Task Assessing Telomere Lengths and Telomerase Activity in Astronauts
Last Published:  07/31/19 10:05:33 AM (Central)
Short Title: Telomere Lengths
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Human Health Countermeasures (HHC) Element
Other:
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:

Hypothesis: Telomeric proteins aren’t just for telomeres anymore. For example, TRF1 and TRF2 have multiple interacting binding partners, including some that are telomere specific, like Protection of Telomeres (POT)1 and tankyrase1, and some involved in DNA repair (e.g., ATM, MRN, PARP2, WRN, BLM). Telomerase is also known to interact with many telomeric, as well as non-telomeric proteins (including DNA repair proteins), and extra-curricular/pro-tumorigenic activities of telomerase independent of its classical role in telomere length maintenance - including enhanced repair - have beenproposed.

SPECIFIC AIMS

Aim 1. Assess telomere lengths and telomerase activity

Aim 1. Assess telomere lengths and telomerase activity pre-flight to establish baseline levels.

Aim 2. Assess telomere lengths and telomerase activity

in-flight to establish short-term (temporary?) changes.

Aim 3. Assess telomere lengths and telomerase activity

post-flight to establish long-term (permanent?) changes.

Aim 4. Investigate potential mechanisms (e.g., oxidative stress) and mitigation strategies (e.g.,antioxidants).
This aim will be accomplished with in vitro experimentation combining various treatment strategies with assessment of telomere lengths and telomerase activity (as appropriate) to investigate underlying mechanisms of shortening and effective strategies of intervention. Approaches will include: 1) induction of oxidative stress (Hydrogen Peroxide treatment) and alleviation of oxidative stress (antioxidant treatment; e.g., Resveratrol, Protandim); 2) evaluation of senescent fractions, which are expected to accompany significant telomere shortening; and 3) evaluation of changes in stem cell compartments, which are expected to accompany changes in telomerase activity.

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