Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures

Long-duration spaceflights result in a substantial decline in astronauts’ functional capacity [1]. This deleterious effect is a consequence of several physiological and metabolic alterations in cardiovascular fitness level [2‒4], body composition and muscle strength [5, 6], bone mineral density (BMD) [7], and insulin sensitivity [8]. Exercise interventions used in the International Space Station (ISS) show protective effects leading to almost no loss in muscle mass [9] and less detrimental changes in BMD. However, duration of the exercise sessions is time-consuming (approximately 2 h per day) which impacts astronauts’ already busy schedules. In addition, large-size devices cannot fit in small capsular space vehicles for planned Mars missions. Changes in body composition and BMD [7] are mainly observed in the lower limbs, where muscle mass is greater [10]. A major reason for these detrimental changes is the microgravity environment which significantly reduces the frequency and magnitude of mechanical stress on the musculoskeletal system. Factors other than muscle unloading also contribute to these harmful changes, including reduced body fluid with central redistribution, oxidative stress, and radiation [11]. Physical exercise regimens have focused on the lower limb muscle group including a combination of resistive and aerobic types of exercises [1]. Resistance exercises were shown to improve muscle mass, muscle quality, and strength [12], whereas aerobic exercise imparts benefits for cardiovascular fitness [13].

Older adults undergoing long periods of physical inactivity or bed rest during hospitalization experience similar changes to those of astronauts on spaceflight missions [14]. Healthy older adults were reported to lose approximately 1 kg of lean tissue from the lower extremities along with a 16% decline in isokinetic knee extensor strength following 10 days of bed rest [15]. In addition, cardiovascular fitness level decreased by 12.3% following 14 days of bed rest [16, 17]. These are important clinical and public health issues, as the majority of hospitalized patients are older adults [18], whose number has doubled in the last 2 decades and continues to rise [19].

One challenge of human spaceflight research is to simulate the impact of microgravity on Earth to allow assessment of cost-effective and practical countermeasure interventions. This can be accomplished with long-duration head-down bed rest (HDBR), which proved to be a reliable simulation model [20]. HDBR studies offer a terrestrial analog for spaceflight where environmental variables can be controlled. The aim of this current study was to investigate the efficacy of exercise countermeasures for attenuation of musculoskeletal deconditioning, reductions in cardiovascular fitness level, and losses of muscle strength in healthy older participants during 14 days of HDBR. Changes in various blood parameters including hematology, selected hormones, neurotrophic factors, markers of inflammation, and bone turnover were also investigated. We hypothesized that both groups, with and without exercise, will experience detrimental body composition changes and losses in muscle strength and cardiovascular capacity following HDBR. However, these effects will be less pronounced in the intervention group following an exercise program.

Participants stayed a total of 26 days at the McConnell Centre for Innovative Medicine (CIM), Research Institute of the McGill University Health Centre (5 days of baseline, 14 days of HDBR, and 7 days of recovery). The details of the study have been described in a separate methodology article explaining the overall measurements and data collected throughout the study. In addition, the facility set up, the intervention, the recovery period, and the follow-up visits were detailed [1]. This trial was registered on ClinicalTrials.gov, NCT04964999. This study was a 2-arm randomized control trial where participants and assessors were not blinded.

A total of 219 volunteers expressed interest in participating (online suppl. material; for all online suppl. material, see https://doi.org/10.1159/000534063). Of these, 80 were deemed eligible, but 56 later declined. In the end, 24 participants were enrolled in the study (one was excluded due to group being full) and 20 participants completed the study in full. One participant dropped out on day 3 of HDBR, mainly for convenience reasons (hard to stay in position, difficulties to pass bowel movement, and required assistance for basic needs). Two participants were withdrawn from the study on day 3 of recovery due to the occurrence of atrial fibrillation. All measurements performed on them before the occurrence of the medical event were included in the analyses.

The exercise countermeasure has been detailed [1]. It consisted of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling as well as strength exercises for the lower and upper body. This resulted in a total of 60–75 min of physical exercise per day. All exercises were completed in a head-down tilt or horizontal position with available equipment as per a planned schedule. The intensity of the exercise countermeasures was individually adjusted according to participant performance and tolerance. The non-exercising group received physiotherapy consisting of passive range-of-motion exercises.

For the purpose of the standard measures, a venipuncture was performed at baseline, on day 8 of HDBR and on day one of the recovery period. Blood was collected into appropriate tubes and transported to the MUHC Clinical Laboratory for analysis. Blood was centrifuged, and serum and plasma were frozen in liquid nitrogen and stored at −80°C until analysis of the parameters listed in the supplementary material (Annex B).

Step-incremental exercise testing was conducted at baseline, and on either the first (in 4 participants) or second (n = 17 participants) day of the recovery period. The test consisted of 3-min baseline upright cycling at 15 W, followed by 15 W step-increments in work rate each minute until exhaustion. Participants were asked to maintain a consistent cadence of ∼70 rpm throughout the test, that was terminated once cadence fell below 65 rpm despite strong verbal encouragement. All exercise tests were performed in an environmentally controlled laboratory on an electrically braked cycle ergometer (Lode Corival CPET, Lode B.V., Groningen, NL, the Netherlands). Breath-by-breath oxygen uptake (V̇O_2peak) was measured using either a metabolic cart (Quark CPET, COSMED, Rome, IT, Italy) or a portable metabolic system (MetaMax 3B-R2^®), which were calibrated according to their respective manufacturer’s guidelines prior to each test. Breath-by-breath data were linearly interpolated to 1 Hz, and peak V̇O_2peak was computed as the highest 20-s moving average. In a subset of tests using the COSMED system, error in peak V̇O₂ was observed. Erroneous data points were corrected by using linear V̇O₂-work rate models to estimate the peak V̇O_2peak based on time to exhaustion. Personalized predictive models were developed for each individual using data collected with the MetaMax 3B-R2^® at another time point during the study. Subsequently, peak absolute V̇O₂ was normalized to participant’s body mass at the time of assessment.

During the baseline and the recovery period, weight was measured to the nearest 0.1 kg, after the overnight fast using a standing scale (Rice Lake Medical Scale, model: 250-10-2), whereas during the 14 days of bed rest, weight was measured using the bed scale to the nearest 0.5 kg (Stryker, model: Bari10A). Dual-energy X-ray absorptiometry (iDXA) scan (Lunar Prodigy, General Electric Healthcare, USA) was used for measuring body composition [21]. This noninvasive technique provides quantification of the major body compartments including bone mineral content and soft tissues, with the latter divided into fat and lean tissue [21]. This method presents a low within-subject coefficient of variation (±1.5%) is and strongly correlated with a four-compartment body composition model [22] and a multislice computed tomography. Whole-body soft lean tissue mass (hereafter called lean mass), fat mass, and bone density were quantified and leg soft lean mass which is defined from below the great trochanter area. Additionally, bone density of the hip and lumbar spine areas was measured. All participants performed this test at baseline and on day 3 of recovery. The DXA was calibrated on daily basis using a standard technique as provided by the manufacturer. Weight appearing in the body composition table is taken from the DXA scan.

The power output of the whole body was determined by using a countermovement jump [23]. It began with the hands being placed on the waist while maintaining an upright stance. This test was performed by rapidly squatting down and then pressing down firmly on the force plate to spring upward as high as possible. For this movement to be effective, the hands were firmly anchored on the hips to remove moments of inertia contributed by the arms swinging. The participant warmed up for the vertical jump by doing some light cardio and three sets of warm-up squats. After this, the participant was given two or three opportunities to practice countermovement jumps at 50% of their maximum effort to ensure that the proper technique had been understood. After the participants were fully prepared for the actual test, their body mass was determined by having them stand still for 30 s on a force plate. The participant then performed three maximum effort jumps with a 60- to 90-s rest period between each, or longer if they so desired. During the test, participants were encouraged to bring their heads as high as they could. Acceleration, velocity, and power profile for jumping, as well as flight height and fight time, were all calculated using the vertical ground reaction force measured during the jump test. In addition, participants’ schedules were designed to avoid a heavy meal within 1.5 h of the test, and strenuous physical activity in the 18 h leading up to the test.

A quantitative multi-joint muscle dynamometer (Biodex-system 3, Biodex Medical Systems Inc., NY, USA) was used to assess muscular strength of the thigh (quadriceps and hamstrings) muscles as well as the ankle muscles [24]. The participants were asked to perform maximal voluntary isometric contractions and isokinetic contractions to assess strength and power. Standardized verbal encouragement was provided throughout the test. Subjects got familiarized with the equipment and proper technique prior to the assessment. All participants performed this test at baseline and on day 2 and day 5 of recovery.

Data from twenty-two participants were included in the analyses (n = 11 in each study group) including those from the two participants who were withdrawn from the study recovery period due to atrial fibrillation. Variables were tested for normality distribution and baseline characteristics were all normally distributed. Independent t tests were performed to compare baseline characteristics between groups. A two-way repeated measures ANOVA was used to assess the effects of exercise intervention over time (within-group effect), group effect, and their interaction. If an interaction was observed, a pairwise comparison test was used to measure the change within groups. Data in text and tables are presented as means ± standard deviation. For all tests, p ≤ 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics software v29 for Mac (IBM, Inc., Chicago, IL, USA).

Participants’ baseline characteristics are presented in Table 1 disclosing no difference between control and exercise groups at baseline. Blood pressure, V̇O_2peak, body composition, and glucose levels show participants’ general health.

Total body mass showed a significant time effect reflecting an overall reduction during bed rest, but no group × time interaction, indicating no different changes between groups (Table 2). Total and leg lean masses showed a significant time effect reflecting an overall reduction but no group × time interaction, indicating no different changes between groups following the intervention. Total fat mass showed a significant time effect and group × time interaction following the intervention. Although both groups showed a decrease in total fat mass, exercise group had the highest change in magnitude.

There were no significant changes in peak acceleration and peak power before and after HDBR in either group (Table 3). However, peak velocity, flight height, and flight time are physically interrelated, and all significantly decreased with HDBR, without group × time interaction.

Muscle strength data are illustrated in Figure 1, panels 1A for knee and 1B for ankle. There was a significant reduction (time effect, p < 0.001) in isometric knee extension muscle strength following 14 days of bed rest (exercise group: −13%; control group: −16%) without interaction. Isokinetic knee extension was also significantly reduced (time effect, p = 0.001) following 14 days of bed rest (exercise group: −14%; control group: −9%) without interaction. No significant changes and interactions were observed in the isokinetic knee flexion (time effect, p = 0.1; group × time, p = 0.1) (Fig. 1a). The assessment of isometric ankle extension strength showed a significant time effect (p = 0.042) (exercise group: −7%; control group: −6%, no interaction). Isokinetic ankle plantar and ankle dorsal flexion strength did not change with bed rest in either group.

As shown in Figure 2, V̇O_2peak levels were maintained in the exercise group and decreased significantly in the control group following the intervention. A detailed description of the results is described in a separate paper [25].

As shown in Figure 3, there was a significant decrease in the total time (872 s at baseline; 416 s at recovery) of the tilt tolerance test (p < 0.0001) in both groups following 14 days of bed rest.

There was significant increase in both groups in white blood cells and C-reactive protein following the intervention (Table 4). In addition, a significant decrease in serum iron, total cholesterol, high-density lipoprotein-chol, low-density lipoprotein-chol, parathyroid hormone, and testosterone was observed in both groups following the intervention. The only group effects observed following the intervention are serum alanine transaminase and cortisol. Alanine transaminase levels increased in the exercise group, whereas they decreased in the control group. Cortisol levels were also increased in the exercise group and decreased significantly in the control group following the intervention. Future publications will present results of 4-week and 4-month follow-ups and will show more specific markers related to bone turnover, muscle protein synthesis, and inflammation.

This is the first Canadian aging and inactivity study using the HDBR model, funded by the Canadian Space Agency, jointly with the Canadian Institutes of Health Research and the Canadian Frailty Network. To our knowledge, it is also one of the few studies involving this age group. The present study was completed in 9 months including the 4-week and 4-month follow-up visits. Compared to other HDBR studies performed by the European Space Agency and NASA, the current study was completed in a record time as 20 out of 23 participants underwent the 26-day inpatient stay in less than 6 months. Furthermore, over this relatively short period, each participant underwent a total of 34 different types of measurements. Such intensity of tests made the study considerably complex, requiring a priori creation of a detailed schedule and a team of 32 employees from several backgrounds, as previously described. The involvement and commitment of the team contributed to contain dropouts in a single case.

One particularity of this HDBR study was that participants performed exercise sessions 3 times/day, which has never been accomplished previously in this type of study. We used a multimodal exercise program with substantial resistance training as described and incorporated a HIIT exercise protocol. All participants completed 100% of their exercise sessions except for two participants who each missed a single session.

Small but significant weight loss of about 1.1 kg (≅1.5%) occurred overall during bed rest. It is important to note that weight measurement using the bed scale has a 2–3% error, contrary to the standing weight scale that is less variable. Dietary energy was provided to match energy expenditure, estimated at bed rest onset using resting energy expenditure and adjusted for exercise three times during the HDBR period to avoid caloric deficit. Weight loss may be explained by decreased appetite and inability to meet energy needs by increasing food intake during bed rest [26].

Regarding body composition changes explaining the weight results, total and leg lean masses significantly decreased overall following the intervention, whereas total fat mass was significantly decreased solely in the exercise group. Of note, the small number of participants in each group and potential sex effects add to the variability in results and may have precluded finding an attenuation effect of exercise on lean mass loss in the exercise group. Other studies have shown a protective effect of exercise on maintaining lean mass following the intervention with a significant decrease in the control group [26‒28]. Further results regarding muscle mass measured using MRI will be published in the future showing a more accurate technique of measuring muscle mass compared to the DXA scan. Finally, total body fat mass decreased significantly more in the exercise group than in the control group following the intervention. Despite the weight-maintained diet and the attempt to match energy for each participant, the reduced total fat mass could be explained by the decrease in appetite following HIIT trainings [29]. A direct effect of exercise on fat mobilization is also another explanation in which through action of hormones and lipolytic factors could explain the significant loss of fat mass in the exercise group [30]. Regardless, some studies showed no differences in fat mass following 35 days of bed rest [31], while others showed similar changes observed in our study, where fat mass was decreased significantly in the exercise group [32].

On the jump test, both groups significantly decreased the peak velocity, flight height, and flight time. This reduction in the jump test of 18% and 11% in the control and exercise groups, respectively, has been observed in previous studies following 90 days of bed rest with or without a flywheel resistive exercise (−29.5% control group vs. −10.4% exercise group) [33]. Another horizontal 35-day bed rest showed similar decreases in jump height (−22%) following the intervention without any comparison with an exercise group. However, these changes observed during bed rest studies were conducted in a young population (20–35 years).

The assessment of isometric ankle and knee extension strength also showed a significant decrease of 14.2% in both groups following the intervention (p < 0.05). These changes have been observed in previous studies showing a decrease in knee extension strength (−8.6%) [34] following only 5 days of bed rest in adult men (35 years). These detrimental changes are emphasized after 10 and 14 days of bed rest dropping to 14.5% in the knee extension test [35, 36]. Several 20-day bed rest studies have demonstrated this loss to be heightened, reaching 18–20% [37, 38]. The changes reported in previous studies, albeit in a younger population (20–35 years), are of similar magnitude as our observations in the present study despite age differences.

Exercise seems to confer a protective effect on aerobic capacity following 14 days of bed rest [39]. In our study, the control group had significantly lower V̇O_2peak following 14 days of HDBR, whereas the exercise group maintained V̇O_2peak levels similar to baseline. These changes have been observed in previous studies. In a recent meta-analysis, the rate of detrimental changes seems to appear in the first 10 days of bed rest [17]. Of note, despite the protective effect of exercise observed in our study, low aerobic training does confer similar protective effect [39, 40]. However, increasing the intensity (75% of heart rate) after 18 days of bed rest and HIIT training performed daily seem to maintain the V̇O_2peak following the intervention [41, 42]. All previous HDBR studies have been done in a younger population (20–35 years). Despite the duration of the bed rest period, participants with a higher baseline aerobic capacity seem to have greater loss following the HDBR without exercise [17]. Older adults generally have lower fitness [43] but still experience large reductions in aerobic fitness (12%) after relatively short duration (10 days) of bed rest [16].

The total time during the orthostatic test (tilt test) was reduced by 52% following the intervention in both groups. Blood pressure of the participants dropped significantly (a decrease of 25 mm Hg in systolic blood pressure compared to baseline) and there was a significant increase in the heart rate (an increase of 40 BPM compared to baseline) leading the medical staff to stop the test to avoid any discomfort or loss of consciousness of the participants. These results are consistent with many others [44] and are explained in large part by a decrease in circulating blood volume [45]. In addition, baroreceptor dysfunction associated with bed rest has also been documented explaining the blood pressure drop [46]. Confirmation of the implication of these mechanisms in explaining the changes in tilt test tolerance time will be published in the future.

Many of the results reported above are in accordance with what has been previously found, including those of our blood parameters [47, 48]. The changes observed are small and probably without clinical relevance. Further details on specific measurements will be published in the future by each team individually, aiming to meet their specific objectives. Several upcoming publications from this study will be of value to provide further information to the changes observed, especially because it was conducted in an older population.

We felt compelled to report the challenges we faced, as there is a lack of these types of reports. Furthermore, they would be of benefit to other teams who plan to undertake bed rest studies, as members of the research team would feel more equipped to meet the challenges ahead. In our case, despite all the accommodations, team spirit, and the service provided, some participants still experienced challenges. Seven of them reported headaches, especially in the first few days of HDBR for which acetaminophen tablets were provided. In addition, 12 experienced difficulties voiding and passing a bowel movement, mainly in the first few days. Among these participants, five developed constipations, of which four were resolved by adapting the diet and one with laxative medication. Two participants had flu-like symptoms which were exacerbated in 6-degree HDBR making it more difficult to breathe, and saline nasal spray was provided for comfort. Two participants had dizziness at the end of the recovery period, with one being identified as vertigo. In this case, the medical doctor performed the Epley maneuver that resolved the issue. The other had mild dizziness on day 8 of HDBR that took a few weeks to resolve. These events have been reported in the past following prolonged bed rest periods [49]. However, in our case, it occurred in a short-duration HDBR-type study, but participants were on average older than in other studies.

One male participant went into urinary retention, requiring an indwelling catheter insertion and we later learned he had an enlarged prostate. This participant as well as another male, both in the control group, developed atrial fibrillation on day 3 of recovery that ended the study for them. Both were transferred to the emergency room of MUHC. One converted to sinus rhythm with a β-blocker, while the other required cardioversion. It remains unclear if bed rest was the cause of these arrhythmias as atrial fibrillation events increase with aging [50], but we are reporting them to create awareness.

Nurses experienced difficulties finding veins for blood tests during the 14-days HDBR for seven participants. Heating pads and in some cases the help of an anesthesiologist was needed, especially during the day of isotope infusion for protein breakdown measurements. A psychologist was needed only for one participant, where the issue was solved in a single visit. Appetite also decreased, and dieticians faced some difficulties reaching the daily nutritional recommendation. Protein milk and other alternatives were used to reach the aforementioned dietary requirements.

One of the major problems experienced during this study that needs to be taken into consideration in future studies is to avoid any intense physical testing on the first day of recovery (e.g., V̇O_2peak, Biodex, etc.). Some participants experienced nausea and were near fainting during the first day of recovery due to orthostatic hypotension. Lower body resistance exercise and balance exercises are also harder to perform on the first day of recovery. We recommend regular walking and ankle pumps exercises in the first few hours following standing up. Also, avoid turning their heads too fast and changing directions in the first few hours to avoid any falls. More bed rest studies in older adults are becoming a necessity to better understand the changes occurring in future astronauts as their age now averages 48 years old. Furthermore, due to the accelerating aging effects of bed rest it is an excellent model for understanding aging of body systems while unraveling consequences of prolonged hospitalization in older adults who undergo periods of inactivity.

We would like to thank the participants, members of the bed rest study staff, MUHC administrators, and technical research staff that made possible the achievement of this study. In addition to Dr. Valérie Gil and Miss kumudu Jinadasa from the Canadian Space Agency and all the contributors and the collaborators from all the research teams.

Ethical approval was obtained from the Research Institute of the McGill University Health Center. Reference number: 2021-7170. All participants had a written informed consent form prior to the start of the study.

None of the authors have conflicts of interest to declare.

This study was funded by the Canadian Space Agency, the Canadian Institutes of Health Research and the Canadian Frailty Network.

Study concept, design, and review of the manuscript: Guy Hajj-Boutros, Vita Sonjak, Andréa Faust, Eric T. Hedge, Carmelo Mastrandrea, Jean-Christophe Lagacé, Philippe St-Martin, Donya Naz Divsalar, Farshid Sadeghian, Stéphanie Chevalier, Teresa Liu-Ambrose, Andrew P. Blaber, Isabelle J. Dionne, Simon Duchesne, Richard Hughson, Saija Kontulainen, Olga Theo, and José A. Morais. Acquisition of data: Guy Hajj-Boutros, Vita Sonjak, Andréa Faust, Carmelo Mastrandrea, Eric T. Hedge, and José A. Morais. Analysis and interpretation of the data: Guy Hajj-Boutros, Vita Sonjak, Andréa Faust, Carmelo Mastrandrea, Eric T. Hedge, Donya Naz Divsalar, Farshid Sadeghian, and José A. Morais. Drafting of the manuscript and statistical analysis: Guy Hajj-Boutros, Vita Sonjak, and José A. Morais.

Data are not publicly available due to ethical reasons. Further inquiries can be directed to the corresponding author.