Microgravity-induced skeletal muscle atrophy in women and men: implications for long-duration spaceflights to the Moon and Mars

Abstract

The inclusion of women on spaceflights has historically been limited. Recently, the first woman who will travel to the Moon was selected, and more women are participating in long-duration spaceflights. However, physiological data from real and simulated microgravity exposure are limited in women. This investigation studied women (n = 8, 34 ± 1 yr) and men (n = 9, 32 ± 1 yr) who underwent 2 (women) or 3 (men) mo of simulated microgravity (6° head-down tilt bed rest). Quadriceps and triceps surae muscle volumes were assessed via MRI before bed rest, bed rest day 29 (BR29, women and men), bed rest day 57 (BR57, women), and bed rest day 89 (BR89, men). Volume of both muscle groups decreased (P < 0.05) in women and men at all bed rest timepoints. Quadriceps muscle volume loss in women was greater than men at 1 mo (BR29: −17% vs. −10%, P < 0.05) and this 1-mo loss for women was similar to men at 3 mo (BR89: −18%, P > 0.05). In addition, the loss in women at 2 mo (BR57: −21%) exceeded men at 3 mo (P < 0.05). For the triceps surae, there was a trend for greater muscle volume loss in women compared with men at 1 mo (BR29: −18% vs. −16%, P = 0.08), and loss in women at 2 mo was similar to men at 3 mo (BR57: −29%, BR89: −29%, P > 0.05). The collective evidence suggests that women experience greater lower limb muscle atrophy than men at least through the first 4 mo of microgravity exposure. More sex-specific microgravity studies are needed to help protect the health of women traveling on long-duration orbital and interplanetary spaceflights.

NEW & NOTEWORTHY This study adds to the limited evidence regarding sex-specific responses to real or simulated microgravity exposure, which collectively suggests a sex-specific muscle atrophy profile, with women losing more than men at least through the first 4 mo of weightlessness. Considering the increase in women being selected for space missions, including the first women to travel to the Moon, more physiological data on women in response to microgravity are needed.

INTRODUCTION

As the National Aeronautics and Space Administration (NASA) looks to return to the Moon with a more diverse astronaut crew, including the recent selection of the first woman who will leave Earth’s orbit and travel to the Moon (1, 2), understanding the sex-specific responses to microgravity exposure is more relevant than ever. This will become more important as the mission durations increase, especially when travel to Mars becomes a reality. Women have constituted only ∼2 of every 10 crewmembers on missions aboard the Mir and International Space Stations, and none of the crewmembers aboard the original Skylab orbital station or on the original expeditions to the Moon were women. Our estimates from the scientific literature dating back to the 1960s (3, 4) suggest that women represent <10% of the subject population of Earth-based microgravity simulation studies. As a result, there are limited medical and physiological data on women and few direct comparisons between women and men in response to real or simulated microgravity exposure. This includes human health components (e.g., cardiovascular, skeletal, immunologic, sensory, reproductive, behavioral, circadian) beyond the skeletal muscle focus of the current investigation (5–9).

We had the unique opportunity to participate in two microgravity simulation studies, one focused only on men and the other focused exclusively on women. Both were conducted at the same bed rest facility using similar methodologies. We were selected to complete the skeletal muscle mass measurements and were able to use the same protocols for both studies. This allowed us to make some of the few well-controlled comparisons between men and women of microgravity-induced skeletal muscle atrophy. Findings from the separate studies have been published previously (10, 11) and the sex-specific comparisons are reported here.

MATERIALS AND METHODS

Subjects

Subjects for these studies were recruited from France and other parts of the European Union (Table 1) and were judged healthy and enrolled following a medical and psychological screening exam. All of the procedures, risks, and benefits associated with the experimental testing were explained to the subjects before they signed a consent form adhering to the guidelines of the Human Use Committees of all the participating institutions.

Table 1.

Characteristics of the bed rest subjects

Group	n	Age, yr	Height, cm	Weight, kg
Women	8	34 ± 1	163 ± 2	55.6 ± 1.4
Men	9	32 ± 1	173 ± 1	70.8 ± 2.0

General Bed Rest Procedures

The data presented here were generated from two bed rest studies, one examining women and one examining men, using the widely accepted analog of 6° head-down tilt (HDT) bed rest to simulated weightlessness (12, 13). Both studies were conducted at the Institute for Space Physiology and Medicine (MEDES) in Toulouse, France (10, 14), and used the same methods and procedures, allowing for a direct comparison between the responses of the women and men. Each study consisted of a baseline data collection period, 60 (women) or 90 (men) days of 6° HDT bed rest, and a recovery period that varied in duration depending on the specific measurement. The baseline data collection period provided time for the subjects to equilibrate to the standardized diet and for prebed rest data collection on each of the subjects. All meals and snacks were prepared for the subjects. During bed rest, the subjects remained in the 6° head-down position or horizontal for all activities including eating, bathing, and excretory functions. Continuous video and medical staff monitoring ensured compliance to the bed rest.

Muscle Volume

Following 1 h of horizontal (0°) supine position rest to control for the influence of postural-related fluid shifts on muscle size (15), magnetic resonance imaging (MRI) was completed on each subject before bed rest, at 1 mo of bed rest, and at the end of bed rest (women: bed rest day 29 (BR29), BR57, men: BR29, BR89) to determine the volume of the m. quadriceps femoris and m. triceps surae (i.e., mm. gastrocnemius and soleus) (Fig. 1). Specific procedures for the MRI have been described by us in detail previously (10, 11, 16, 17). Subjects were in supine position and their heels were fixed on a nonmetallic foot restraint to control joint angle (and thus muscle length), scan angle, and to minimize compression of the legs against each other and against the MRI table. Reproducibility across sessions was controlled by the use of the foot restraint and the use of specific anatomical landmarks viewed on an initial scout scan for each individual. Subjects also refrained from excessive muscular exercise for at least 10 h before any test. Imaging was completed in the Radiology Department of Rangueil Hospital, connected to the bed rest facility, in a 1.5-T scanner (Intera, Philips Medical Systems) during the 60-day bed rest study and a 1.0-T scanner (Somatom Impact, Siemens) during the 90-day bed rest study. Following the scout scan, interleaved transaxial images of 8 mm thickness were taken from the top of the thigh to the ankle. MR images were transferred electronically from the scanner to a personal computer and analyzed using manual planimetry. In our laboratories, coefficients of variation for measurements made on separate days on the same individuals are ∼2%. The coefficients of variation measuring the same image are less than 2%.

Figure 1.

Representative MR images of the thigh (top; FOV: 48 × 48 cm; 512 × 512 pixels) and calf (bottom; 35 × 35 cm; 512 × 512 pixels) muscles before and at day 57 of bed rest for one of the women. Images are to scale for pre- and postbed rest size comparisons, as well as thigh and calf muscle size comparisons. The white circular image near the thigh and calf is a color/density standard placed in the field of view. The m. quadriceps femoris (top) and m. triceps surae (i.e., mm. gastrocnemius and soleus) (bottom) were assessed for muscle volume as we have previously described (10, 11). RF, rectus femoris; VL, vastus lateralis; VI, vastus intermedius; VM, vastus medialis; Sol, soleus; LG, lateral gastrocnemius; MG, medial gastrocnemius.

Statistics

A two-way analysis of variance (gender and time) with repeated measures on the time factor was completed on the change in thigh and calf muscle volume during the bed rest period. When appropriate, comparisons were made with Tukey’s post hoc test. Statistics on absolute and relative changes in muscle volume within the women and men have been reported previously (10, 11). Significance was accepted at P < 0.05. Means are presented ± SE.

RESULTS

Skeletal muscle mass responses of the women and men at 1 mo and after 2 (women) or 3 (men) mo of HDT bed rest are presented in Fig. 2 and Table 2. Both groups lost significant amounts of muscle mass in both muscle groups at each measured timepoint compared with prebed rest (P < 0.05) (10, 11). Quadriceps muscle volume loss in women was greater than men at 1 mo (BR29: −17% vs. −10%, P = 0.0002) and this 1-mo loss for women was similar to men at 3 mo (BR89: −18%, P > 0.05). In addition, the loss in women at 2 mo (BR57: −21%) exceeded men at 3 mo (P = 0.004). For the triceps surae, there was a trend for greater muscle volume loss in women compared with men at 1 mo (BR29: −18% vs. −16%, P = 0.08), and loss in women at 2 mo was similar to men at 3 mo (BR57: −29%, BR89: −29%, P > 0.05).

Figure 2.

Change in m. quadriceps femoris (top) and m. triceps surae (i.e., mm. gastrocnemius and soleus) (bottom) muscle volume in women and men after 1, 2, or 3 mo of simulated microgravity. Measurements were made with magnetic resonance imaging (MRI) as we have previously described (10, 11). *P < 0.05 from prebed rest (10, 11); **P < 0.05 between women and men; †P = 0.08 between women and men.

Table 2.

Muscle volume of the quadriceps and triceps surae in response to bed rest in the women and men

	Quadriceps		Triceps Surae
Women		Δ		Δ
Pre	716 ± 39		374 ± 15
BR29	596 ± 32*	−120 ± 8	307 ± 13*	−67 ± 3
BR57	564 ± 31*	−151 ± 10	266 ± 10*	−107 ± 6
Men
Pre	973 ± 47		494 ± 33
BR29	879 ± 42*	−93 ± 13	415 ± 24*	−79 ± 10
BR89	793 ± 39*	−179 ± 14	350 ± 18*	−144 ± 16

Values are presented in cm³. BR29, bed rest day 29. *P < 0.05 vs. prebed rest. These data have been reported previously in separate publications (10, 11).

DISCUSSION

Crew selection for future long-duration space missions, such as colonization of the Moon or a mission to Mars, will be predicated on humans being able to preserve health and fitness during these exploration missions. The current findings from two spaceflight simulation studies suggest that women are more susceptible to weightlessness-induced muscle atrophy. These data agree with previous evidence from 4 mo (119 days) of simulated microgravity in a limited number of women (n = 3) who lost more muscle mass than men (18). Interestingly, the magnitude of difference that we report between women and men in the quadriceps at 1 mo (∼7%) still persisted at 4 mo (∼8%). However, compared with our findings between women and men in the triceps surae (soleus and gastrocnemius) at 1 mo (∼2%), the difference at 4 mo was even larger (∼11%). These 4-mo findings are also supported by the current findings that show at 2 mo women had already lost the amount of muscle mass men lost in 3 mo. Collectively, the current findings and those of Shackelford et al. (18) suggest that the difference in microgravity-induced muscle atrophy between women and men likely persists beyond 4 mo of microgravity exposure. It is also noteworthy that with respect to the existing literature and bed rest studies using gold standard measures of muscle mass (i.e., MRI), the study by Shackelford et al. (18) and our current data from men represent the two longest bed rest studies, and the current data from women represent the longest bed rest study on a large cohort of women.

The quadriceps and triceps surae muscles were the focus of the current investigation because they are critical for ambulation and extravehicular activities that likely will be required of space crews visiting the Moon or Mars. The current findings should be viewed in the context that a change in muscle size is closely linked to changes in muscle function (19) and the magnitude of muscle atrophy observed in only a few months of bed rest in the current study is similar to that encountered during 50 years of age-related atrophy (i.e., 25–75 yr) (17, 20, 21). Thus, the decline in muscle volume in both women and men during microgravity exposure is critically large (10, 11, 18, 22–24).

During spaceflight, the muscle mass loss of an astronaut compared with preflight levels will dictate her or his own decline in muscle performance and health. This is why we chose to present the findings as a percentage change from prebed rest (i.e., the relative loss; Fig. 2). Interestingly, examination of the data from women and men (Table 2) suggests that during the first month, women lost even more absolute quadriceps muscle mass than men, further highlighting the magnitude of the muscle atrophy. Separate from the typical considerations of physical function, muscle mass also serves as the largest amino acid reservoir for the immune system. Studies have shown that there are negative consequences to confronting a medical event with low muscle mass (25–29), suggesting broader implications for preserving muscle mass on long-duration missions. In addition, it is now established that muscle serves as an endocrine organ, communicating with numerous other organs (i.e., interorgan cross talk) and likely coregulating numerous aspects of human health (30, 31).

Access to space travel is expanding at a record pace, with private and public programs providing women with more opportunities to go to space than ever before. The data presented here and the small amount of existing literature suggest that the muscle atrophy response to microgravity exposure is different between women and men, at least through the first 4 mo and likely beyond. Gaining further insights into this apparent sex-specific skeletal muscle atrophy issue as it relates to long-duration missions (i.e., 6 mo to 1 year or more) is necessary. However, this will likely be difficult to obtain as the magnitude of decline in most physiological systems that would be observed with 6 mo to 1 year or more without any physical exercise might be inappropriately large. In addition, all astronauts are required to complete inflight exercise countermeasures for health and safety, and any comparisons between women and men are influenced by the variable countermeasures completed across the astronauts (24, 32). Therefore, a more appropriate path to understand sex-specific responses to microgravity (including the muscle atrophy issue) and to obtain data to better protect the health of future crewmembers may be through well-controlled long-duration bed rest studies with only exercise countermeasure groups. These studies could examine the responses of women and men to specific exercise programs and consider different combinations of exercise modes and doses. Of course, the current findings should be considered during the design of any future real and simulated microgravity investigations. The skeletal muscle responses of women and men to exercise countermeasures should also be interpreted in the context of the current findings.

DATA AVAILABILITY

Data will be made available by the authors upon reasonable request.

GRANTS

This work was supported by NASA NNJ04HF72G (to S. Trappe and T. Trappe) and the Swedish National Space Board (to P. Tesch).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

T.T., P.T., B.A., and S.T. conceived and designed research; T.T., P.T., B.A., and S.T. performed experiments; T.T., P.T., B.A., and S.T. analyzed data; T.T., P.T., B.A., and S.T. interpreted results of experiments; T.T. prepared figures; T.T. drafted manuscript; T.T., P.T., B.A., and S.T. edited and revised manuscript; T.T., P.T., B.A., and S.T. approved final version of manuscript.