengths. This study found that the same is true of singleton siblings. Unsurprisingly, there was no correlation of telomere length between spouses. But the important findings concern the genetic relationships between parents and children.

Mothers' telomere lengths were closely correlated to sons and daughters. On the other hand, fathers' telomeres appeared to have no bearing on those of their sons, yet showed a clear correlation to those of their daughters. The statistical power of the survey leaves little room for doubt in these findings. The obvious explanation is that a gene for telomere length resides on the X-chromosome.

"We identified a possible genetic mechanism that interferes with longevity and the potential of ageing, " said study author Dr Jan Staessen. "We think it's an X-linked phenomenon. " The exact location of the gene has not been determined but Dr Staessen and his colleagues believe they have identified a likely candidate.

One day in the not too distant future, the question of longevity genes is likely to become somewhat less academic than it is

at the moment. If the era of designer babies is approaching, changes to longevity genes are bound to be near the top of many parents' shopping lists.

In the meantime, there may be other ways to influence telomere length even in those who lack the best genes. The shortening of telomeres can be dramatically delayed in the presence of the enzyme telomerase, whose action is still poorly understood. It may be that to reach an age of three score and 10 will be considered no great achievement for our grandchildren's generation.