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Project Title:  Telomeres and the One Year Mission Project Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/31/2019  
End Date: 01/30/2026  
Task Last Updated: 11/29/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bailey, Susan M. Ph.D. / Colorado State University 
Address:  Environmental and Radiological Health Sciences 
1618 Campus Delivery 
Fort Collins , CO 80523-1618 
Email: susan.bailey@colostate.edu 
Phone: 970-491-2944  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jeevarajan, Antony  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC19K0434 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Solicitation / Funding Source: 2017-2018 HERO 80JSC017N0001-BPBA Topics in Biological, Physiological, and Behavioral Adaptations to Spaceflight. Appendix C 
Grant/Contract No.: 80NSSC19K0434 
Project Type: FLIGHT 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
Task Description: The ultimate goal of the studies proposed here is to establish temporal profiles of human telomere length dynamics and DNA damage responses of importance for maintenance of human health and performance during long-duration deep space missions. We hypothesize that telomere length dynamics (changes over time) represent a particularly relevant and informative biomarker of health for the astronauts, as it reflects the combined experiences and exposures encountered during spaceflight. That is, an astronaut's individual genetic susceptibilities, unique lifestyle stresses encountered (e.g., nutritional, psychological, physical), and particular environmental exposures (e.g., altered atmospheres, microgravity, space radiations) are all integrated and captured as changes in telomere length. Thus, the rate at which telomeres shorten provides a general measure of health that can be linked to aging, as well as to risk of developing age-related pathologies, ranging from reduced immune function and dementia, to cardiovascular disease and cancer. Importantly, functional telomeres are also essential for maintaining genomic integrity and stability, as they protect chromosomal termini from inappropriate degradation, and prevent these natural DNA ends from being recognized as broken DNA and triggering inappropriate DNA damage responses (DDRs). To identify trends in adaptations to human health and performance during long-duration low-Earth orbit, we propose telomere length and DDR/cytogenetic measures pioneered and validated in the NASA Twins Study/first One Year Mission, across the Integrated One-Year Mission Project onboard the International Space Station and the concurrent ground analog (prolonged isolation) component.

Research Impact/Earth Benefits: Identifying interactive effects of genetic and nongenetic telomere length determinants and DDRs will improve understanding of aging and aging trajectories (disease risk), as well as guide future studies and development of potential strategies for improving health-span, not only in astronauts on long-duration missions, but for those on Earth, too.

Task Progress & Bibliography Information FY2022 
Task Progress: To date, and taken together, our results suggest that chronic low-dose, low-dose rate exposure to the space radiation environment contributes to the changes in telomere length dynamics and DDRs observed. Chronic oxidative stress correlated with telomere length dynamics and damaged telomeres, and heterogeneous telomere lengths, were consistent with transient activation of ALT (telomerase independent telomere length maintenance mechanism). Cytogenetic analyses revealed direct evidence of IR (irradiation)-induced DNA damage (chromosome abnormalities) during spaceflight (inversions, satellite associations), some of which persisted after spaceflight (inversions). Reduced white blood cell counts correlated with radiation dose, reflective of lymphocyte radiosensitivity (cell killing), and suggestive of redistribution of leukocyte subsets as previously reported. Thus, changing cell population dynamics in response to chronic space radiation exposure may be at least partially responsible for our observations. Telomeres 2 will further explore and validate these foundational results, as well as provide critical mechanistic insight necessary for better understanding potential adverse health and/or aging impacts of long-duration spaceflight.

Bibliography Type: Description: (Last Updated: 12/15/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Cornforth MN, Bedford JS, Bailey SM. "Destabilizing effects of ionizing radiation on chromosomes: Sizing up the damage." Cytogenet Genome Res. 2021 Sep;161(6-7):328-51. Review. https://doi.org/10.1159/000516523 ; PMID: 34488218 , Sep-2021
Articles in Peer-reviewed Journals Bailey SM, Luxton JJ, McKenna MJ, Taylor LE, George KA, Jhavar SC, Swanson GP. "Ad Astra – telomeres in space!" Int J Radiat Biol. Published online: 26 Jul 2021. https://doi.org/10.1080/09553002.2021.1956010 ; PMID: 34270368 , Jul-2021
Articles in Peer-reviewed Journals Grigorev K, Foox J, Bezdan D, Butler D, Luxton JJ, Reed J, McKenna MJ, Taylor L, George KA, Meydan C, Bailey SM, Mason CE. "Haplotype diversity and sequence heterogeneity of human telomeres." Genome Res. 2021 Jul;31(7):1269-79. https://doi.org/10.1101/gr.274639.120 ; PMID: 34162698; PMCID: PMC8256856 . , Jul-2021
Articles in Peer-reviewed Journals Luxton JJ, Bailey SM. "Twins, telomeres, and aging-in space!" Plast Reconstr Surg. 2021 Jan 1;147(1S-2S):7S-14S. https://doi.org/10.1097/PRS.0000000000007616 ; PMID: 33347069 , Jan-2021
Articles in Peer-reviewed Journals Cunningham K, Hinton TG, Luxton JJ, Bordman A, Okuda K, Taylor LE, Hayes J, Gerke HC, Chinn SM, Anderson D, Laudenslager ML, Takase T, Nemoto Y, Ishiniwa H, Beasley JC, Bailey SM. "Evaluation of DNA damage and stress in wildlife chronically exposed to low-dose, low-dose rate radiation from the Fukushima Dai-ichi Nuclear Power Plant accident." Environ Int. 2021 Oct;155:106675. Epub 2021 Jun 10. https://doi.org/10.1016/j.envint.2021.106675 ; PMID: 34120002 , Oct-2021
Articles in Peer-reviewed Journals Nelson CB, Alturki TM, Luxton JJ, Taylor LE, Maranon DG, Muraki K, Murnane JP, Bailey SM. "Telomeric double strand breaks in G1 human cells facilitate formation of 5' C-rich overhangs and recruitment of TERRA." Front Genet. 2021 Mar 25;12:644803. https://doi.org/10.3389/fgene.2021.644803 ; PMID: 33841503; PMCID: PMC8027502 , Mar-2021
Project Title:  Telomeres and the One Year Mission Project Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/31/2019  
End Date: 01/30/2026  
Task Last Updated: 11/30/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bailey, Susan M. Ph.D. / Colorado State University 
Address:  Environmental and Radiological Health Sciences 
1618 Campus Delivery 
Fort Collins , CO 80523-1618 
Email: susan.bailey@colostate.edu 
Phone: 970-491-2944  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jeevarajan, Antony  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC19K0434 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Solicitation / Funding Source: 2017-2018 HERO 80JSC017N0001-BPBA Topics in Biological, Physiological, and Behavioral Adaptations to Spaceflight. Appendix C 
Grant/Contract No.: 80NSSC19K0434 
Project Type: FLIGHT 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
Task Description: The ultimate goal of the studies proposed here is to establish temporal profiles of human telomere length dynamics and DNA damage responses of importance for maintenance of human health and performance during long-duration deep space missions. We hypothesize that telomere length dynamics (changes over time) represent a particularly relevant and informative biomarker of health for the astronauts, as it reflects the combined experiences and exposures encountered during spaceflight. That is, an astronaut's individual genetic susceptibilities, unique lifestyle stresses encountered (e.g., nutritional, psychological, physical), and particular environmental exposures (e.g., altered atmospheres, microgravity, space radiations) are all integrated and captured as changes in telomere length. Thus, the rate at which telomeres shorten provides a general measure of health that can be linked to aging, as well as to risk of developing age-related pathologies, ranging from reduced immune function and dementia, to cardiovascular disease and cancer. Importantly, functional telomeres are also essential for maintaining genomic integrity and stability, as they protect chromosomal termini from inappropriate degradation, and prevent these natural DNA ends from being recognized as broken DNA and triggering inappropriate DNA damage responses (DDRs). To identify trends in adaptations to human health and performance during long-duration low-Earth orbit, we propose telomere length and DDR/cytogenetic measures pioneered and validated in the NASA Twins Study/first One Year Mission, across the Integrated One-Year Mission Project onboard the International Space Station and the concurrent ground analog (prolonged isolation) component.

Research Impact/Earth Benefits: Identifying interactive effects of genetic and nongenetic telomere length determinants and DDRs will improve understanding of aging and aging trajectories (disease risk), as well as guide future studies and development of potential strategies for improving health-span not only in astronauts on long-duration missions, but for those on Earth, too.

Task Progress & Bibliography Information FY2021 
Task Progress: Complement of Integrated Protocols for Human Exploration Research (CIPHER) Selected for Flight (Oct 2020). First mission launch ~December 2021; first BDC ~April/May 2021. Working on details of sample collection before, during, and after spaceflight.

Together with cell-by-cell analyses, approaches for more high throughput analyses (e.g., ddPCR) are being tested and optimized.

We are developing machine learning strategies for predicting telomere length outcomes, which will become more and more reliable/informative as the models see more data. We are also seeking ways to test mechanisms; e.g., to assess the influence of chronic oxidative stress on telomere length. We evaluated telomere length in blood samples from humans climbing Mt. Everest, and matched twin non-climbing controls.

Established Telomeres 2 stem/progenitor cell evaluation as part of Standard Measures; collaborating with Brian Crucian.

Established NASA and home institution (Colorado State University-CSU) Institutional Review Boards (IRBs) – continuing process. Awaiting crew selection and recruitment into the Telomeres 2 study.

Bibliography Type: Description: (Last Updated: 12/15/2021) 

Show Cumulative Bibliography Listing
 
Articles in Other Journals or Periodicals Grigoriev K, Foox J, Bexdan D, Butler D, Luxton JJ, Reed J, McKenna MJ, Taylor L, George KA, Meydan C, Bailey SM, Mason CE. "Haplotype Diversity and Sequence Heterogeneity of Human Telomeres." Genome Research, in press as of December 2020. bioRxiv preprint server. https://doi.org/10.1101/2020.01.31.929307 , Dec-2020
Articles in Peer-reviewed Journals Afshinnekoo E, Scott RT, MacKay MJ, Pariset E, Cekanaviciute E, Barker R, Gilroy S, Hassane D, Smith SM, Zwart SR, Nelman-Gonzalez M, Crucian BE, Ponomarev SA, Orlov OI, Shiba D, Muratani M, Yamamoto M, Richards SE, Vaishampayan PA, Meydan C, Foox J, Myrrhe J, Istasse E, Singh N, Venkateswaran K, Keune JA, Ray HE, Basner M, Miller J, Vitaterna MH, Taylor DM, Wallace D, Rubins K, Bailey SM, Grabham P, Costes SV, Mason CE, Beheshti A. "Fundamental biological features of spaceflight: Advancing the field to enable deep-space exploration." Cell. 2020 Nov 25;183(5):1162-84. Review. https://doi.org/10.1016/j.cell.2020.10.050 ; PMID: 33242416 , Nov-2020
Articles in Peer-reviewed Journals Luxton JJ, McKenna MJ, Taylor LE, George KA, Zwart SR, Crucian BE, Drel VR, Garrett-Bakelman FE, Mackay MJ, Butler D, Foox J, Grigorev K, Bezdan D, Meydan C, Smith SM, Sharma K, Mason CE, Bailey SM. "Temporal telomere and DNA damage responses in the space radiation environment." Cell Rep. 2020 Dec 8;33(10):108435. https://doi.org/10.1016/j.celrep.2020.108435 ; PMID: 33242411 , Dec-2020
Articles in Peer-reviewed Journals Luxton JJ, McKenna MJ, Lewis A, Taylor LE, George KA, Dixit SM, Moniz M, Benegas W, Mackay MJ, Mozsary C, Butler D, Bezdan D, Meydan C, Crucian BE, Zwart SR, Smith SM, Mason CE, Bailey SM. "Telomere length dynamics and DNA damage responses associated with long-duration spaceflight." Cell Rep. 2020 Dec 8;33(10):108457. https://doi.org/10.1016/j.celrep.2020.108457 ; PMID: 33242406 , Dec-2020
Articles in Peer-reviewed Journals Trinchant NM, MacKay MJ, Chin C, Afshinnekoo E, Foox J, Meydan C, Butler D, Mozsary C, Vernice NA, Darby C, Schatz MC, Bailey SM, Melnick AM, Guzman M, Bolton K, Braunstein LZ, Garrett-Bakelman F, Levine RL, Hassane D, Mason CE. "Clonal hematopoiesis before, during, and after human spaceflight." Cell Rep. 2020 Dec 8;33(10):108458. https://doi.org/10.1016/j.celrep.2020.108458 ; PMID: 33242405 , Dec-2020
Articles in Peer-reviewed Journals Bezdan D, Grigorev K, Meydan C, Pelissier Vatter FA, Cioffi M, Rao V, MacKay M, Nakahira K, Burnham P, Afshinnekoo E, Westover C, Butler D, Moszary C, Donahoe T, Foox J, Mishra T, Lucotti S, Rana BK, Melnick AM, Zhang H, Matei I, Kelsen D, Yu K, Lyden DC, Taylor L, Bailey SM, Snyder MP, Garrett-Bakelman FE, Ossowski S, De Vlaminck I, Mason CE. "Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers." iScience. 2020 Dec 18;23(12):101844. Available online 25 November 2020. https://doi.org/10.1016/j.isci.2020.101844 ; PMID: 33376973; PMCID: PMC7756145 , Dec-2020
Project Title:  Telomeres and the One Year Mission Project Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 01/31/2019  
End Date: 01/30/2026  
Task Last Updated: 03/29/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bailey, Susan M. Ph.D. / Colorado State University 
Address:  Environmental and Radiological Health Sciences 
1618 Campus Delivery 
Fort Collins , CO 80523-1618 
Email: susan.bailey@colostate.edu 
Phone: 970-491-2944  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Jeevarajan, Antony  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC19K0434 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation / Funding Source: 2017-2018 HERO 80JSC017N0001-BPBA Topics in Biological, Physiological, and Behavioral Adaptations to Spaceflight. Appendix C 
Grant/Contract No.: 80NSSC19K0434 
Project Type: FLIGHT 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes (IRP Rev M)
Human Research Program Gaps: (1) CVD-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease (IRP Rev L)
Task Description: The ultimate goal of the studies proposed here is to establish temporal profiles of human telomere length dynamics and DNA damage responses of importance for maintenance of human health and performance during long-duration deep space missions. We hypothesize that telomere length dynamics (changes over time) represent a particularly relevant and informative biomarker of health for the astronauts, as it reflects the combined experiences and exposures encountered during spaceflight. That is, an astronaut's individual genetic susceptibilities, unique lifestyle stresses encountered (e.g., nutritional, psychological, physical), and particular environmental exposures (e.g., microgravity, galactic cosmic rays) are all integrated and captured as changes in telomere length. Thus, the rate at which telomeres shorten provides a general measure of health that can be linked to aging, as well as to risk of developing degenerative age-related pathologies, ranging from reduced immune function and dementia, to cardiovascular disease and cancer. Importantly, functional telomeres are also essential for maintaining genomic integrity and stability, as they protect chromosomal termini from inappropriate degradation, and prevent these natural DNA ends from being recognized as broken DNA and triggering inappropriate DNA damage responses (DDRs). To identify trends in adaptations to human health and performance during long-duration low-Earth orbit, we propose telomere length and DDR/cytogenetic measures pioneered and validated in the NASA Twins Study/first One Year Mission, across the Integrated One-Year Mission Project onboard the International Space Station and the concurrent ground analog (prolonged isolation) component.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2019 
Task Progress: New project for FY2019.

Bibliography Type: Description: (Last Updated: 12/15/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2019