1. Introduction

Based on current technology the transit from Earth to Mars would take from 6 to 9 months, dependent on the relative position of the planets at launch. During this time the crew would be exposed to microgravity, the relative absence of gravity on orbit and while traversing deep space far from planetary bodies. Over the past few decades the Soviet/Russian and US space programs have garnered experience on the effects of microgravity exposure aboard Mir and the International Space Station (ISS) over periods comparable to an Earth-Mars transit; the mean duration of the first 23 ISS expeditions was 163 days (SD 42), and 5 cosmonauts have spent periods longer than 9 months aboard Mir. During this period of weightlessness astronauts undergo physiological adaptation to their new environment; the anti-gravity muscles and bones of the lower body begin to atrophy in the absence of gravitational loading forces; venous fluid shifts towards the upper body and head triggering a decrease in total blood volume; and central nervous system (CNS) plasticity results in sensorimotor programs attuned to the novel microgravity environment (Table 1). These changes present little problem to the crew during flight. However, upon return to a gravitational environment (be it Earth or Mars) the cumulative effects of physiological adaptation to microgravity are significant and potentially damaging to crew health and post-landing operations. Here we review the physiological effects of microgravity, the current countermeasures employed, and discuss the health risks and operational consequences upon arrival on the Martian surface.

2. Physiological Effects of Microgravity

Musculoskeletal Human bipedal posture and locomotion is reliant upon the 'anti-gravity' bones and muscles of the lower body. In the microgravity environment the static gravitational load on bones, as well as skeletal impact loads from walking or running, are essentially absent. Astronauts locomote by floating about the spacecraft using only their upper limbs to hold or push off surfaces, with minimal utilization of the lower extremities. On Earth, bone tissue is constantly being remodeled in response to loading forces, primarily by the action of bone-forming osteoblasts and bone resorbing osteoclasts (Cavanagh et al. 2005). In the absence of mechanical loading the balance between bone formation and resorption tilts towards the latter, resulting in demineralization and a net loss of bone. This process begins early, with elevated (60-70%) levels of urinary and fecal calcium, and increased bone resorption markers in urine, observed in the first few days of flight (Buckey 2006). Results from extended missions aboard Mir (LeBlanc et al. 2000) and the ISS (Lang et al. 2004; Buckey 2006) demonstrated a loss of bone mineral density of 1-2% per month (10 times the rate for post-menopausal women (Sirola et al. 2003)) in load-bearing bones such as the lumbar spine (L1-L4), trochanter, pelvis, femoral neck, tibia and calcaneus (Fig. 1A); a net loss of up to 12% for a 180-day ISS mission (Shackelford 2008). Without countermeasures, bone mineral density in astronauts returning from a round-trip mission to Mars would be more than 2.5 standard deviations below the young adult population mean (Williams et al. 2009), the clinical definition of osteoporosis (WHO 1994). The recovery process upon return to Earth can be considerably longer than the time spent in microgravity (Williams et al. 2009), with 50% recovery of bone mineral density at all sites occurring 9 months after long-duration flight (Sibonga et al. 2007), and in some crewmembers never returning to pre-flight levels (Clement 2003).

The postural or 'anti-gravity' skeletal muscles, which maintain upright stance and power locomotion on Earth, atrophy in microgravity (Fig. 1B) with a loss of volume in intrinsic lumbar (-10%), quadriceps (-6%), hamstring (-8%) and calf muscles (-6 to -20%) (LeBlanc et al. 1995; Zange et al. 1997; Fitts et al. 2000). A recent study of ISS crewmembers returning from 6-month missions between 2002 and 2005 found that, despite a systematic exercise regime (running treadmill, cycle ergometer and resistive exercise device), calf muscle volume and power decreased by 13% and 32%, respectively (Trappe et al. 2009). There was also a transition from slow twitch type I (postural) to faster type II (suited to short bursts of activity) muscle fibers in the gastrocnemius and soleus, which, along with the reduction in muscle mass and performance, was indicative of degeneration due to unloading of the muscles of the lower body in microgravity (Trappe et al. 2009). Upon return to Earth's gravitational field, crewmembers report muscle soreness, hamstring and calf tightness, and in some cases symptoms of plantar fasciitis, with recovery of muscle mass and power taking 1-2 months (Clement 2003; Shackelford 2008; Williams et al. 2009).

Cardiovascular Oxygenated blood from the lungs is pumped by the heart through branching arteries to all parts of the body, returning via the venous system to the heart, then on to the lungs to begin the circuit anew. Blood flow delivers oxygen and nutrients and removes waste for excretion. On Earth, upright stance in a gravitational field creates a hydrostatic gradient, with a mean arterial pressure of 70mmHg at the head, 100mmHg at the heart and 200mmHg at the feet. When standing, blood pools in the compliant veins of the lower legs due to gravity, and venous return is facilitated by contraction of skeletal leg muscles when walking and one-way valves preventing back flow. Plasma volume is regulated to within 1% of total volume (Blomqvist and Stone 1983). Upon entering microgravity there is an immediate loss of the hydrostatic gradient, resulting in a shift of venous fluid toward the head of 1-2 liters (Thornton et al. 1977). Although fluid volume is normal by pre-flight standards, volume sensors of the baroreflex sense the cephalad shift as an excess of fluid (Barratt and Pool 2008), resulting in a 17% reduction in plasma volume within 24 h of launch and a gradual loss of red blood cell mass; the net effect is a 10% drop in total blood volume (Williams et al. 2009). Although this fluid redistribution is appropriate for the microgravity environment, the loss of plasma volume would constitute profound hypovolemia on Earth (Barratt and Pool 2008) and is thought to be a primary factor in post-flight orthostatic intolerance (the inability to maintain blood flow to the brain when upright) (Buckey et al. 1996). Upon standing on return to Earth, astronauts may experience tachycardia, falling arterial pressure, and in some cases pre-syncope (dizziness) or syncope (fainting) (Buckey et al. 1996; Fritsch Yelle et al. 1996). The incidence varies with the method of inducing orthostatic stress and the definition of orthostatic intolerance, with estimates ranging from 25% (Fritsch Yelle et al. 1996) to 64% (Buckey et al. 1996) following shuttle landings; normal fluid distribution is restored within 48 h (Williams et al. 2009). Deconditioning of vestibulo-sympathetic reflexes in microgravity (described in the following section) may also contribute to post-flight orthostatic intolerance (Yates and Kerman 1998; Moore et al. 2005b).

Sensorimotor The peripheral vestibular apparatus of the inner ear consists of semicircular canals to sense angular head velocity, and otolith organs that transduce linear acceleration (including gravity). Afferent information from the canals and otoliths is used by the CNS to control upright posture and movement, generate an internal perception of body position and motion, and augment orthostatic tolerance by providing input on body orientation with regard to gravity to the autonomic nervous system. Upon entering microgravity the otoliths no longer sense the constant gravitational acceleration of Earth, and there is considerable evidence that otolith-mediated responses are adversely affected; decreased post-flight gain and up/down asymmetry in eye velocity compensatory for head roll or pitch --in which otolith input encoding head tilt with regard to gravity is integrated with angular input from the canals-- (Clement 1998; Clarke et al. 2000); asymmetrical ocular counter-rolling (a reflex response to lateral head tilts that tends to align the retina with the gravitational vertical) to leftward and rightward tilts both during in-flight centrifugation (Moore et al. 2001) and after flight (Young and Sinha 1998; Moore et al. 2001); deconditioning of otolith-spinal reflexes during simulated ‘falls’ (using elastic cords) in-flight (Reschke et al. 1986; Watt et al. 1986); post-landing postural instability (indicative of deconditioned otolith-spinal reflexes) (Homick and Reschke 1977; Paloski et al. 1999); disruption of head stabilization in response to vertical translation of the trunk (the linear vestibulo-collic reflex (Moore et al. 1999)) during post-flight locomotion with concomitant oscillopsia (Bloomberg et al. 1997); and a correlation between decrements in shuttle landing performance (touchdown speed, vertical velocity and height over runway threshold) and the severity of post-flight postural instability in shuttle commanders (McCluskey et al. 2001). Inflight changes in otolith symmetry, sensitivity, and central integration with canal input may render astronauts prone to spatial disorientation (failure to correctly perceive the position, attitude, or motion of a vehicle) in the hyper-gravity environment of landing; 80% of shuttle crewmembers surveyed (Harm et al. 1999) reported that active head movements provoked illusory sensations of self- and surround-motion during reentry. The otoliths have recently been shown to participate in mediating a vestibulo-sympathetic reflex that maintains orthostatic tolerance when upright. The baroreflex buffers short-term changes in blood pressure with a latency (1.3 s) that depends on the response to pooling of fluid in the legs. The otolithsympathetic reflex has a shorter latency (0.6 s) providing earlier feed-forward excitation to maintain orthostasis (Kaufmann et al. 2002), and deconditioning of this reflex has been proposed as a contributor to post-flight orthostatic intolerance (Yates and Kerman 1998; Moore et al. 2005b).

Sensorimotor performance may also be degraded by microgravity-induced changes in oculomotor, fine motor and cognitive function. In-flight studies have shown an increased number of catch-up saccades during vertical smooth pursuit (Andre-Deshays et al. 1993; Reschke et al. 1999; Moore et al. 2005a), and astronauts exhibited reduced dynamic visual acuity post-flight (Bloomberg and Mulavara 2003; Peters and Bloomberg 2005). Movement dynamics of in-flight joystick control suggested changes consistent with an underestimation of the mass of the hand in microgravity (Ross et al. 1987), such as decreased limb stiffness (Heuer et al. 2003), reduced peak velocity and acceleration in early stages of motion, maintenance of final accuracy by prolongation of the deceleration phase (Sangals et al. 1999; Heuer et al. 2003), and a post-flight reduction in tracking gain (Heuer et al. 2003). There is some evidence from in-flight analysis of horizontal and vertical writing and drawing of Necker cubes (Clement 2003), and from manipulation of the dimensions of a computer generated cube during the zero-g phase of parabolic flight (Clement et al. 2008), that perception of the height of objects and distance of objects in the depth plane are underestimated in weightlessness.

3. Countermeasures

Flight Analogs Although not technically a countermeasure, flight analogs are critical in the development and validation of countermeasures to in-flight deconditioning. The 'gold standard' for replicating the physiological effects of spaceflight on Earth is head down bed rest, where the subject lays on a bed tilted head-down (typically 6º from the horizontal) for periods of weeks to months. Bed rest has been used extensively to simulate aspects of the physiological deconditioning associated with spaceflight (Pavy-Le Traon et al. 2007), reducing mechanical loading along the long-body axis, eliminating the need for coordinated contractions of the anti-gravity muscles, and causing cephalad fluid shifts and relative hypovolemia. Bed rest is effective at simulating (at least qualitatively) the deconditioning effects of spaceflight on bone, muscle, and cardiovascular system function; however, results from a recent 21-day study suggested that microgravityinduced decrements in sensorimotor function were not replicated by head-down bed rest (Moore et al. 2010b). NASA is currently looking for means to adapt head-down bed rest to simulate partial (lunar, Martian) gravity.

Analogs of the sensorimotor effects of spaceflight have recently been proposed. Subjects exposed to sustained (up to 90 min) 3-Gx centrifugation (3-g centripetal acceleration directed along the naso-occipital axis) exhibited sensorimotor symptoms post-rotation similar to those observed in returning astronauts (Ockels et al. 1990; De Graaf and De Roo 1996). However, the effects were short-lived (<60 min) and often accompanied by motion sickness; 40% of veteran astronauts tested experienced nausea and vomiting following 1-hr of 3-Gx centrifugation (Nooij et al. 2004). An alternative approach utilizes electrical stimulation of the vestibular nerve via mastoidal surface electrodes (Galvanic vestibular stimulation - GVS). The Galvanic waveform, a low-frequency (< 1 Hz) sum-of-sines with a maximum amplitude of 5mA, was devised such that sensorimotor performance of normal subjects exposed to acute GVS replicated post-landing data from shuttle and ISS astronauts, namely increased postural sway (MacDougall et al. 2006), impaired locomotion and dynamic visual acuity (Moore et al. 2006), and decrements in piloting performance during high-fidelity simulated shuttle landings (Moore et al. 2010a). Subjective validation was provided by seven veteran astronauts (5 shuttle, 1 ISS, 1 Skylab), who reported that the motor effects and illusory sensations of movement generated by the GVS analog were remarkably similar to their post-landing experience (NSBRI 2006).

Parabolic flight is the only analog capable of providing true weightlessness on Earth. Modified aircraft ascend at a 45° angle before reducing thrust and following a ballistic (parabolic) trajectory; dependent on the length of the arc a range of gravity levels can be generated, including microgravity (0-g; 23 s duration), the moon (0.16-g; 40 s) and Mars (0.38-g; 30 s). Multiple parabolas are flown on a flight (31 for ESA's A300 Zero-g aircraft), but the short duration of each parabola limits its effectiveness as an analog. Neutral buoyancy is used for Extra Vehicular Activity (EVA) training and spacesuit evaluation at the Neutral Buoyancy Laboratory at NASA Johnson Space Center and the NEEMO underwater research habitat off the Florida coast. Partial gravity suspension simulators have been used since Apollo (Johnson and Trader 1970) to prepare astronauts for lunar EVA and spacesuit evaluation. A portion of the subject's weight is borne by a system of cables and springs typically connected to the ceiling, reducing loading on the lower limbs to levels consistent with the moon or Mars. A novel partial gravity simulator for mice has recently been developed that allows normal locomotor activity during extended partial weight bearing (Wagner et al. 2010).

Exercise Exercise has been a staple of long duration space flight since Salyut 1 (1971). Passive treadmills, utilizing elasticized straps to provide loading to the lower body as the crewmember 'ran' in socks on a Teflon® sheet, were present on all Salyut space stations and the final Skylab (4) mission. Two active treadmills with load-inducing 'bungee' straps were on Mir, and two active treadmills with vibration isolation are currently installed on the ISS. Cycle ergometers, which can be pedaled with either the hands or feet, have been standard equipment on US and Soviet/Russian space stations since Skylab 1 and Salyut 4. Resistive exercise devices of varying complexity have been utilized on Skylab, Mir and the ISS; the latest incarnation is the Advanced Resistance Exercise Device (ARED), with piston-driven vacuum cylinders to provide variable resistance, recently delivered to the ISS.

The primary goal of in-flight exercise is to maintain bone, muscle and cardiovascular health. At a 2005 lecture at the Institute for Biomedical Problems in Moscow, a Roscosmos (Russian Federal Space Agency) official boasted that their in-flight exercise protocol had completely reversed the adverse physiological effects of microgravity; the only remaining problem was crew compliance with the demanding exercise regimen. ISS crewmembers currently have a mandatory 2.5 h per day allotted to exercise --which includes set-up and break-down time (Cavanagh et al. 2005), and given the precious nature of crew resources it is difficult to envision more of the day being devoted to training. Moreover, it is clear that current zero-g exercise regimes, even if faithfully followed, are not effective in maintaining bone mineral density (LeBlanc et al. 2000; Lang et al. 2004) or muscle mass and strength (Trappe et al. 2009). More research is required on strategies to better replicate 1-g loading and impact forces during in-flight exercise, and determining optimal exercise equipment and protocols for improved maintenance of bone and muscle during extended periods of micro- and partial gravity exposure.

Pharmacological/Dietary Supplements Calcium, and vitamin D and K supplements, have weak antiresorptive properties; calcium is needed for bone mineralization, vitamin D is involved in regulating calcium deposition (Cavanagh et al. 2005), and vitamin K slows osteoclastic processes via calcium bonding (Kanai et al. 1997). These supplements have been added to the diets of ISS crewmembers in an attempt to lessen in-flight bone loss (Buckey 2006). More potent antiresorptives, and anabolic (bone forming) drugs, are currently under consideration as potential countermeasures to bone loss in microgravity. Bisphosphonates, a powerful class of osteoclast inhibitors, have been shown to maintain bone mineral density in the lumbar spine, femoral neck, trochanter, and pelvis (but not calcaneus) (LeBlanc et al. 2002), as well as minimizing kidney stone formation (Watanabe et al. 2004), during 6° head-down bed-rest studies. However, there is some concern (Cavanagh et al. 2005) that the skeletal bone formed during bisphosphonate administration may not have the mechanical integrity of normal bone (Mashiba et al. 2001b). Intermittent injections of the anabolic parathyroid hormone (PTH) stimulates osteoblasts to increase bone formation (Mashiba et al. 2001a; Cavanagh et al. 2005).

US astronauts routinely consume up to eight 1-gram salt tablets with 900 ml of fluid 2 h prior to reentry in an effort to restore blood volume (Convertino 2005), despite the fact that saline loading has proven ineffective in the prevention of orthostatic intolerance following both headdown bed rest (Vernikos and Convertino 1994) and shuttle flights (Buckey et al. 1996).

Fludrocortisone acts to enhance sodium and fluid retention, but despite early success in restoration of plasma volume following a 7-day bed rest study with fludrocortisone administration (Vernikos and Convertino 1994), was found not to have any positive effect on post-flight orthostatic hypotension in shuttle astronauts (Shi et al. 2004), and its use has been discontinued. Midodrine, a vasopressor/antihypotensive agent that stimulates both arterial and venous constriction, has been shown to maintain orthostatic tolerance after both head-down bed rest (Ramsdell et al. 2001) and shuttle missions (Platts et al. 2006), and is currently under consideration as a countermeasure for ISS crewmembers. Antiemetic medications (promethazine, scopolamine), often combined with a stimulant (dextroamphetamine), are often taken during the acute phase of space motion sickness (Barratt and Pool 2008). Dietary amino acid supplementation has been considered in an effort to maintain in-flight muscle mass and strength (Williams et al. 2009).

Anti-Deconditioning Devices (non-exercise) The Soviet/Russian space program has maintained an almost continuous presence aboard space stations since 1971, and has developed a number of novel devices for crew protection during extended stays in microgravity (RKK Energiya 2000). The most well-known is the light blue Pingvin-3 ('penguin') jumpsuit worn by cosmonauts throughout the workday (Fig. 2A). The garments are embedded with sewn-in elastic straps that impart passive stress on the antigravity muscles, aiding venous return, and providing partial compensation for the lack of gravity by opposing movement. Chibas (Fig. 2B) is a mechanical device that generates lower body negative pressure (60mmHg below ambient pressure), replicating the pooling of fluid in the lower limbs when standing on Earth, and is used to assess cardiovascular fitness prior to reentry. The Braslet ('bracelet') is a set of cuffs and straps that compress the upper third of the thighs in an effort to minimize fluid shift to the upper body during the acute phase of microgravity adaptation.

Electro-stimulation of muscles of the calf, thigh, abdomen, and back, delivered by the Tonus-3 impulse generator, is used as a countermeasure to muscle deconditioning. With the exception of astronauts visiting the Mir space station, these countermeasures have not been widely adopted by the US space program.

Results from recent NASA-funded research have suggested a less intrusive countermeasure approach to bone loss than rigorous exercise. Standing on a high-frequency (90 Hz) low magnitude vibrating plate for 10-20 min per day promoted normal bone formation in hind-limb suspended rats (Rubin et al. 2001), and application of a 30 Hz vibration of 0.3-0.5 g peak magnitude to the soles of the feet for 10 min/day in humans undergoing 90 days of 6° head-down bed rest reduced lumbar intervertebral disc swelling by 41% and reduced the incidence of lower back pain by 46% (Holguin et al. 2009).

Artificial Gravity Artificial gravity (AG) is a potential multi-system countermeasure to bone, muscle and cardiovascular deconditioning. Two basic approaches have been proposed: a large radius, low angular velocity rotation of the spacecraft (von Braun 1952), and small radius, high angular velocity intermittent rotation on a centrifuge. Both techniques generate linear (centripetal) acceleration in the radial direction to replicate the gravitational load experienced on Earth. Large radius AG has the advantage of a low angular velocity requirement to generate 1-g (2 rpm at a radius of 224 m) that minimizes potentially disorienting Coriolis effects, but requires substantial economic resources to develop a large rotating spacecraft. There is little indication that NASA is seriously considering this option. There has been only one application of AG in manned spaceflight; a short-arm centrifuge was flown aboard the Neurolab (STS-90) shuttle mission capable of generating sustained (up to 20 min) 1-g acceleration of human subjects (Fig. 3). Results from four payload crewmembers exposed to in-flight AG suggested a beneficial effect on preservation of otolith-mediated reflexes (Moore et al. 2001; Moore et al. 2005b). A recent 21- day head-down bed rest study exposed treatment subjects to one hour of daily AG (30 rpm; 2.5 g at the feet, 1.0 g at the heart). No discernable effect was seen in preservation of bone (likely due to the limited duration of bed rest) (Smith et al. 2009), but intermittent AG had a positive effect on preservation of muscle mass and strength (Caiozzo et al. 2009; Symons et al. 2009). Post-bed rest testing of vestibular function demonstrated a small negative effect of AG on spatial orientation (Moore et al. 2010b). The fact that NASA cancelled the second (international) phase of this study suggests that AG is currently not a high agency priority.

4. Operational Consequences of Extended Microgravity Exposure

The physiological changes occurring during spaceflight are likely appropriate for microgravity, but crewmembers face obvious risks to their personal health upon return to a gravitational environment that could critically impact mission effectiveness. Under the current countermeasure regime, an astronaut may leave Earth with above-average health but arrive on Mars with osteoporotic 'anti-gravity' bones (Williams et al. 2009) and postural muscles in the lower body weakened to a level equivalent to that of an 80-year-old (Trappe et al. 2009). Ambulatory activities, such as emergency egress and post-landing EVA, place crewmembers at risk for bone fractures and muscle injury. A fracture of the proximal femur (hip), common in low-energy falls in osteoporotic patients, would render an astronaut immobilized and unable to carry out operations; dependent on the level of onboard surgical facilities probably for the rest of the mission. As bone recovery takes longer than the period of microgravity exposure (Sibonga et al. 2007) the risk of fracture will likely remain throughout the planetary stay for an exploration class mission. Moreover, the calcium excreted in-flight from bone resorption increases the risk of kidney stone formation, which have occurred following shuttle flights (Buckey 2006; Shackelford 2008). Muscle weakness will limit the intensity and duration of post-landing activities until strength is restored; a process that takes 1-2 months of rigorous exercise on Earth (Shackelford 2008). The risk of falls would also be elevated in the first 48 h post-landing due to orthostatic hypotension when upright. There is little evidence that cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks (Convertino 2005).

The operational consequences of sensorimotor adaptation are more difficult to define. Space motion sickness generally occurs following gravity transitions (such as orbital insertion and reentry) and is transient (1-2 days) (Williams et al. 2009). Although severe motion sickness may render a crewmember temporarily incapacitated, experienced astronauts tend to be relatively immune; presumably an exploratory Mars crew would be composed of spaceflight veterans. Post-flight deficits in locomotor and postural performance may exacerbate fall risk. Of broader interest is how in-flight sensorimotor adaptation affects a crewmembers ability to operate complex machinery, such as a Mars lander or rover, in a gravitational environment? Surprisingly little has been done to quantify this risk (we have recently received funding from NASA to conduct pre- and post-flight assessment of operator proficiency in ISS crewmembers). Current NASA mission rules dictate that ISS crewmembers cannot operate a vehicle (car or aircraft) for up to 12 days post-landing. The basis for this policy is not publicly available, but likely represents experience gained from post-flight incidents of spatial disorientation. Our analysis of shuttle landing data suggests that even short-duration flights adversely affect piloting performance. A review of the first 100 missions found that 20% of shuttle landings were outside of acceptable limits in terms of touchdown speed (Moore et al. 2008), the majority of which were 'hot' (above target and potentially damaging to the landing gear); in stark contrast to near-perfect performance in pre-flight simulations. The maximum allowable touchdown speed of 217 kts (based on the main gear tire rating of 225 kts (NASA 2000; Jenkins 2001)) was equaled or exceeded on six occasions (Moore et al. 2008). Deficits in post-flight shuttle landing performance have been linked to spatial disorientation induced by head movement and hypergravity (Clark 2002; Moore et al. 2008). The most striking example of operator error during long-duration spaceflight was the collision of the unmanned Progress 234 with the Mir space station in 1997. The commander, after 136 days on orbit, was tasked to remotely pilot the Progress from a distance of 6 km to dock with Mir, using hand controllers and a video display from the point-of-view of the approaching Progress. The collision was attributed to piloting errors in the form of ‘late realization that the closing rate was too high’ (Ellis 2004), likely due to the difficulty in estimating and controlling the relative velocity of Progress from the video display --which required an egocentric mental transformation dependent upon vestibular input (Lenggenhager et al. 2008).

5. Extended Exposure to Partial Gravity

The physiological consequences of long-duration stays in the lower gravitational field of Mars are largely unknown. Is musculoskeletal loading sufficient in 0.38-g to maintain bone and muscle mass at the landing baseline? Will exercise in Martian gravity restore bone and muscle lost during the flight to Mars? How do the cardiovascular and sensorimotor systems adapt to partial gravity? Does the 0.38-g environment mitigate the operational risks described above? Current human partial gravity simulators, such as suspension and parabolic flight, are limited in their ability to conduct extended studies on the effects of Martian gravity. A recent study in mice, using a novel partial weight suspension device that allowed normal locomotor activity over 21- days in a simulated 0.38-g environment, found a 23% decline in mass of the gastrocnemius muscle and a 24% decline in trabecular bone volume at the distal femur compared to full weightbearing controls (Wagner et al. 2010). Arrival on Mars may not end the physiological decline experienced during spaceflight.

6. Conclusions

Microgravity adaptation over periods comparable to an Earth-Mars transit induces significant loss of bone, muscle and total blood volume, and sensorimotor plasticity unsuited to a gravitational environment. Current countermeasures, primarily based on a daily 2.5 h exercise regime, are clearly inadequate to prevent these changes. It is imperative that the remaining decade of ISS utilization focus on improving existing countermeasures and developing novel approaches to maintaining crew health during extended stays in microgravity. And before a manned journey to Mars can be seriously contemplated we need to obtain a much clearer understanding of the physiology of long-duration exposure to partial gravity.

Acknowledgments: This work was supported by NASA grant NNX09AL14G and a National Space Biomedical Research Institute (NSBRI) grant through NASA NCC 9-58 (Drs. Moore & MacDougall), and a grant from the Garnett Passe and Rodney Williams Memorial Foundation (Dr. MacDougall).