Elizabeth H. Blackburn

Adventures at the Ends of Chromosomes


Abstract

What keeps chromosome ends from eroding away and degrading as we age? Telomeres, the protective tips that ‘cap’ and stabilize the ends of chromosomes are important for this. In mammals, each telomere consist of several kilobases of TTAGGG-sequence DNA repeats, bound by proteins (“shelterins”) that make a sheath protecting the telomeric DNA. The integrity of telomeres plays essential roles in human health.

We discovered a special evolutionarily conserved enzyme in cells, telomerase, that adds telomeric DNA to telomeres, replenishing them to counteract the progressive shortening that otherwise often occurs. Telomerase is critical for long-term eukaryotic cell genomic stability, yet curiously, in humans telomere maintenance seems to be limiting throughout our lifespan, and the loss of telomeric protective function plays roles in disease processes.

Telomere shortening in normal cells in humans has been associated with aging-associated diseases – including pulmonary fibrosis, cardiovascular disease, some cancers, diabetes, immune dysfunction and pro-inflammatory states – and higher risks of mortality 1. Telomere shortening potentially plays causal roles in at least some of these disease processes: individuals born with a mutation causing them to have insufficient telomerase enzyme or telomere-maintenance proteins have shorter-than-normal telomeres and suffer premature aging syndromes, including increased incidences of cancers.

Our collaborative studies have shown that telomere maintenance is affected by various events and conditions of life 2. Accelerated telomere shortening in humans is related to – or perhaps caused by – factors including chronic psychological stress, traumatic and chronic stressful life events, some of which in turn are associated with higher risks of aging-related diseases. Physical activity appears to alleviate the impact of stress on leukocyte telomere shortening. Thus, intervention studies are underway to identify how much some of the malign influences on telomere maintenance may be counteracted by preventive actions.


Reading:
1. Blackburn E. Telomeres and Tetrahymena: an interview with Elizabeth Blackburn. Dis Model Mech. 2009 Nov-Dec;2(11-12):534-7. doi: 10.1242/dmm.003418. Epub 2009 Oct 19. No abstract available. PMID: 19841239
2. Blackburn EH, Epel ES. Telomeres and adversity: Too toxic to ignore. Nature. 2012 Oct 11;490(7419):169-71. doi: 10.1038/490169a. No abstract available. PMID: 23060172 


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