Lack of gravity or reduction of the influence of gravity (unloading with ineffective activity, reduced cardiovascular need for work, and lack of postural change signals) more than likely affects all physiological systems, with broad consequences.
What was seen in space, Head Down Bed Rest (HDBR), and as we age has also been seen (or should be expected to be seen) from sitting as well. These changes are generally characterized by the rapid onset of an overall metabolic disorder characterized by loss of blood volume and red cell mass, fluid and electrolyte shifts, and a reduction in endothelium lining affecting the integrity of blood vessels, bone, and other systems that depend on the nitric oxide (NO) generated by shear forces, which are seriously reduced in Gravity Deprivation Syndrome (GDS).
Central among these metabolic changes are insulin resistance, hyperlipidemia, decreased fat oxidation, a shift in substrate use toward glucose, reduced protein synthesis, loss of collagen, muscle atrophy with a shift in muscle-fiber type from slow to fast, ectopic fat storage with fatty infiltration of the liver and bone marrow with a consequent form of anemia, and reduced anabolic neuroendocrine secretions such as growth hormone, testosterone, and leptin. Rapid bone loss with possible ectopic calcium deposits round off the metabolic picture. Reduced sensitivity of sensory systems and reflexes, with decreased sensitivity of central and peripheral balance and coordination systems, is a prime feature of reduced gravity consequences as well. In addition, viral reactivation, immune deficiency with resistance to antibiotics, inflammation, and a reduction in telomere length and telomerase activity have all been observed.