A fascinating thing about DNA replication is that the actual process lacks the ability to replicate the very ends of chromosomes. That means chromosomes should get shorter with every round of cell division (DNA replication), but they remain more or less the same length, getting gradually shorter with aging. The natural shortening of chromosomes is refered to as cellular aging. So how do chromosomes maintain their ends if not by replication?

The answer, which earned the 2009 Nobel Prize in Physiology or Medicine, is telomeres and the enzyme Telomerase. Telomeres are short repeats of DNA found only at the ends of chromosomes. Think of them like plastic bits on your shoelaces that keeps them from unraveling. The function of the telomeres is to provide a template for the enzyme Telomerase to act. Telomerase, a complex made up of RNA and proteins, recognizes those repeats and can add more repeats when needed.

Scientists have been teasing apart how this happens for years. The current models rests with a complex of proteins that is not Telomerase, which is bound to the repeating sequence of the telomeres. The more repeats the more proteins (see the green blogs on the DNA in the top part of the figure, citation below). A large number of these protein complexes blocks Telomerase (right side of figure) from adding any more repeats, but when chromosomes become shortened, the lower number of protein complexes (bottom of figure) allows Telomerase to add more repeats.

The most recent and exciting news in this story was just published. It deals with the observation that telomere lengths differ in people of the same age. Although there is certainly an environmental affect on telomere length, it’s also clear there are strong genetic components to their maintenance. So what are they? Are there specific gene variants that allow more efficient telomere protection than others? Are certain diseases associated with those genetic variants as a result of inadequate telomere protection?

In this genetic association study (citation below), the researchers attempted to uncover genetic variants which are associated with telomere length. They found a specific variant (allele) associated with the gene TERC. Take a look at the figure, TERC is that big loop of RNA in the Telomerase enzyme. It turns out having two copies of the inefficient allele makes ones DNA look 8 years “older” than it actually is. What that means in terms of how you look, or your health is still to be discovered. However, it is already significant that the genetic basis underlying natural differences in telomere lengths (i.e. cellular aging) have begun to be described.

Image:

Shore, D., & Bianchi, A. (2009). Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase The EMBO Journal, 28 (16), 2309-2322 DOI: 10.1038/emboj.2009.195

Citation:

Codd, V., Mangino, M., van der Harst, P., Braund, P., Kaiser, M., Beveridge, A., Rafelt, S., Moore, J., Nelson, C., Soranzo, N., Zhai, G., Valdes, A., Blackburn, H., Leach, I., de Boer, R., Goodall, A., Ouwehand, W., van Veldhuisen, D., van Gilst, W., Navis, G., Burton, P., Tobin, M., Hall, A., Thompson, J., Spector, T., & Samani, N. (2010). Common variants near TERC are associated with mean telomere length Nature Genetics DOI: 10.1038/ng.532