When It Comes to Aging, Size Matters

Recently, the Nobel Prize in Physiology or Medicine was awarded to three scientists who defined the role and functionality of an enzyme important to the aging process. They outlined just how chromosomes — those vital, thread-like molecules of DNA that contain our genes — are protected against being destroyed. It turns out that a telomere exists on the end of each chromosome, and the longer the telomere, the longer the life of the cell.

Without telomeres, chromosomes are damaged each time they replicate and divide. Each replication would lead to shorter and shorter DNA, eroding the genetic material and damaging the chromosome. However, telomeres protect the end of the chromosome, allowing the entire length to be replicated, without losing precious genetic codes. Telomeres contain a unique, repeated, DNA sequence that functions like a little cap on the end of each chromosome. Telomeres are formed by an enzyme called telomerase. Telomerase extends the DNA of the telomere, thus providing even more protection for the delicate ends of the strands of DNA. Therefore, if telomerase activity is high, telomere length is maintained and chromosomes are protected and continue to live productive, healthy lives, as cells go. If, however, telomerase activity is low, the telomeres are shortened and the cells are not protected, leading to cellular aging and cell death. And more cell death leads to more overall aging, and reduced life expectancy.

Since the 1930s, scientists have known about the existence of telomeres, but only recently have they understood the role these structures may play in the course of natural aging or disease processes. Cancer cells, for instance, have increased telomerase activity, guaranteeing near-eternal life for cancer cells. Telomerase defects, on the other hand, lead to inherited diseases, such as types of anemia, and diseases of the skin and cardiovascular system, since cells age and die before they can sufficiently reproduce. Now that scientists understand the role of telomeres in natural aging, as well as disease, telomerase is a new target for therapeutic development. A telomerase antagonist was recently studied in human glioblastoma and revealed promising results. Also, numerous cardiovascular risk factors are associated with telomere length, exposing the possibility of protective therapies in the future.

Even before their role was completely understood, telomeres were markers of human aging and stress. To some extent, telomere length is genetically predetermined at birth. Telomerase activity and telomere length, however, are influenced by a variety of factors, including environmental exposures, oxidative stress, and, to some extent, lifestyle. The Nobel Laureates, who have spent their careers studying telomeres and telomerase activity, report that simply reducing stress can help to lengthen telomeres and delay cellular aging, prolonging overall life. Telomeres might be a more important indicator of longevity, equating to a biological age, rather than a chronological one. So, relax, lengthen those telomeres and enjoy a long life!

References

Bize, P., Criscuolo, F., Metcalfe, N., Nasir, L., & Monaghan, P. (2009). Telomere dynamics rather than age predict life expectancy in the wild Proceedings of the Royal Society B: Biological Sciences, 276 (1662), 1679-1683 DOI: 10.1098/rspb.2008.1817

Das, B., Saini, D., & Seshadri, M. (2009). Telomere Length in Human Adults and High Level Natural Background Radiation PLoS ONE, 4 (12) DOI: 10.1371/journal.pone.0008440

Huzen, J. (2010). The emerging role of telomere biology in cardiovascular disease Frontiers in Bioscience, 15 (1) DOI: 10.2741/3604

Marian, C., Cho, S., Mcellin, B., Maher, E., Hatanpaa, K., Madden, C., Mickey, B., Wright, W., Shay, J., & Bachoo, R. (2010). The Telomerase Antagonist, Imetelstat, Efficiently Targets Glioblastoma Tumor-Initiating Cells Leading to Decreased Proliferation and Tumor Growth Clinical Cancer Research, 16 (1), 154-163 DOI: 10.1158/1078-0432.CCR-09-2850

Nobel Assembly at Karolinska Institutet (15 October 2009). “The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak for the discovery of ‘how chromosomes are protected by telomeres and the enzyme telomerase.’” Press release.