A new study published in Science has found that telomere lengths do not fall under a general range as previously believed. Instead, different chromosomes have separate telomere length distributions, challenging the current understanding of how telomere lengths are regulated. Telomeres play a crucial role in cell division by capping the ends of chromosomes, ensuring complete replication. Telomerase, an enzyme, is responsible for maintaining telomere length during cell division, impacting overall health and disease.
Carol Greider, a professor at UC Santa Cruz, has been studying telomeres and telomerase for over 30 years and was awarded the Nobel Prize in Physiology or Medicine in 2009 for her work in this field. Despite her extensive research, the findings of this latest study surprised her. Short telomeres are known to lead to age-related degenerative diseases, while overly long telomeres can predispose individuals to certain cancers. This discovery highlights the importance of understanding the molecular processes that regulate telomere lengths.
The study, led by Kayarash Karimian, a former Ph.D. student of Greider’s lab, involved measuring telomeres in 147 individuals. The researchers found that the average telomere length across all chromosomes was around 4,300 bases of DNA, but individual chromosomes showed significant variations from this average. This variability in telomere lengths on specific chromosome ends suggests that they may be key factors in triggering stem cell failure, leading to health issues.
To make precise measurements at the molecular level, Greider’s team employed nanopore sequencing, a groundbreaking technique for DNA and RNA sequencing invented at UC Santa Cruz. Nanopore sequencing has been essential for significant genomic advances, including the completion of the gapless human genome and sequencing of COVID-19 genomes. The study proves that this technology continues to advance scientific research, potentially revolutionizing drug development and diagnostics in the future.
The precise DNA reads allowed Greider’s team to identify the regions adjacent to telomeres where telomerase regulates telomere length. Targeting these regions and the proteins that bind there could lead to the development of new drugs for disease prevention. The “telomere profiling” process through nanopore sequencing could serve as a model for creating additional assays for drug screening. The widespread potential of this technique in research, diagnostics, and drug development could uncover new mechanisms for regulating telomere length and inform approaches to cancer and degenerative diseases.
Funded by grants from the National Institutes of Health, the Johns Hopkins Bloomberg Distinguished Professorship, and the National Science Foundation Graduate Research Fellowship Program, this study sheds light on the chromosome-specific nature of telomere lengths and offers insights into potential targets for disease prevention and treatment. The researchers hope that further exploration of telomere regulation will lead to new approaches for addressing cancer and degenerative diseases in the future.
