What are the consequences of shortening the telomeres

How the ends of chromosomes affect cell aging

By investigating the processes that take place at the ends of chromosomes, Heidelberg scientists have uncovered an important mechanism that leads to a better understanding of cell aging. The focus is on the length of the chromosome ends, the so-called telomeres, which can be influenced experimentally. The work carried out at the Center for Molecular Biology of the University of Heidelberg (ZMBH) opens up new approaches for the development of therapies for tissue loss and organ failure, which are related to the aging of cells, the senescence. The research recently published in the journal Nature Structural & Molecular Biology could also be of relevance in the treatment of cancer.

Every cell contains a set of chromosomes in which a large part of the genetic information is stored in the form of DNA. This information must be protected so that the cell can function properly. The ends of the chromosomes, the telomeres, play an important role and protect the chromosomal DNA from degradation. “You can imagine telomeres like the plastic caps on shoelaces. Without these caps, the ends will fray, and ultimately the entire shoelace can no longer fulfill its function, ”explains Dr. Brian Luke. His research group at the ZMBH is primarily concerned with the question of how telomeres protect the DNA.

It is known in science that telomeres become shorter with each cell division and are ultimately so short that they can no longer protect the chromosomes. The unprotected chromosome ends send out signals that ensure that the cell no longer divides. This condition is known as "senescence". With advancing age, there are more and more senescent cells that can promote tissue loss and organ failure. "With certain diseases, patients have short telomeres from birth and are therefore often exposed to severe tissue loss and functional disorders of organs at an early stage," explains the Heidelberg scientist.

The research group around Dr. Luke has now found that switching transcription on or off at the telomeres can have a significant effect on their length. Transcription is the process by which information in DNA is rewritten into RNA molecules. It was only recently demonstrated in telomeres, but the functional significance of this discovery has remained unclear. Molecular biologists Bettina Balk and André Maicher have now been able to show that RNA itself plays a key role in regulating telomere length - especially when it binds to telomere DNA and forms a so-called "RNA-DNA hybrid molecule" .

“We have experimentally influenced the number of RNA-DNA hybrids at the chromosome ends. We can increase or decrease the speed of cellular senescence directly by changing the length of the telomere, ”explains Bettina Balk. According to André Maicher, this could be the first step towards telomere-based treatment methods for tissue loss or organ failure. In the case of diseases, it remains to be checked whether changing the transcription rates of telomeres can actually improve the state of health. This approach is also important for cancer cells that do not age and are virtually immortal. "The regulation of the length of telomeres by influencing the transcription could therefore also be used in cancer therapy," emphasizes Dr. Hatch.

The junior research group of Dr. Luke is a member of the Aging Research Network (NAR) at Heidelberg University and is financially supported by the Baden-Württemberg Foundation. Further funding is provided by the German Research Foundation as part of the Collaborative Research Center “Cellular Quality Control and Damage Limitation” (SFB 1036) of the Ruperto Carola.

Original publication:
B. Balk, A. Maicher, M. Dees, J. Klermund, S. Luke-Glaser, K. Bender & B. Luke: Telomeric RNA-DNA hybrids affect telomere length dynamics and senescence; Nat. Struct. Mol. Biol. (8 September 2013), DOI: 10.1038 / nsmb.2662