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Simulated Microgravity Recapitulates Aspects of Biological Aging in Humans.

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Simulated microgravity exposure mirrors key aspects of human aging, altering immune cell gene expression and metabolism. This research provides a model for studying aging and developing countermeasures for spaceflight and Earth-based conditions.

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Area of Science:

  • Human physiology
  • Space biology
  • Immunology
  • Aging research

Background:

  • Spaceflight and microgravity significantly impact human physiology, potentially mimicking aspects of biological aging.
  • The precise molecular mechanisms linking microgravity to aging phenotypes are not fully understood.

Purpose of the Study:

  • To investigate immune cell alterations associated with natural aging and simulated microgravity using whole-genome transcriptomic profiling.
  • To compare transcriptional changes in peripheral blood mononuclear cells (PBMCs) from individuals before and after spaceflight exposure, as well as across a 9-year longitudinal study.

Main Methods:

  • Whole-genome transcriptomic profiling of PBMCs.
  • Comparison of samples from the Stanford 1,000 immunomes Project, including longitudinal samples and samples exposed to simulated microgravity via rotating wall vessel bioreactors.
  • Single-Cell Energetic Metabolism by Profiling Translation Inhibition (SCENITH) for metabolic profiling.

Main Results:

  • Microgravity-induced transcriptional changes closely paralleled individual aging trajectories, affecting metabolic, musculoskeletal, and circulatory systems.
  • Observed changes included alterations in nutrient sensing, chronic inflammation, proteostasis, cellular senescence, and metabolic regulation.
  • SCENITH profiling confirmed metabolic adaptations, showing reduced mitochondrial dependence and minimal compensatory glucose dependence in immune cells, mirroring aging biology.
  • Approximately one-third of participants exhibited unique aging trajectories, partly predictable by simulated microgravity exposure.

Conclusions:

  • Simulated microgravity serves as a scalable platform for modeling human biological aging.
  • This approach can accelerate the identification of countermeasures for both spaceflight and age-related diseases on Earth.
  • Understanding immune cell responses to microgravity provides insights into fundamental aging processes.