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Australian researchers have made a discovery about telomeres that may have implications for aging, heart disease, cancer, and other age-related diseases.

So, what are telomeres? 

Each of the chromosomes that store our genetic information has a telomere at each end. This protective cap consists of a specific DNA sequence that is repeated thousands of times and has two purposes: firstly, it protects the coding regions of the chromosomes and prevents them from being damaged, and secondly, it acts as a clock that controls the number of replications a cell can undergo; this is thought to act as a quality control system to ensure that aged and potentially damaged cells do not remain in circulation.

Telomere attrition causes the chromosome ends to register as DNA damage, but until now, it was unknown why telomere homeostasis (a state of biological balance) is lost as we age, resulting in a shift from healthy to unhealthy telomeres. We discuss telomere biology further in our Hallmarks of Aging: Telomere Attrition article.

The new discovery

Back in 1999, researchers Titia de Lange and Jack Griffith discovered that telomeres form loop structures which were thought to be a mechanism for protection [1]. While telomere shortening causes chromosomes ends to resemble broken DNA, it has remained a mystery why telomeres change from healthy to unhealthy with age, that is until now.

Researchers, led by Dr. Tony Cesare, Head of the Genome Integrity Unit at Children’s Medical Research Institute (CMRI) at Westmead, discovered that the telomere loop hides the chromosome end and keeps it protected; however, as the researchers showed, as the telomeres shorten the loop to unravels, exposing the chromosome end and registering as DNA damage [2].

The researchers show that rather than just telomere length, it is their structure that is important. As telomeres shorten with age, it becomes increasingly difficult for them to form the loop structure and thus protect the chromosome. They also discovered that telomeres can also change their structure in response to certain chemotherapy drugs, helping them to kill cancer cells.

Dr. Cesare originally suggested that telomeres played this role back in 2002, but the technology was not easily available at the time to confirm this. Thanks to recent advances in microscopy, it is now possible to see these loops using powerful super-resolution microscopes. The new technology allowed the research team to see 10 times the detail than was available before, allowing them to finally confirm what they had believed was going on.

The research team will now follow up to see how human health correlates with telomere health, which could also shed more light on the complex role that telomeres play in aging.

Conclusion

Telomeres are dynamic structures that are far more complex than originally assumed. It is now known that they play a variety of roles, including epigenetic regulation, and that they act as a protective mechanism for chromosome ends, a cancer failsafe, a replicative clock, and more.

The overly simplistic idea that only telomere length is relevant to aging is clearly incorrect, and as our understanding of telomere biology grows, so do the implications of therapies aimed at improving telomere health.

Literature

[1] Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., & De Lange, T. (1999). Mammalian telomeres end in a large duplex loop. Cell97(4), 503-514.

[2] Van Ly, D., Low, R. R. J., Frölich, S., Bartolec, T. K., Kafer, G. R., Pickett, H. A., … & Cesare, A. J. (2018). Telomere-loop dynamics in chromosome end protection. bioRxiv, 279877.

About the author

Steve Hill

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
  1. July 23, 2018

    Nice summary. I feel like we’re getting closer to major treatment breakthroughs with respect to telomere therapy (and many other breakthroughs also, it seems).

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