Study of Immunosenescence in Aging by NIH, NASA, and ESA

Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab suggesting that immune-suppression is a major barrier to safe, long-term human space habitation and travel.  After review of three decades of International studies on the immune system, there is no doubt that spaceflight changes T cell activation.  Here we present past studies and now offer definitive evidence that early signal transduction events are inhibited by the microgravity (ug) environment of spaceflight.  Human leukocytes were stimulated with T cell mitogens onboard the International Space Station using a 1g centrifuge as the Earth’s 1g control.  Microarray analysis demonstrated significant (p< .05) differential expression of 54 genes in ug vs 1g conditions.  Fifty percent of the genes most significantly inhibited in ug as compared to 1g showed marked over-representation of NFKB binding sites in their promoter regions. Qtpcr confirmed that upregulation of key genes in the NFKB pathway were inhibited in ug. Inhibition of the NFKB pathway leads to activation dysfunction during spaceflight.  Lack of immune response in microgravity occurs at the cellular level. Morover, we have found that decreased immune function in spaceflight in many ways parallel those of aging.  In our upcoming spaceflight studies of early T cell activation on International Space Station, we will investigate the earliest expression of mRNAs, miRNAs and proteins in both man and mouse require gravity for appropriate T cell activation. These new ISS experiments will determine if gravity regulates T-cell activation by several different mechanisms.