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Download the Current Issue of the “Objective View” Newsletter: March 2018

April 5, 2018 - Featured Speaker: Susan Bailey, Ph.D.

Assessing Telomere Length and Telmerase Activity in Twin and Unrelated Astronauts

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Speaker Bio: Susan M. Bailey, Ph.D., is a Professor of Radiation Cancer Biology in the Department of Environmental & Radiological Health Sciences at Colorado State University in Fort Collins, Colorado. Dr. Bailey is currently Vice President elect of the international Radiation Research Society. She also serves as Director of the University Program of Research and Scholarly Excellence in “Cancer Biology & Comparative Oncology”, and of CSU’s Telomeres & Telomerase Laboratory. Dr. Bailey was recently selected as an “Innovator of the Year 2018” by CSU Ventures for her work on technology development and commercialization with the biotech start-up company KromaTiD, Inc. A native of Los Alamos, NM, she received her Master of Science and Doctorate degrees in Biomedical Sciences from the University of New Mexico School of Medicine. As a radiation cytogeneticist with particular interests in telomeres and DNA repair, her research efforts have provided novel insights into basic mammalian telomere biology, and most recently have demonstrated the value of assessing telomere dynamics as an informative biomarker of life stress (e.g., in a non-Western, central India, context), and of exposures in extreme environments (e.g., one year mission aboard the International Space Station) as one of the investigators in the NASA Twins Study.

Talk Abstract: The ends of human chromosomes are capped by telomeres; tandem arrays of repetitive DNA sequence bound by a plethora of associated proteins that serve to protect chromosomal termini from inappropriate degradation and loss. Telomeres also preserve genomic stability by preventing natural chromosomal ends from being recognized as broken DNA (double-strand breaks; DSBs) and triggering inappropriate DNA damage responses. It is well established that telomere length erodes with cellular division and aging due to the end-replication problem, a predicament that causes them to shorten until reaching a critically short length, at which point a permanent cell cycle arrest known as cellular senescence is entered; oxidative stress has also been shown to contribute to telomere erosion. It is becoming increasingly appreciated that telomere length is also influenced by a host of lifestyle factors including, stress (e.g., nutritional, physical, psychological), infection, inflammation, and environmental exposures (e.g., cigarette smoke, air pollution, UV and ionizing radiations). Healthy lifestyles and diets are positively correlated with telomere length, whereas chronic stress and disease are negatively correlated. Indeed, recent research supports telomere maintenance as a key integrating component for the cumulative effects of genetic, environmental, and lifestyle factors on aging; i.e., the rate at which telomeres shorten over time provides a robust biomarker of biological aging. As such, telomere length dynamics is also linked to age-related degenerative pathologies, ranging from reduced immune function and dementia, to cardiovascular disease (CVD) and cancer.

Interestingly, oxidative stress, radiation exposure, and changes in diet and lifestyle, have also been shown to modulate telomerase activity. Telomerase is the specialized reverse transcriptase capable of de novo addition of telomeric repeats onto the ends of newly synthesized telomeres. However, while telomerase activity is prominent in highly proliferative cells like stem, germ-line and cancer, it is virtually absent in normal somatic cells. Of relevance in this regard are our demonstrations of elevated telomerase activity following ionizing radiation (IR) exposure, which was associated with enrichment of critical stem cell compartments; findings consistent with recent evidence supporting telomere length as a determinant of CVD (shorter telomeres associated with increased risk), and cancer (longer telomeres associated with increased risk). Such late effects relevant to spaceflight are largely unknown and controversial, yet have very real potential for influencing performance during long duration missions. Changes in telomere length and telomerase activity over time are also not well understood, particularly as associated with spaceflight and/or ionizing radiation exposures.

We speculated that telomere length dynamics represent a particularly relevant and informative biomarker of health risk for astronauts, as it reflects the combined exposures and experiences encountered during spaceflight. That is, an astronaut’s individual genetic susceptibilities, environmental exposures to galactic cosmic radiation and microgravity, unique nutritional, physical and psychological stressors, are all integrated and captured as changes in telomere length. We have been assessing telomere length and telomerase activity in twin and unrelated astronauts and age/gender-matched controls: pre-flight (to establish baseline); in-flight (to evaluate short-term/temporary changes); and post-flight (to evaluate long- term/permanent changes). Our on-going work is – for the first time – demonstrating changes in human telomere dynamics associated with space flight, supporting the view of telomeres as integrative biomarkers that encompass environmental exposures and a host of life stressors, and therefore are informative of health and health risk – on and off the planet! Funding from NASA is gratefully acknowledged (
NNX14AB02G, NNX14AH51G).

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