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.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Effects of Posture and Walking on Tibial Vascular Hemodynamics Before and After 14 Days of Head-Down Bed Rest.

Human skeletal hemodynamics remain understudied. Neither assessments in weight-bearing bones during walking nor following periods of immobility exist, despite knowledge of altered nutrient-artery characteristics after short-duration unloading in rodents. We studied 12 older adults (8 females, aged 59 ± 3 years) who participated in ambulatory near-infrared spectroscopy (NIRS) assessments of tibial hemodynamics before (PRE) and after (POST) 14 days of head-down bed rest (HDBR), with most performing daily resistance and aerobic exercise countermeasures during HDBR. Continual simultaneous NIRS recordings were acquired over the proximal anteromedial tibial prominence of the right lower leg and ipsilateral lateral head of the gastrocnemius muscle during supine rest, walking, and standing. During 10 minutes of walking, desaturation kinetics in the tibia were slower (time to 95% nadir values 125.4 ± 56.8 s versus 55.0 ± 30.1 s, p = 0.0014). Tibial tissue saturation index (TSI) immediately fell (-9.9 ± 4.55) and did not completely recover by the end of 10 minutes of walking (-7.4 ± 6.7%, p = 0.027). Upon standing, total hemoglobin (tHb) kinetics were faster in the tibia (p < 0.0001), whereas HDBR resulted in faster oxygenated hemoglogin (O2Hb) kinetics in both tissues (p = 0.039). After the walk-to-stand transition, changes in O2Hb (p = 0.0022) and tHb (p = 0.0047) were attenuated in the tibia alone after bed rest. Comparisons of NIRS-derived variables during ambulation and changes in posture revealed potentially deleterious adaptations of feed vessels after HDBR. We identify important and novel tibial hemodynamics in humans during ambulation before and after bed rest, necessitating further investigation. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

High-intensity exercise does not protect against orthostatic intolerance following bedrest in 55- to 65-yr-old men and women.

Prolonged bedrest provokes orthostatic hypotension and intolerance of upright posture. Limited data are available on the cardiovascular responses of older adults to head-up tilt following bedrest, with no studies examining the potential benefits of exercise to mitigate intolerance in this age group. This randomized controlled trial of head-down bedrest (HDBR) in 55- to 65-yr-old men and women investigated if exercise could avert post-HDBR orthostatic intolerance. Twenty-two healthy older adults (11 female) underwent a strict 14-day HDBR and were assigned to either an exercise (EX) or control (CON) group. The exercise intervention included high-intensity, aerobic, and resistance exercises. Head-up tilt-testing to a maximum of 15 minutes was performed at baseline (Pre-Bedrest) and immediately after HDBR (R1), as well as 6 days (R6) and 4 weeks (R4wk) later. At Pre-Bedrest, three participants did not complete the full 15 minutes of tilt. At R1, 18 did not finish, with no difference in tilt end time between CON (422 ± 287 s) and EX (409 ± 346 s). No differences between CON and EX were observed at R6 or R4wk. At R1, just 1 participant self-terminated the test with symptoms, while 12 others reported symptoms only after physiological test termination criteria were reached. Finishers on R1 protected arterial pressure with higher total peripheral resistance relative to Pre-Bedrest. Cerebral blood velocity decreased linearly with reductions in arterial pressure, end-tidal CO2, and cardiac output. High-intensity interval exercise did not benefit post-HDBR orthostatic tolerance in older adults. Multiple factors were associated with the reduction in cerebral blood velocity leading to intolerance.

Loss of cardiorespiratory fitness and its recovery following two weeks of head-down bed rest and the protective effects of exercise in 55- to 65-yr-old adults.

Cardiorespiratory fitness declines with age and this decline can be accelerated by inactivity and bed rest. Recovery of fitness is possible, but the timeline in 55- to 65-yr-old adults is unknown. Furthermore, the effectiveness of exercise to prevent deconditioning during bed rest is unexplored in this age group. Twenty-two adults (11 women, 59 ± 3 yr) completed 2 wk of strict 6° head-down bed rest (HDBR). Half of the participants performed approximately 1 h of daily exercises, including high-intensity interval cycling, aerobic cycling, and upper- and lower-body resistance training, whereas control participants were inactive. Step-incremental cycling tests to exhaustion were conducted pre-HDBR and at three times during the recovery phase (day 1 or 2, day 6, and 4 wk) to assess peak oxygen uptake (V̇o2). Peak V̇o2 was reduced in the control group throughout the first 6 days of recovery, but did return to pre-HDBR levels by the 4-wk recovery time point (interaction: P = 0.002). In the exercise group, peak V̇o2 was not different at any time point during recovery from pre-HDBR. Ventilatory threshold V̇o2 (interaction: P = 0.002) and heart rate at 15 W (interaction: P = 0.055) mirrored the changes in peak V̇o2 in each respective group. Overall, this study showed that approximately 1 h of daily exercise effectively protected 55- to 65-yr-old adults' cardiorespiratory fitness during 2 wk of HDBR. HDBR without exercise countermeasures caused substantial reductions in cardiorespiratory fitness, but fitness recovered within 4 wk of resuming daily activities. These findings highlight the importance of physical activity in late middle-age adults.NEW & NOTEWORTHY We report the complete time-course of cardiorespiratory fitness recovery back to baseline levels following 2 wk of head-down bed rest in 55- to 65-yr-old adults and found that multimodal training, consisting of high-intensity interval, aerobic and resistive exercises, performed throughout the 2 wk of head-down bed rest prevented reductions in cardiorespiratory fitness.

Hindlimb unloading in C57BL/6J mice induces bone loss at thermoneutrality without change in osteocyte and lacuno-canalicular network.

Impaired mechanical stimuli during hindlimb unloading (HLU) are believed to exacerbate osteocyte paracrine regulation of osteoclasts. We hypothesized that bone loss and deterioration of the osteocyte lacuno-canalicular network are attenuated in HLU mice housed at thermoneutrality (28 °C) compared with those housed at ambient temperature (22 °C). Following acclimatization, 20-week-old male C57BL/6J mice were submitted to HLU or kept in pair-fed control cages (CONT), for 5 days (5d) or 14d, at 22 °C or 28 °C. In the femur distal metaphysis, thermoneutral CONT mice had higher bone volume (p = 0.0007, BV/TV, in vivo µCT, vs. 14dCONT22) whilst osteoclastic surfaces of CONT and HLU were greater at 22 °C (5dCONT22 + 53 %, 5dHLU22 + 50 %, 14dCONT22 + 186 %, 14dHLU22 + 104 %, vs matching 28 °C group). In the femur diaphysis and at both temperatures, 14dHLU exhibited thinner cortices distally or proximally compared to controls; the mid-diaphysis being thicker at 28 °C than at 22 °C in all groups. Expression of cortical genes for proteolytic enzyme (Mmp13), markers for osteoclastogenic differentiation (MCSF, RANKL), and activity (TRAP, Ctsk) were increased following 22 °C HLU, whereas only Ctsk expression was increased following 28 °C HLU. Expression of cortical genes for apoptosis, senescence, and autophagy were not elevated following HLU at any temperature. Osteocyte density at the posterior mid-diaphysis was similar between groups, as was the proportion of empty lacunae (<0.5 %). However, analysis of the lacuno-canalicular network (LCN, fluorescein staining) revealed unstained areas in the 14dHLU22 group only, suggesting disrupted LCN flow in this group alone. In conclusion, 28 °C housing influences the HLU bone response but does not prevent bone loss. Furthermore, our results do not show osteocyte senescence or death, and at thermoneutrality, HLU-induced bone resorption is not triggered by osteoclastic activators RANKL and MCSF.

Implementation of exercise countermeasures during spaceflight and microgravity analogue studies: Developing countermeasure protocols for bedrest in older adults (BROA).

Significant progress has been made in the development of countermeasures to attenuate the negative consequences of prolonged exposure to microgravity on astronauts' bodies. Deconditioning of several organ systems during flight includes losses to cardiorespiratory fitness, muscle mass, bone density and strength. Similar deconditioning also occurs during prolonged bedrest; any protracted time immobile or inactive, especially for unwell older adults (e.g., confined to hospital beds), can lead to similar detrimental health consequences. Due to limitations in physiological research in space, the six-degree head-down tilt bedrest protocol was developed as ground-based analogue to spaceflight. A variety of exercise countermeasures have been tested as interventions to limit detrimental changes and physiological deconditioning of the musculoskeletal and cardiovascular systems. The Canadian Institutes of Health Research and the Canadian Space Agency recently provided funding for research focused on Understanding the Health Impact of Inactivity to study the efficacy of exercise countermeasures in a 14-day randomized clinical trial of six-degree head-down tilt bedrest study in older adults aged 55-65 years old (BROA). Here we will describe the development of a multi-modality countermeasure protocol for the BROA campaign that includes upper- and lower-body resistance exercise and head-down tilt cycle ergometry (high-intensity interval and continuous aerobic exercise training). We provide reasoning for the choice of these modalities following review of the latest available information on exercise as a countermeasure for inactivity and spaceflight-related deconditioning. In summary, this paper sets out to review up-to-date exercise countermeasure research from spaceflight and head-down bedrest studies, whilst providing support for the proposed research countermeasure protocols developed for the bedrest study in older adults.

Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission.

Spaceflight-induced bone losses have been reliably reproduced in Hind-Limb-Unloading (HLU) rodent models. However, a considerable knowledge gap exists regarding the effects of low-dose radiation and microgravity together. Ten-week-old male C57BL/6J mice, randomly allocated to Control (CONT), Hind-Limb Unloading (HLU), and Hind-Limb Unloading plus Irradiation (HLUIR), were acclimatized at 28 °C, close to thermoneutral temperature, for 28 days prior to the 14-day HLU protocol. HLUIR mice received a 25 mGy dose of X-ray irradiation, simulating 14 days of exposure to the deep space radiation environment, on day 7 of the HLU protocol. Trabecular bone mass was similarly reduced in HLU and HLUIR mice when compared to CONT, with losses driven by osteoclastic bone resorption rather than changes to osteoblastic bone formation. Femoral cortical thickness was reduced only in the HLUIR mice (102 µm, 97.5-107) as compared to CONT (108.5 µm, 102.5-120.5). Bone surface area was also reduced only in the HLUIR group, with no difference between HLU and CONT. Cortical losses were driven by osteoclastic resorption on the posterior endosteal surface of the distal femoral diaphysis, with no increase in the numbers of dead osteocytes. In conclusion, we show that low-dose radiation exposure negatively influences bone physiology beyond that induced by microgravity alone.

Human Secretory IgM: An Elusive Player in Mucosal Immunity.

Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a key role in establishing and promoting commensal gut tolerance in mice and humans. The true interactions between SIgMs and the microbiota remain controversial and we aim to consolidate current knowledge in this review. Through comprehensive examination of SIgMs and their corresponding B cell secretors in several different pathological immunological contexts, we review the presumed role of these molecules in gut tolerance, inflammatory bowel diseases, and lung immunity. As SIgMs harbor a mostly tolerogenic function, we posit that their inclusion in further immunological research is paramount.