## 1 Microgravity Effects in Different Tissues  
Gravity has played a very important evolutionary role in the development of life on Earth, forcing the organisms to evolve the capacity to translate gravity force into biochemical stimuli, responsible for intracellular and molecular changes, conditioning the architectural organization of cytoplasm and nucleus, and then the adaption of organisms to this constant and pervasive force. For this reason, both the reduction of gravity (or microgravity) experienced, for example, on the short/long-term stay in the ISS (International Space Station) and hypergravity (for instance, hyper acceleration in the space flights) represents singular extreme conditions in which a number of cellular changes have been observed. Prolonged microgravity causes several physiopathological effects on tissues such as skeletal, cardiac, smooth muscle, bone, and the nervous system [1; 2]. In addition to cellular/molecular changes, in the cardiovascular system, a situation called \"fluid shift\" takes place where blood accumulates in the head and in the chest region for the absence or reduction of gravity, while on earth blood tends to stay in the lower segments of the body, especially the legs. In this situation, microgravity causes a highly specific response of cardiovascular system with a decrease in plasma volume and circulating blood. Otherwise, it causes an increase of erythrocytes and hemoglobin mass with a decrease in the arterial diastolic pressure of the blood [3]. A large number of studies have also detailed the negative effects of real and simulated microgravity on the immune system and countermeasures have been suggested [4]. Several experiments conducted in rats demonstrated that spaceflight causes a lymphoid organs hypoplasia and alteration in blastogenesis [5]. More recently, microgravity has been shown to reduce the number, differentiation, and polarization of macrophages by affecting the Rat Sarcoma (RAS)/Extracellular signal-regulated kinase (ERK)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway [6]. Moreover, the dendrite maturation and activation of T-cell is also reduced after prolonged microgravity exposure [7]. On the other hand, microgravity increased the resistance of T-cells to dendritic cell activation [8]. Furthermore, cytokine production, such as interferon \(\alpha\)/\(\beta\), is altered after spaceflight [9], and also the immunoglobulin level shows a little increase in total concentration after long-term spaceflight [10]. These data, taken together, suggest that reduction of stress, increased exercise, adequate diet, etc., should be implemented during prolonged space flights in order to minimize adverse effects on the immune system. Moreover, long-term missions in space accelerate muscle atrophy [11] that involves skeletal/postural muscle. In fact, under microgravity conditions, the skeletal muscle system is characterized by \"deconditioning\" with the loss of mass, force, and power with abnormal reflex patterns [12] that limit the astronaut's ability to work in the weightlessness condition. Physiological changes in muscle are due to a combination of factors like increased degradation of muscle proteins without the substitution of newly expressed proteins normally operating as a maintenance mechanism at normogravity on the earth; this will be worsened by subsequent changes of the neuromuscular control of movement strictly connected with profound alterations in muscle fibre size and organization. This mechanism is suggested by another characteristic finding that affects skeletal and cardiac muscle: the transition in myosin heavy chain (MHC) isoform expression, especially observed in rodents, with a downregulation of slow type I MHC and an increased expression of fast type IIx MHC [13]. It has also been assumed that humans can undergo a similar transition, explaining the clinical changes observed in astronauts after long-term spaceflights. More studies both in human and animal models are needed to clarify this situation [14].