During the NASA Twin Study Previous, telomere length changes were observed in blood cells. Telomeres are specific sequences at the end of the chromosomes, protecting them from deterioration, much like the plastic tip at the end of a shoelace. Muscle atrophy is one of the main characteristics of astronauts in space. The only way to minimize muscle atrophy is through intensive exercise every day. However, the effects of telomere length changes in adult muscle cells remain unexplored. Interestingly, our lab recently developed a new method which allowed, for the first time, telomere length measurements in specialized cells within the adult muscles, including human tissues. We found that telomere shortening is a district feature of muscle stem cells (MuSCs) in atrophied muscles as well as in stem cells after repeated cycles of muscle damage and repair, similar to the ones observed in intensive exercise.
Aim 1: Determine the combined effects of weightlessness and radiation exposure on telomere length of MuSCs.
Aim 2: Define the cellular outcomes MuSC-depended telomere length changes during muscle atrophy.
Aim 3: Investigate the molecular mechanism of telomere length in MuSCs.
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We will utilize the mouse hindlimb suspension model of disuse atrophy combined with gamma irradiation to evaluate their effect on telomere length, using a new method developed in our lab. Next, we will monitor for the first time in vivo the number of MuSCs using two-photon microscopy using genetically modified mice we recently generated and will further investigate the extent of apoptosis and senescence during atrophy. These studies are expected to provide a comprehensive analysis of the exact cellular dysfunction of shortened telomeres. Last, we will query the levels of a specific telomeric binding protein and its effect on persistent DNA damage at the telomeric sites. These experiments are expected to elucidate the molecular crosstalk leading to shortened telomeres in muscle cells
This experiment is currently in progress. Results will be available at the conclusion of the study.