The document summarizes several key effects of microgravity on human physiology based on numerous studies. It finds that microgravity leads to cellular changes like cytoskeleton thinning and increased senescence. It also causes musculoskeletal issues like muscle atrophy and bone loss. Further, microgravity compromises cardiovascular function and could impact male reproduction. The greatest health concerns are muscle atrophy and bone loss. Exercise and fluid loading are effective countermeasures but more research is still needed on microgravity's long term impacts and developing new countermeasures.

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The Effects of Microgravity on Human Physiology: From Cellular to Systemic Functions
By: Faizanahmed Munshi, Byrne Summer Science Program (August 2013)
Professor Haym Benaroya, Rutgers University School of Engineering
1. Abstract:
To form an organized and collective review of several effects of microgravity on human
physiology, a state of the art literary review was constructed after studying and analyzing
numerous studies. The main themes of these studies were on how microgravity changes cell
structure, growth, and aging, as well as cardiovascular, reproductive, and musculoskeletal
structural and functional integrity. This review attempts to prioritize the most significant
consequences of microgravity that compromise astronaut function during space flight. It also
calls for the development of effective countermeasures in the form of physical exercise, drug
therapy, and beyond to resolve these issues.
2. Introduction:
As the 21st
century progresses on, human interest in space exploration continues to grow
along with technical advancements made to facilitate transportation into space. With the waning
of the space shuttle era, new and innovative ways to push the boundaries of the final frontier are
being developed. In addition, the International Space Station (ISS) has been in operation for
nearly fifteen years and has had multitudes of astronauts serve missions on that can last up to
several months. This means that astronauts have been, and will be in space for longer durations
of time, raising questions about the effects of space on the human body. Several organizations
have taken a step towards answering such questions. Among them is the National Space
Biomedical Research Institute (NSBRI), an academically based research institute that is
partnering with NASA to perform biomedical research addressing the issues facing long-duration

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space travelers. The NSBRI provides a research cycle with a plan of action for interested parties
that identifies needs and priorities, prepares individual team strategic plans, recruits proposals,
provides funding, and assesses the outcomes to optimize results and share them with the
community and beyond [1]. Although this has been beneficial for the space physiology
community, the number of studies in this field has been limited by small sample sizes due to: the
few space missions conducted in the past, the small number of astronauts that have been in
space, and the current infeasibility of regular space travel for research. To combat this, scientists
have become more innovative, devising techniques and instruments to simulate microgravity on
Earth that include clinorotation of cells, hind-limb unloading of mice [2] and crustaceans [3],
and long-duration head-down bed rest for humans [4] to supplement the samples sent into low-
earth orbit on various space missions. With data coming in from various studies done to learn
about microgravity’s effects on various human body processes, a need to assess the information
and create a comprehensive review of the current knowledge in the field has arose. This can help
in identifying the most pressing issues astronauts face when embarking on long-duration space
missions, so that future studies targeted towards resolving these issues are sponsored and
effective measures are developed.
Some of the most prominent issues facing astronauts in space travel are the result of
weightlessness, which is also referred to as microgravity or zero g. Astronauts experience many
alterations in the way their bodies are structured and how they work due to the lack of gravity,
which is the only constant mankind has known in the ever-evolving environment that is Earth.
Some of these changes were identified very early in the space era, and others were more recently
discovered. Such alterations include bone loss, muscle atrophy, and cardiovascular
deconditioning. These adverse effects of prolonged weightlessness have been central areas of

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concern for NASA and have led to studies that help in understanding the pathophysiology and
mechanisms behind bone demineralization, muscle atrophy, and orthostatic intolerance in
weightlessness. As time progressed, other aspects of human physiology worthy of consideration
when planning long-duration manned space missions began to be studied in a zero g
environment. These included changes at the cellular level in microgravity, such as alterations in
cellular structure, growth, and aging. Sertoli cell function was also been studied in a zero g
environment to gain insight on humans’ reproductive capabilities and whether they are altered in
space. This literature review organizes findings in these diverse yet still connected studies and
then centers on the most prominent effects of microgravity on humans: muscle atrophy and bone
loss. This state of the art also attempts to prioritize these alterations in physiology due to
weightlessness in order to facilitate future studies that can increase knowledge on the
mechanisms behind these occurrences, as well as to aid in the development of suitable
countermeasures.
3. Effects of Microgravity at the Cellular Level:
3.1 Cytoskeleton
Microgravity has been hypothesized to affect cell structure, growth, proliferation, and
differentiation. The cell’s structural backbone is its cytoskeleton, consisting of protein-based
microtubules and microfilaments that provide structural support and stabilize the cell’s shape [5].
The cytoskeleton is involved in proliferation, motility, migration, protein synthesis, transport,
signal transduction, and apoptosis [6, 7]. A 2001 study reports that the cell cytoskeleton also
plays a role in mechanisms of adaptation to gravitational changes, a role that becomes altered by
long-term microgravity [8]. This suggests that microtubules act as load-bearing compression
elements and actin as tension elements [9]. In the study, human endothelial cells (EC) were

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cultured and exposed to simulated microgravity via clinorotation and showed a significant
decrease in proliferative activity. This decrease supports the notion that cytoskeletal structures,
particularly actin filaments, are affected by the lack of gravity. These changes in the cell
cytoskeleton are described as thinning microfilaments that redistribute to the borders of the cell.
This thinning of actin filaments, in addition to a quantitative down-regulation of actin via a
transcriptional mechanism, has been hypothesized to be an adaptive response to microgravity.
This response helps to avoid redundant actin fibers accumulating in the cell. However, the
molecular mechanisms involved in this process and their relevance to endothelial cells’ response
to gravitational unloading need to be explored further [10].
3.2 Cellular Growth & Senescence
Endothelial cells are key in maintaining functional integrity of the vascular wall and
preventing cardiovascular complications that astronauts have been documented with. Reversible
stimulation of EC cell growth in microgravity has been shown, and exposure to microgravity
activates the same pathways as any other stressful condition, including up-regulation of heat
shock protein 70 and down-regulation of interleukin 1 alpha (IL-1α). IL-1α is an inhibitor of
endothelial cell growth and a promoter of cellular senescence, and its down-regulation is what
seems to be responsible for the stimulation of cell growth in simulated microgravity. Therefore,
although some spaceflight has been suggested to model aging, in the case of endothelial cells
aging is offset by this down-regulation of IL-1α [10]. Conversely, another more recent study
suggests that simulated microgravity induces cellular senescence in neuronal rat PC12 cells by
up-regulating aging associated protein pathways, namely p53 and p16 protein pathways. In
addition, the activity of intracellular antioxidant enzymes were increased after microgravity
onset, suggesting that cellular senescence is induced via oxidant stress. These findings are able

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to explain the macroscopic findings of aging in post flight astronauts such as learning and
memory disturbance, mild hypothyroidism, increased stress hormones, altered mitochondrial
function, and changes in gene expression that direct fibroblast cells to premature senescence
[11]. Non-human studies done regarding aging and microgravity, such as ones done using the
fruit fly Drosophila melanogaster as a model organism, also suggest the notion that microgravity
induces effects similar to aging. Therefore, although one particular EC study suggests stimulated
growth in microgravity, it is more likely that microgravity exposure leads to an overall increase
in cellular senescence that may be detrimental to the astronaut’s lifespan upon return to the
Earth. Therefore, it is important to direct some attention towards understanding the more long-
term implications of weightlessness in outer space in order to develop countermeasures against
cellular senescence.
4. Cardiovascular Issues Related to Spaceflight:
Compromised cardiovascular function has been reported in astronauts during space flight
and is an area of concern for researchers of the NSBRI, who formed a Bioastronautics Critical
Path Roadmap (BCPR) in 2000 that prioritized risks for the cardiovascular system in spaceflight.
Data suggested that orthostatic intolerance and reduced aerobic capacity were the highest priority
for astronauts to address in regards to compromised operational capability and highest
probability of occurrence [12]. In other words, these issues were deemed to be the most pressing
of the cardiovascular concerns faced by astronauts. Orthostatic intolerance is the inability to
remain in an upright posture while maintaining adequate perfusion of the brain; it is related to
orthostatic hypotension, in which blood pressure decreases. It is a serious health problem that can
impair crewmembers’ performance during re-entry into the Earth’s atmosphere and immediately
after landing, with a recovery time ranging between several days to weeks. Possible causes are

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fluid loss, muscle wasting and reduced aerobic fitness. Microgravity alters the hydrostatic
pressure gradient, resulting in a cephalic fluid shift that can lead to multiple hormonal responses,
resulting in increased fluid loss. Orthostatic hypotension could result from this microgravity-
related loss of fluid. This hypothesis is supported by the discovery of volume loading with saline
prior to landing as a successful countermeasure. Exposure to microgravity and its associated
effects on the musculoskeletal system can also alter cardiovascular function due to decreased
aerobic fitness and reduced blood volume. However, astronauts who undergo in-flight exercise
reduce musculoskeletal atrophy but still experience post-flight orthostatic intolerance, suggesting
that muscle atrophy cannot exclusively account for the intolerance.
While the aforementioned causes do not individually account for the severity of
orthostatic intolerance documented in astronauts, it is possible they act simultaneously under
microgravity and result in orthostatic hypotension. However, a more likely hypothesis is plastic
changes in the vestibular system, mainly the otoliths in the ears, after exposure to microgravity.
Evidence has shown that an altered gravitational environment produces significant adaptive
changes in the vestibular system, and the vestibular otoliths organs elicit changes in sympathetic
nervous system activity, which includes blood pressure regulation. While preliminary studies
support this hypothesis, further research is needed to validate these findings, and to develop
countermeasures to address this concern [13].
5. Microgravity’s Effects on Reproduction Physiology, Particularly Sertoli Cell Function:
As interest deepened in the role of microgravity in altering human physiology, questions
began to be posed on human reproductive physiology. In the future, it is possible that humans
will begin to spend significant portions, maybe even the entirety, of their lives away from the
Earth’s 1 g environment. Weightlessness could affect reproductive capabilities of humans, and

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several animal studies have been done concerning spaceflight’s effect on the reproductive
system. Male dogs on a satellite for 22 days showed a 30-70% increase in atypical spermatozoa,
while rats in several space missions experienced decreases in testicular weight and number of
spermatogonia, as well as lower circulating testosterone levels [14]. Data also shows that
astronauts experienced a decrease in testosterone secretion during space flights.
At the cellular level, scientists observed damages to the cytoskeleton of testicular ells in
culture, similar to cytoskeleton changes observed in a plethora of other somatic cells. The same
group conducted a study in 2010 to evaluate the influence of zero g on Sertoli cells, which play a
key role in germ cell development and regulating spermatogenesis. Evidence also shows that an
antioxidant system plays a role in protecting somatic and germ cells from oxidant damage, which
can occur during spaceflight. The Sertoli cell line from a mouse testis was analyzed for
cytoskeletal and sex hormone binding globulin (SHBG/ABP) changes, antioxidant content under
simulated microgravity, and lactate concentration. SHBG/ABP (ABP being Androgen Binding
Protein) are proteins essential for germ cell survival and development, and serve as good markers
for Sertoli cell function. Lactate is a preferred energy substrate for germ cells, and is produced by
Sertoli cells.
Results showed cytoskeleton damage similar to the previously tested testicular cell line,
with a disorganized and fragmented microtubular array and altered cell shape. These results are
also similar to the cell cytoskeleton changes seen in human EC cells, as well as in glial cells [15],
thyroid cells, lymphocytes, as well as bone osteoblasts, which will be discussed later. This
suggests that microgravity affects the integrity of specialized cells across the body, and calls to
action a need to develop countermeasures that can prevent or stop these changes by the time
astronauts begin more long duration space missions.

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The study stated that the expression of SHBG/ABP was also affected, with no
immunoreactive signal detected through testing in cells maintained at zero g. This may
significantly impair spermatogenesis when combined with the fact that lactate concentration
slightly but significantly decreased in zero g compared to control values. Microgravity also
increased the level of oxidative stress in Sertoli cells, a finding that suggests cellular senescence.
Microgravity also seems to disturb the antioxidant defense system in Sertoli cells, and these
effects combined could result in male infertility, a consequence that should be seriously
considered and explored in the future before long-duration or even permanent manned space
missions are designated [14]. In addition, future studies need to be conducted to study the all-
important female reproductive system in a zero g environment, to assess if the human race can be
continued successfully in the event that humans begin spending entire lifetimes in outer space.
6. Microgravity’s Effect on Muscle Atrophy & Bone Loss
6.1 Muscle Atrophy
The most paramount health concerns for astronauts embarking on space missions are the
effects of microgravity on muscles and bones. In low gravity environments, weight-bearing
muscles become less active and decrease in performance. Astronauts documented complaints of
a delayed onset of muscle soreness [16], resulting in a plethora of studies done on muscle
changes pre- and post- spaceflight. Studies show that skeletal postural muscles experience mass
loss compared to non-weight bearing muscles. Without gravity, muscles noticeably decrease in
fiber size, protein synthesis rates drop by approximately 15% in a long-term spaceflight [17], and
actin thin filaments degrade. The greatest level of atrophy was found in the soleus, or calf muscle
[18], which is a slow-twitch Type I muscle. After about 270 days in space, the muscle mass
attains a constant value of about 70% its original mass [19]. In contrast, fast-twitch muscles

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were less affected by microgravity. After 14 days of spaceflight, a study showed that paraspinal
muscles of rats remarkably decreased the slow Type I myosin heavy chain (MHC), muscle fiber
number, and muscle volume. Scientists concluded that microgravity induced slow-twitch muscle
atrophy in the paraspinal muscle, while conversely the fast Type II MHC increased after the 14
days of spaceflight, indicating a phenotypic change of slow to fast muscle fibers. In humans
however, studies show that there is a common atrophy in both slow and fast muscle fibers.
Overall, these atrophies manifest macroscopically to loss of muscle mass, force and power,
increased muscle fatigue, and abnormal reflex patterns, all of which are collectively termed
“deconditioning”.
The study done on paraspinal muscles in rats determined that Type I muscle atrophy is
caused by microgravity-induced decrease of the myocyte enhancer factor 2C (MEF2C) protein
expression. In this study, scientists noted that the expression of 42 genes changed in the
microgravitational environment. Most importantly, there were increases in the expression of heat
shock protein 70 and t complex polypeptide 1, and decreases in MEF2C and its related genes’
expressions. MEF2C expression increased after 9 days ground recovery, suggesting that it plays
a key transcriptional role in skeletal muscle atrophy and regeneration under microgravity [19].
Regulating this expression genetically or pharmacologically could be used in therapy for type I
muscle atrophy in not only astronauts, but also bedridden patients who exhibit similar symptoms
due to disuse of weight-bearing muscles.
This atrophy is of special concern not only while in space, but also upon reentry to a 1 g
environment, as the musculoskeletal system must bear the force of gravity after days, weeks, or
even months in space. To address these concerns, countermeasures have already been put into
effect in most current space missions. They include in-flight exercise, which has shown to reduce

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calf muscle loss from 13% to 7% if astronauts use a treadmill for 200 min per week [20]. One
study documented that astronauts exercised 2 hours per day inflight, using a treadmill and cycle
ergometer that simulates gravity and prevents muscle atrophy, bone demineralization, and
cardiovascular deconditioning [19]. Apart from exercise machines, hormonal or steroidal
measures to combat muscle atrophy must also be developed and studied for effectiveness and
safety. As space-missions increase in duration, muscle atrophy can worsen over time, especially
if exercising 2 hours every 24 hours might not be possible. Attaining more convenient
countermeasures, such as pharmacological measures, must be the next step in resolving this key
issue.
6.2 Bone Loss
In addition to muscle atrophy, significant bone loss also occurs when exposed to
microgravity, as documented from astronaut logs from space missions, in vitro studies during
spaceflights, as well as ground-based bed rest and in vitro studies. In the skeletal system, two
main cell types are responsible for bone remodeling: osteoblasts, which are bone forming cells,
and osteoclasts, which are bone resorbing cells. Osteoblast in vitro studies show changes in cell
shape, suggesting cytoskeleton reorganization might be involved [21]. In rats, there was noted
metaphyseal bone loss, as well as an increase in bone resorption. There was also a noted decrease
in periosteal growth, and demineralization that was not affected by an intake of dietary calcium.
One possible underlying mechanism for this bone demineralization is altered systemic hormone
or local growth factor levels [22]. A particular study of interest used the human osteosarcoma
cell line MG-63 to examine whether microgravity alters the gene expression of collagen Iα1 and
alkaline phosphatase, which characterize osteoblast differentiation, and osteocalcin, which
characterizes mineralization. Results showed a significant reduction in the collagen Iα1, alkaline

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phosphatase, and osteocalcin gene expression in microgravity, suggesting that microgravity
alters osteoblast differentiation and that isolated osteoblasts are sensitive to microgravity [22].
Overall, this may explain the characteristic decrease in bone formation and increase in
resorption, which leads to bone loss.
Studies in rats show the bone loss values stabilize after the second week in space and
bone cellular activities reached equilibrium, while bone formation recovery started on the tenth
day of suspension in microgravity [21]. These findings in rats are consistent with Frost’s
hypothesis that bone can adapt through an initial period of more rapid change in bone mass,
followed by stabilization at a new level. Even with all of these findings, questions still remain on
how gravity directly affects osteoblast and osteoclast mechanisms, and how recovery after
microgravity exposure compares to normal bone growth and remodeling.
Scientists know that reduced mechanical use because of hypodynamia (decrease forces)
and hypokinesia (decrease movements) leads to bone loss in space, similar to disuse-osteoporosis
in Earth [23]. Data from several missions, including MIR and Skylab, show that bone loss is site-
specific and that there is no complete recovery after return to the Earth. Thus, there is a need not
only to investigate different bones in the body’s reaction to microgravity, but also in different
areas of the same bones. Even with excessive training preflight and during flight, prolonged
exposure to microgravity results in 1-2% bone mass loss per month [24]. Targeted treatment or
prevention strategies would be useful not only for astronauts in space, but also osteoporosis-
affected patients on Earth [23]. Furthermore, even when the bone reformation recommences, it
does not seem to follow a normal remodeling mechanism as it would in a 1 g environment, as
astronauts still show significant bone loss, loss of strength, and increased risk of fracture
compared to preflight values.

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One 2011 study attempted to uncover the mechanism of bone loss in weightlessness by
examining the effects of microgravity on both the bone-producing osteoblasts and bone-
resorbing osteoclasts. They sent up murine osteoblasts and osteoclasts in culture on a Foton M3
satellite and analyzed them. They found an increase in the total number of discrete resorption pits
in microgravity-exposed osteoclasts in contrast to ground-control values. Exposure of osteoblasts
to microgravity altered cell microtubule organization by increasing the presence of thicker,
bundled, and looped microtubules that were shorter and wavier than ground controls. Focal
adhesions, structural components of osteoblasts that connect the extracellular matrix to
intracellular actin microfilaments, are involved in the transduction of mechanical forces into
downstream molecular signaling [9]. With exposure to microgravity, they decreased in size and
number. The decrease in size is of particular importance because the size of focal adhesions
correlates with the amount of force acting on them [25]. With the decreased gravity in outer
space, the molecular signaling in osteoblasts could be disrupted, leading to impairment of their
bone-forming function. Other structural changes noted in the study were extended osteoblast cell
shapes, as well as more disrupted, fragmented, or condensed nuclei. The change in nuclei could
have serious genetic implications that need to be explored in further studies.
An interesting observation in the study that has long been suggested by previous reports
is the increase in osteoclast activity in microgravity. This, coupled with the compromised
osteoblast structural integrity and lack of proper function can attribute to the pronounced bone
loss that not only astronauts experience in microgravity, but also elderly patients undergo as they
age and experience osteoporosis [26]. This is also supported by the notion that exposure to
microgravity leads to cellular senescence, effectively accelerating aging [11]. In fact, the changes
in bone seen in astronauts correlate with those observed in bedridden patients, modeling

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osteoporosis [27]. The bed-rest study also documents changes in bone microarchitecture that can
explain the increased risk of fracture and weakness attributed to post flight astronaut bone
strength.
In 2013, the concern for risk of bone loss in astronauts due to long duration missions in
microgravity led NASA to convene a Bone Summit panel to review medical data and evidence
from astronauts to come up with countermeasures for minimizing the detrimental effects on bone
health. Data was reviewed from 35 astronauts who served on spaceflight missions between 120-
180 days and divided by who had utilized an advanced resistive exercise device (ARED), who
had been scanned by quantitative computed tomography (QCT) at the hip, had hip bone strength
estimated by finite element modeling, or had lost >10% areal bone mineral density (aBMD) at
the hip or lumbar as measured by Dual X-Ray Absorptiometry. These were reviewed to
determine the efficiency of each test in most accurately determining bone loss and recovery in
astronauts.
There is an aBMD decline of 1.0-1.5% per month in astronauts in space [28] while only
0.5-1.0% per year in the elderly on Earth, which shows the significant bone loss experienced by
astronauts. Data shows that using an ARED in addition to a cycle ergometer and treadmill
reduces aBMD decline in astronauts to only 0.3-0.5% per month, implying that this device is an
effective countermeasure to the pronounced loss in aBMD. However, this efficiency may not
show the entire picture. The panel believed that DXA tests, which measure aBMD,
underestimated bone loss and that more effective tests were needed to truly understand the level
of bone loss experienced by astronauts. QCT and FEM testing were deemed much more
insightful because they can provide additional information regarding spaceflight-induced

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changes and recovery after return that DXA cannot. Thus, more countermeasures needed in
addition to exercise to prevent bone loss and improper repair.
The study also included data of changes in bone turnover markers N-telopeptide (NTX),
measured from urine specimens. The data suggest that bone resorption increased early during
long-duration missions and remained elevated throughout exposure to microgravity, but then
were restored to normal levels upon return to Earth. This finding indicating increased resorption
early in the missions is supported by the 2011 study on osteoclast and osteoblast cells in
microgravity, which also claims increased osteoclast activity, resulting in bone resorption, early
in microgravity exposure [29].
In terms of in-flight countermeasures, as mentioned above, the cycle ergometer and
treadmill in addition to an ARED have been effective in combating some bone loss accelerated
by microgravity. Pharmacological measures, including bisphosphonate therapy, are being
considered or are under trial for use to counter spaceflight related bone loss. Overall, the panel
recommends that measures of bone structure are key determinants of bone strength [30] that can
be measured by OCT-based testing. They offer the following recommendations: (1) Inclusion of
QCT of the hip for risk surveillance, (2) use of FEM to investigate the effect of spaceflight on
hip strength, (3) optimize effectiveness by changing risk mitigation approaches such as preflight
selection of astronauts and inflight countermeasures such as drug therapy.
7. Conclusion
Although much progress has been made in better understanding the effects of
microgravity on human physiology, there are numerous areas of interest still untouched by
research teams. Of the areas that have been explored, some more than others the changes
microgravity makes on muscle and bone structure and function are most pronounced and

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paramount to astronaut safety during and after the flight is over. Even long-term effects of
microgravity-induced bone loss and muscle atrophy have yet to be fully studied or understood,
underlining the key theme that there is still much left to investigate about these health effects. In
addition, genetic studies related to microgravity exposure are in their infancy and offer promising
countermeasures to these effects. If humanity is to fully engage in long-duration space missions
or even embark on a permanent colony in outer space, it not only needs to develop the
technology to get there and stay there, but also be sure that the population is capable of
surviving, being healthy, and reproducing in a safe and proper manner. That can only be done
once humans better understand the effects of spaceflight and zero g environments on the human
body and its intricate mechanisms, which have only experienced a 1 g environment until the last
50 years or so. To continue forward, more involvement by governments in sponsoring their
respective R&D organizations needs to be done, along with better outreach programs to
encourage students to enter the field of science, medicine, and engineering in order to meet the
demands that are made by the pushing boundaries of science everyday. The fields of space
biology and human physiology in space should increase their exposure to attract the interests of
experts who will be able to collaborate with other members of various disciplines and
backgrounds, ranging from cell and molecular biology to mechanical and aerospace engineering,
physics, and astronomy. Further studies need to be conducted to build upon the limited ones
done on the even more limited sample of data, in order to gain more insight on the short and long
term effects of microgravity on human physiology, as well as to study and develop
countermeasures that can treat or prevent the detriments associated with spaceflight. Only then
can mankind achieve the goals it has set to conquer and thrive in space.
8. Appendix:

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1. Clinorotation: Reduction of the effects of gravity on an object (i.e. cell culture) using a
clinostat, a device that uses rotation to simulate microgravity.
2. Hind-limb unloading: A method of simulating microgravity on Earth by lifting mice by the
tail with traction tape, leaving only the front legs on the ground [16].
3. Bone demineralization: The loss of minerals, including calcium and phosphorus, from the
bone [31]. This results in a loss in bone density.
4. Muscle Atrophy: Wasting away of the muscles due to degeneration of muscle fibers.
Condition resulting from reduced muscle mass, which is due to disuse, undernourishment, or
aging of the muscles [31].
5. Cardiovascular Deconditioning: A microgravity-induced condition that consists of
decreases of circulating fluid volumes, arterial blood diastolic pressure, and ventricular
stroke volume. The negative effects manifest themselves mostly upon the reentry to Earth.
They consist mainly of dizziness, increased heart rate and heart palpitations, and an inability
to assume the standing position [32].
6. Signal Transduction: A process in which a cell converts and amplifies an extracellular
signal into an intracellular signal that affects some function of the cell [5].
7. Apoptosis: Programmed cell death. A normal part of a cell’s growth and maintenance [5].
8. Heat Shock Protein 70: A stress-induced chaperone protein that binds to microtubules and
protects the centrosome and intermediate filaments during heat shock [18].
9. Oxidant Stress: Comes from the free radical theory of aging, which proposes that reactive
oxygen species (ROS) produced in the mitochondria cause damage to cellular
macromolecules, leading to senescence [11].
10. Vestibular System: The sensory system mainly located in the inner ear that deals with
balance and gravity by detecting the movements of the head.
11. Frost’s Hypothesis: Harold Frost's Mechanostat paradigm of mechanically induced bone
adaptation in a maturing "tension/compression" bone. Important in osteoporosis and
microgravity-related situations, in which less is required of bone, leading bone loss.
12. Advanced Resistive Exercise Device: An exercise device used by astronauts in space
missions since 2009 that can deliver up to 600 pounds of force resistance and provide high
loads to the lower back, hip, knee, and ankle joints [29].

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13. Cycle Ergometer: A stationary bicycle with an ergometer to measure the work done by the
exerciser.
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