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Effects of simulated increased gravity on the rate of aging of rats: implications for the rate of living theory of aging.

Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g. by placement in the cold) is usually accompanied by general homeostatic disturbance and stress. The present study was based on the finding that rats exposed to slightly increased gravity are able to adapt with little chronic stress but at a higher level of basal metabolic expenditure (increased 'rate of living'). The rate of aging of 17-mth-old rats that had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 mth was larger than of controls as shown by apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration (reduced 'efficiency': 20% larger ADP: 0 ratio, P less than 0.01; reduced 'speed': 8% lower respiratory control ratio, P less than 0.05). On the other hand, steady-state food intake per day per kg body weight, which is presumably proportional to 'rate of living' or specific basal metabolic expenditure, was about 18% higher than in controls (P less than 0.01) after an initial 2-mth adaptation period. Finally, though half of the centrifuged animals lived only a little shorter than controls (average about 343 vs. 364 days on the centrifuge, difference statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for controls, computed from onset of centrifugation, or 11% shorter (P less than 0.01). Therefore, these results show that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Aging↗

Gravity as an obligatory factor in normal higher plant growth and development.

Gravity may influence different aspects of plant activity. The present report deals with two questions: gravity as an ecological factor determining spatial orientation of plant growth; and second, a possible requirement for gravity in the process of normal growth, morphogenesis and generative development of plants.

Arabidopsis↗

Compensation of translational and rotational perturbations in human posture: stabilization of the centre of gravity.

EMG responses in the leg muscles, head acceleration and joint movements induced by dorsiflexing rotation of the ankle have been analysed. Perturbations were induced while subjects were standing on a platform with the ankle joints co-linear with the axis of rotation or while standing above the axis (between 5 and 25 cm), which introduced an additional translational component to the displacement. The former condition was followed by a monosynaptic gastrocnemius reflex potential and a late tibialis anterior activation (latency about 100 ms); in the latter condition the monosynaptic reflex response became smaller and a longer latency gastrocnemius response (latency about 70 ms) appeared, the strength and duration of which increased in parallel with the translational component, while the amplitude of the tibialis anterior activity decreased. Neither vestibulospinal nor muscle proprioceptive mechanisms can solely account for this effect as the biomechanical parameters were little changed in the different conditions. It is suggested that the controlled variable in the investigated task is to hold the bodies' centre of gravity over the feet which makes the change in the pattern meaningful: pure dorsiflexion of the feet is followed by a backwards sway of the body, thus a tibialis anterior activation is functionally essential to hold the centre of gravity over the feet. A backwards translation of the feet withdraws the supporting surface, thus a gastrocnemius activation is needed to restore the centre of gravity over the feet. The inhibition of the monosynaptic reflex with increasing translation is suggested to arise from a reciprocal modulation of mono- and polysynaptic gastrocnemius reflex responses.

Acceleration↗

Flexion-relaxation response to gravity.

The objective of this report was to study the influence of the orientation of gravitational loading on the behavior of anterior and posterior trunk muscles during anterior trunk flexion-extension. Participants (N=13) performed five (5) cycles of trunk flexion-extension while standing with gravity parallel to the body axis and five (5) cycles while in the supine condition (e.g. sit-ups) with gravity perpendicular to the body axis. Surface electromyographic (EMG) patterns from lumbar paraspinal, rectus abdominis, external oblique, rectus femoris, semimembranosis, and biceps femoris muscles were analyzed during each condition. EMG signals were synchronized with lumbar flexion and trunk inclination angles. Flexion-extension from the standing position resulted in a myoelectric silent period of the lumbar posterior muscles (e.g. flexion-relaxation phenomena (FRP)) as well as the hamstring muscles through deep angles during which activity was observed in abdominal muscles. Flexion-extension during sit-ups, however, resulted in a myoelectric silent period of the abdominal muscles and the quadriceps through deep angles during which the lumbar posterior muscles were active. In this condition, the FRP was not observed in posterior muscles. The new findings demonstrate the profound impact of the orientation of the gravity vector on the FRP, the abdominal muscles reaction to gravitational loads during sit-ups and its relationships with lumbar antagonists and thigh musculature. The new findings suggest that gravitational moments requirements dominate the FRP through the prevailing kinematics, load sharing and reflex activation-inhibition of muscles in various conditions. Lumbar kinematics or fixed sensory motor programs by themselves, however, are not the major contributor to the FRP. The new findings improve our insights into spinal biomechanics as well as understanding and evaluating low back disorders.

Adolescent↗

Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei.

Mice lacking normal vestibular gravity reception show altered homeostatic, circadian and autonomic responses to hypergravity (+G) exposure. Using c-Fos as a marker of neuronal activation, the current study identifies CNS nuclei that may be critical for initiating and integrating such responses to changes in vestibular signaling. This experiment utilized the mutant C57BL/6JEi-het mouse (het), which lacks macular otoconia and thus gravity receptor function. Following 2 h of 2G (2x Earth's gravity) exposure (via centrifugation) the neuronal responses of the het mice were compared with wildtype mice similarly exposed to 2G, as well as het and wildtype 1G controls. Wildtype mice exposed to 2G demonstrated robust c-Fos expression in multiple autonomic, hypothalamic and limbic nuclei, including: the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamus, dorsomedial hypothalamus, arcuate, suprachiasmatic hypothalamus, intergeniculate leaflet, dorsal raphe, parabrachial and locus coeruleus. The het mice exposed to 2G demonstrated little to null c-Fos expression in these nuclei with a few exceptions and, in general, a similar pattern of c-Fos to 1G controls. Data from this study further support the existence of a complex and extensive influence of the neurovestibular system on homeostatic, circadian and possibly autonomic regulatory systems.

Animals↗

Computational predictions of pulmonary blood flow gradients: gravity versus structure.

A computational model of blood flow through the human pulmonary arterial tree has been developed to investigate the mechanisms contributing to regional pulmonary perfusion in the isolated network when the lung is in different orientations. The arterial geometric model was constructed using a combination of computed tomography and a volume-filling branching algorithm. Equations governing conservation of mass, momentum, and vessel distension, incorporating gravity, were solved to predict pressure, flow, and vessel radius. Analysis of results in the upright posture, with and without gravity, and in the inverted, prone, and supine postures reveals significant flow heterogeneity and a persistent decrease in flow in the cranial and caudal regions for all postures suggesting that vascular geometry makes a major contribution to regional flow with gravity having a lesser role. Results in the isolated arterial tree demonstrate that the vascular path lengths and therefore the positioning of the pulmonary trunk relative to the rest of the network play a significant role in the determination of flow.

Algorithms↗

Gravity, blink rate, and lacrimal drainage capacity.

PURPOSE: To investigate the influence of gravity and blink rate on lacrimal drainage capacity and to learn whether lacrimal pump function can be measured with the drop test. METHODS: The drop test for lacrimal drainage capacity was performed in 20 test subjects, aged 12 to 30 years. Drops of a known volume of lukewarm saline solution were repeatedly instilled in the tear film for 3 minutes. Excessive saline solution was then removed, and the volume drained by the lacrimal passages was calculated. The drop test was performed both with the nasolacrimal duct in a 45-degree position and with the nasolacrimal duct in a horizontal position. The drop test was performed two times in each position, with the individual reading and not reading. A lower blink rate was induced by reading. RESULTS: There was a high correlation between blink rate and lacrimal drainage when the nasolacrimal duct was in a horizontal position. The volume drained with each blink was approximately 2 microliters. However, when gravity acted upon the fluid in the lacrimal sac-nasolacrimal duct in the direction of the tear flow, the lacrimal drainage capacity showed a significant but variable increase, and there was no significant correlation between blink rate and lacrimal drainage capacity. CONCLUSIONS: Lacrimal drainage capacity in young individuals was significantly affected by both blink rate and gravity. Lacrimal pump function can be measured quantitatively with the drop test.

Administration, Topical↗

An algorithm for determining gravity line location from posturographic recordings.

In posturographic recordings, the center of pressure (COP) displacement does not accurately reflect migration of the gravity line (GL), the vertical line passing through the body's center of gravity, COG. Since the horizontal ground reaction force, Fx, is proportional to the horizontal acceleration of the COG its second integral does represent the horizontal position of the gravity line (GLP). However, the initial constants of integration, initial velocity and position, are not known. In this note, a technique for estimating these integration constants is suggested: zero-point-to-zero-point integration. This method is based on a postulation that when Fx = 0, the GLP and COP coincide. By integrating Fx from one zero point to another zero point, both the instantaneous GLP and its velocity are determined. A validation of the suggested algorithm was performed using optical methods to determine the GLP during a one legged standing tasks. Cross-correlation values of GLP determined via videography and the suggested algorithm ranged from 0.79 to 0.96. These results suggest that the zero-point-to-zero-point-integration is an acceptable technique for determining GLP from posturographic recordings.

Algorithms↗

The face inversion effect in microgravity: is gravity used as a spatial reference for complex object recognition?

Complex objects are better recognized under a specific orientation. When presented upside down, a face, even very familiar, is recognized with greater difficulty than when presented upright ("Inversion effect"). Up to now it was not possible to decide whether the direction provided by gravity or the one provided by the retina and the body constitutes the spatial reference involved in this "Inversion effect". Three cosmonautes learned photographed faces on the ground and had to recognize them both on ground and on flight. Other photographed faces were learned in flight and where presented for recognition on flight. Results show that the Inversion effect is still present on flight for faces that have been learned on ground as well as for those learned on flight. Persistence of the inversion effect in 0-G shows that gravity is not involved as a spatial reference in recognition of faces. Learning and recognition performances of faces learned in flight were significantly lower than performances for faces learned on ground. A possible role of gravity in configural processing, but not in the Inversion effect, is suggested.

Aerospace Medicine↗

Arm end-point trajectories under normal and micro-gravity environments.

The purpose of the present experiment was to study the way in which the CNS represents gravitational force during vertical arm pointing movements. Movements in upward and downward directions were executed by two cosmonauts in normal-gravity and weightlessness. Analyses focused upon finger kinematics in the sagittal plane. In normal-gravity, downward direction movements showed smaller curvatures and greater relative times to peak velocity (AT/MT) when compared with upward direction movements. Data from the weightlessness experiments showed that whilst downward movements decreased their curvature during space flight, curvatures of upward movements changed slightly. Furthermore, AT/MT was modified during the first days in micro-gravity for both directions, recovering, however, to pre-flight values after 18 days in space. Results from the present study, provide evidence that gravitational force is centrally treated constituting an important component of the motor plan for vertical arm movements.

Aerospace Medicine↗

Skeletogenesis in sea urchin larvae under modified gravity conditions.

From many points of view, skeletogenesis in sea urchins has been well described. Based on this scientific background and considering practical aspects of sea urchin development (i.e. availability of material, size of larvae, etc.), we wanted to know whether orderly skeletogenesis requires the presence of gravity. The objective has been approached by three experiments successfully performed under genuine microgravity conditions (in the STS-65 IML-2 mission of 1994; in the Photon-10 IBIS mission of 1995 and in the STS-76 S/MM-03 mission of 1996). Larvae of the sea urchin Sphaerechinus granularis were allowed to develop in microgravity conditions for several days from blastula stage onwards (onset of skeletogenesis). At the end of the missions, the recovered skeletal structures were studied with respect to their mineral composition, architecture and size. Live larvae were also recovered for post-flight culture. The results obtained clearly show that the process of mineralisation is independent of gravity: that is, the skeletogenic cells differentiate correctly in microgravity. However, abnormal skeleton architectures were encountered, particularly in the IML-2 mission, indicating that the process of positioning of the skeletogenic cells may be affected, directly or indirectly, by environmental factors, including gravity. Larvae exposed to microgravity from blastula to prism/early pluteus stage for about 2 weeks (IBIS mission), developed on the ground over the next 2 months into normal metamorphosing individuals.

Animals↗

Metabolic adaptation to long term changes in gravity environment.

Biochemical analyses of the brain of Cichlid fish larvae, exposed during their very early development for 7 days to an increased acceleration of 3g (hyper-gravity), revealed a decrease in brain nucleoside diphosphate kinase (NDPK) as well as creatine kinase (BB-CK) activity. Using high performance liquid chromatography (HPLC) the concentrations of adenine nucleotides (AMP, ADP, ATP), phospliocreatine (CP), as well as of nicotineamide adenine dinucleotides (NAD, NADP) were analyzed in the brain of hyper-g exposed larvae vs. 1g controls. A slight reduction in the total adenine nucleotides (TAN) as well as the adenylate energy charge (AEC) was found. In parallel a significant increase in the NAD concentration and a corresponding decrease in NADP concentration occurred in larva's hyper-g brains vs. 1 g controls. These results give further evidence for an Influence of gravity on cellular level and furthermore contribute to a clarification of the cellular signal-response chain for gravity perception.

Adenine Nucleotides↗

Nonequilibrium / nonlinear chemical oscillation in the virtual absence of gravity.

The Belousov-Zhabotinsky (BZ) reactions were used as typical examples of a nonlinear system far from equilibrium in connection with biological evolution. The virtual absence of gravity in the present work was given from the free-fall facility of Japan Microgravity Center (JAMIC) in Hokkaido. The reaction solution of BZ reaction was composed of bromate in sulfuric acid, 1,4-cyclohexanedione and ferroin to visualize the time development of patterns of chemical oscillations in the reaction-diffusion system. It is a bubble-free constitution in the aging of the reaction. Therefore, the setup constructed to collect image data via CCD cameras was simplified. The operation sequences of necessary devices were comprised of simple solid state relays which were started by a command from the operation room of JAMIC. The propagation profile of chemical patterns under microgravity of 10(-5) g was collected as image data for 9.8 s, and processed by a software of STM-STS2. In the aqueous solutions, propagation velocity of chemical patterns under microgravity was decreased to 80.9 % of that under normal gravity, owing to suppression of convection. On the other hand, in gel matrix, gravity did not influence the propagation velocity.

Bromates↗

Plasma membrane NADH oxidase of maize roots responds to gravity and imposed centrifugal forces.

NADH oxidase activities measured with excised roots of dark-grown maize (Zea mays) seedlings and with isolated plasma membrane vesicles from roots of dark-grown maize oscillated with a regular period length of 24 min and were inhibited by the synthetic auxin 2,4-dichlorophenoxyacetic [correction of dichorophenoxyacetic] acid. The activities also responded to orientation with respect to gravity and to imposed centrifugal forces. Turning the roots upside down resulted in stimulation of the activity with a lag of about 10 min. Returning the sections to the normal upright position resulted in a return to initial rates. The activity was stimulated reversibly to a maximum of about 2-fold with isolated plasma membrane vesicles, when subjected to centrifugal forces of 25 to 250 x g for 1 to 4 min duration. These findings are the first report of a gravity-responsive enzymatic activity of plant roots inhibited by auxin and potentially related to the gravity-induced growth response.

2,4-Dichlorophenoxyacetic Acid↗

Morphogenesis and gravity in a whole amphibian embryo and in isolated blastomeres of sea urchins.

Fertilization and subsequent embryogenesis of newts occurred normally under microgravity in two Astronewt flight experiments. By accumulation of the results from the amphibian flight experiments including 'Astronewt', it is considered that gravity has rather small effects on the early development of amphibian eggs. However, some temporary abnormalities, which recover in the course of the further developmental process, have been observed. Some regulations may occur in whole embryos. For a thorough knowledge about the role of gravity in morphogenesis, we need to investigate the gravitational effects on a single cell in a whole embryo. We propose a new experimental system with sea urchin embryos and micromeres for further studies at a cellular level of the effects of gravity on morphogenesis.

Amphibians↗

Is skeletal muscle ready for long-term spaceflight and return to gravity?

It is now clear that prevention of muscle debilitation during spaceflight will require a broader approach than simple exercise aimed at strengthening of the muscle fibers. The levels of several hormones and receptors are altered by unloading and must be returned to homeostasis. Pharmacotherapy and gene transfer strategies to raise the relative level of structural proteins may minimize the problems faced by astronauts in readapting to Earth-gravity. Up to now, we have only minimally exploited microgravity for advancing our understanding of muscle biology. A research laboratory in the space station with a centrifuge facility (gravity control) is essential for conducting basic research in this field. Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance and atrophy of muscle. Understanding the relation between blood flow and interstitial edema and between workload and subsequent structural failure are but two important problems that require serious attention. The roles of hormones and growth factors in regulating gene expression and their microgravity-induced altered production are other urgent issues to pursue. These types of studies will yield information that advances basic knowledge of muscle biology and offers insights into countermeasure design. This knowledge is likely to assist rehabilitation of diseased or injured muscles in humans on Earth, especially individuals in the more vulnerable aging population and persons participating in strenuous sports. Will the skeletal muscle system be prepared for the increased exposure to microgravity and the return to gravity loading without injury when space station is operational? The answer depends in large part on continued access to space and funding of ground-based models and flight experiments. The previous two decades of spaceflight research have described the effects of microgravity on multiple systems. The next generation of experiments promises to be even more exciting as we are challenged to define the cellular and molecular mechanisms of microgravity-induced changes.

Animals↗

Microchip separations in reduced-gravity and hypergravity environments.

Microfabricated fluidics technology, e.g., lab-on-a-chip devices, offers many attractive features for performing chemistry and biochemistry on space-based platforms. We have constructed a portable, battery-operated microfluidic platform that was tested under reduced gravity and hypergravity conditions that would be experienced in space flight and launch. This device consisted of a microchip, microchip holder, two 0-8-kV high-voltage power supplies, a high-voltage switch, a solid-state diode-pumped green laser, an optical train, a channel photomultiplier, and an inertial mass measurement unit all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. The unit was tested on NASA's reduced gravity research aircraft at gravity levels that are relevant to NASA's intended use of bioreporter-based microchips for environmental monitoring of space and planetary environments on manned and unmanned spacecraft. Over the course of two flights, 834 fast electrophoretic separations of four amino acids were performed under a variety of gravitational environments including zero-g, Martian-g, lunar-g, and approximately 1.8-g. All separations were performed in less than 12 s and automatically analyzed. After correction with an internal migration standard, the migration time reproducibilities were all <1% relative standard deviation.

Journal Article↗

Evidence for gravity's influence on molecules at a solid-solution interface.

Yoshimoto et al. [Anal. Chem. 2002, 74, 4306-4309] reported that a quartz crystal microbalance or QCM changed its response to sucrose solutions according to its angle of immersion. The effect was tentatively attributed to gravity-caused stress on the viscous interface between the oscillator and the bulk solution. The present work reports results from QCM experiments carried out so that any effect of gravity on the interfacial region would be magnified. This permitted use of a lower-frequency, less-sensitive QCM. Molecules of DNA were tethered to a functionalized QCM surface and then extended in steps, via sandwich hybridization, to produce DNA of uniform and known length. This feature allowed both the effect of QCM immersion angle and the relationship between frequency and molecular length to be investigated simultaneously. Comparison of acoustic wave damping at 0 degrees and 180 degrees immersion angles offers compelling evidence that the interfacial region expands when the active face of the QCM is down and contracts when it is up. This is apparently a consequence of the interfacial region being more dense than the bulk solution. The results are consistent with (a) slow gravity-driven movement of molecules away from a down-facing QCM, (b) rapid hybridization-driven movement away from an up-facing QCM, and (c) a QCM frequency response that decreases according to a simple exponential function of the tethered molecules' radius of gyration.

Acoustics↗