Anatomy and histochemistry of hindlimb flight posture in birds. I. The extended hindlimb posture of shorebirds

Birds utilize one of two hindlimb postures during flight: an extended posture (with the hip and knee joints flexed, while the ankle joint is extended caudally) or a flexed posture (with the hip, knee, and ankle joints flexed beneath the body). American Avocets (Recurvirostra americana) and Black‐necked Stilts (Himantopus mexicanus) extend their legs caudally during flight and support them for extended periods. Slow tonic and slow twitch muscle fibers are typically found in muscles functioning in postural support due to the fatigue resistance of these fibers. We hypothesized that a set of small muscles composed of high percentages of slow fibers and thus dedicated to postural support would function in securing the legs in the extended posture during flight. This study examined the anatomy and histochemical profile of eleven hindlimb muscles to gain insight into their functional roles during flight. Contrary to our hypothesis, all muscles possessed both fast twitch and slow twitch or slow tonic fibers. We believe this finding is due to the versatility of dynamic and postural functions the leg muscles must facilitate, including standing, walking, running, swimming, and hindlimb support during flight. Whether birds use an extended or flexed hindlimb flight posture may be related to the aerodynamic effect of leg position or may reflect evolutionary history. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.     

Relative growth rates of limb muscles in the diprotodont marsupial, Setonix brachyurus

The fore- and hindlimb muscles of 12 Setonix brachyurus joeys, aged 5 to 175 days postpartum, and four adults were dissected out and weighed. Individual muscles and muscle groups were analysed for absolute and relative growth changes. From comprising almost 59% of the total limb musculature at birth the forelimb muscles finally constitute just over 9% in the adult; the hindlimb muscles start at just over 41% and end at almost 91%. In both limbs, the extensor actions predominate in the proximal limb segment because of their propulsive functions, whereas in the distal segment the flexor muscles tend to be the larger because of their shock-absorbing and spring functions. During growth of the fore-limb there is a relative increase in the size of latissimus dorsi and triceps brachii and a decrease in the distal segment muscles; in the hindlimb the gluteal and hamstring muscles increase at the expense of the distal segment muscles. Specializations for speed include long distal hindlimb segments and proximally located muscle bellies. The above findings reflect the adaptations and changing locomotor patterns from birth to adult in the Quokka.     

American Society of Biomechanics Journal of Biomechanics Award 2017: High-acceleration training during growth increases optimal muscle fascicle lengths in an avian bipedal model

Sprinters have been found to possess longer muscle fascicles than non-sprinters, which is thought to be beneficial for high-acceleration movements based on muscle force-length-velocity properties. However, it is unknown if their morphology is a result of genetics or training during growth. To explore the influence of training during growth, thirty guinea fowl (Numida meleagris) were split into exercise and sedentary groups. Exercise birds were housed in a large pen and underwent high-acceleration training during their growth period (age 4–14 weeks), while sedentary birds were housed in small pens to restrict movement. Morphological analyses (muscle mass, PCSA, optimal fascicle length, pennation angle) of a hip extensor muscle (ILPO) and plantarflexor muscle (LG), which differ in architecture and function during running, were performed post-mortem. Muscle mass for both ILPO and LG was not different between the two groups. Exercise birds were found to have ∼12% and ∼14% longer optimal fascicle lengths in ILPO and LG, respectively, than the sedentary group despite having ∼3% shorter limbs. From this study we can conclude that optimal fascicle lengths can increase as a result of high-acceleration training during growth. This increase in optimal fascicle length appears to occur irrespective of muscle architecture and in the absence of a change in muscle mass. Our findings suggest high-acceleration training during growth results in muscles that prioritize adaptations for lower strain and shortening velocity over isometric strength. Thus, the adaptations observed suggest these muscles produce higher force during dynamic contractions, which is beneficial for movements requiring large power outputs.     

Ultrastructural localization of lectin receptors on the bone-marrow sinusoidal endothelium of the rat

The purpose of this study was to estimate the absolute and relative masses of the three types of skeletal muscle fibers in the total hindlimb of the male Sprague-Dawley rat (Rattus norvegicus). For six rats, total body mass was recorded and the following weights taken from dissection of one hindlimb: 32 individual major muscles or muscle parts, remaining skeletal musculature (small hip muscles and intrinsic foot muscles), bone, inguinal fat pad, and skin. The fibers from the 32 muscles or muscle parts (which constituted 98% of the hindlimb skeletal muscle mass) were classified from histochemistry as fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), or slow-twitch oxidative (SO), and their populations were determined. Fiber cross-sectional areas from the same muscles were measured with a digitizer. Mass of each of the fiber types within muscles and in the total hindlimb was then calculated from fiber-type population, fiber-type area, and muscle-mass data. Skeletal muscle made up 71% of the total hindlimb mass. Of this, 76% was occupied by FG fibers, 19% by FOG fibers, and 5% by SO fibers. Thus, the FG fiber type is clearly the predominant fiber type in the rat hindlimb in terms of muscle mass. Fiber-type mass data are compared with physiological (blood flow) and biochemical (succinate dehydrogenase activities) data for the muscles taken from previous studies, and it is demonstrated that these functional properties are closely related to the proportions of muscle mass composed of the various fiber types.     

Wing and hindlimb myology of vultures and raptors (Accipitriformes) in relation to locomotion and foraging

Herein, we compare functional muscle properties among convergent forms of large, obligate avian scavengers. We performed quantitative analyses of all the muscle masses and cross‐sectional areas (CSA) of the wings and hindlimbs of five species from two families, Cathartidae (New World vultures; Cathartes aura and Vultur gryphus) and Accipitridae (Old World vultures and raptors; Gyps africanus, Aquila rapax, and Buteo lineatus). These species comprise two paraphyletic functional groups, raptors (Aquila and Buteo) and vultures (Gyps, Cathartes, and Vultur). Our ordination analyses based on all of the muscles of the wings, hindlimbs, and wing and hindlimb muscles combined produced patterns that appeared to be more related to phylogeny, with a hint of a functional signal in wing muscle CSA. However, when wing muscles were grouped according to their functional roles (upstroke, downstroke, and wing stabilization), the percentages of mass and CSA allocated to the upstroke and stabilizing muscles were 1.4–5% greater in the vultures than in the raptors. Conversely, when hindlimb muscles were grouped according to their roles in grasping and terrestrial locomotion, the percentages of mass and CSA allocated to grasping muscles were 5.9–14% greater in the raptors. Our results provide a baseline for future lines of inquiry aimed at understanding how muscle mass and CSA are affected differentially across locomotor modules, possibly in response to differential demands on wing and hindlimb function experienced by these disparate accipitriform clades.     

Pelvic and hindlimb myology of the basal archosaur Poposaurus gracilis (archosauria: Poposauroidea)

The discovery of a largely complete and well preserved specimen of Poposaurus gracilis has provided the opportunity to generate the first phylogenetically based reconstruction of pelvic and hindlimb musculature of an extinct nondinosaurian archosaur. As in dinosaurs, multiple lineages of basal archosaurs convergently evolved parasagittally erect limbs. However, in contrast to the laterally projecting acetabulum, or “buttress erect” hip morphology of ornithodirans, basal archosaurs evolved a very different, ventrally projecting acetabulum, or “pillar erect” hip. Reconstruction of the pelvic and hindlimb musculotendinous system in a bipedal suchian archosaur clarifies how the anatomical transformations associated with the evolution of bipedalism in basal archosaurs differed from that of bipedal dinosaurs and birds. This reconstruction is based on the direct examination of the osteology and myology of phylogenetically relevant extant taxa in conjunction with osteological correlates from the skeleton of P. gracilis. This data set includes a series of inferences (presence/absence of a structure, number of components, and origin/insertion sites) regarding 26 individual muscles or muscle groups, three pelvic ligaments, and two connective tissue structures in the pelvis, hindlimb, and pes of P. gracilis. These data provide a foundation for subsequent examination of variation in myological orientation and function based on pelvic and hindlimb morphology, across the basal archosaur lineage leading to extant crocodilians. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.     

Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice

Counteracting the atrophy of skeletal muscle associated with disuse has significant implications for minimizing the wasting and weakness in plaster casting, joint immobilization, and other forms of limb unloading, with relevance to orthopedics, sports medicine, and plastic and reconstructive surgery. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the loss of muscle mass and functional capacity in mice during 14 or 21 days of unilateral hindlimb casting. Twelve-week-old C57BL/10 mice were subjected to unilateral hindlimb plaster casting or served as controls. Mice received subcutaneous injections of saline or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n = 6-9) on days 0 and 7 and were tested for muscle function on day 14, or were treated on days 0, 7, and 14 and tested for muscle function on day 21. Hindlimb casting reduced muscle mass, fiber size, and function of isolated soleus and extensor digitorum longus (EDL) muscles (P < 0.05). PF-354 attenuated the loss of muscle mass, fiber size, and function with greater effects after 14 days than after 21 days of casting, when wasting and weakness had plateaued (P < 0.05). Antibody-directed myostatin inhibition therefore attenuated the atrophy and loss of functional capacity in muscles from mice subjected to unilateral hindlimb casting with reductions in muscle size and strength being most apparent during the first 14 days of disuse. These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for disuse atrophy especially within the first 2 wk of disuse.     

Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity

Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).     

Muscle-specific indices to characterise the functional behaviour of human lower-limb muscles during locomotion

The mechanical output of a muscle may be characterised by having distinct functional behaviours, which can shift to satisfy the varying demands of movement, and may vary relative to a proximo-distal gradient in the muscle-tendon architecture (MTU) among lower-limb muscles in humans and other terrestrial vertebrates. We adapted a previous joint-level approach to develop a muscle-specific index-based approach to characterise the functional behaviours of human lower-limb muscles during movement tasks. Using muscle mechanical power and work outputs derived from experimental data and computational simulations of human walking and running, our index-based approach differentiated known distinct functional behaviours with varying mechanical demands, such as greater spring-like function during running compared with walking; with anatomical location, such as greater motor-like function in proximal compared with the distal lower-limb muscles; and with MTU architecture, such as greater strut-like muscles fibre function compared with the MTU in the ankle plantarflexors. The functional indices developed in this study provide distinct quantitative measures of muscle function in the human lower-limb muscles during dynamic movement tasks, which may be beneficial towards tuning the design and control strategies of physiologically-inspired robotic and assistive devices.     

Functional roles of the leg muscles when pedaling in the recumbent versus the upright position

An understanding of the coordination of the leg muscles in recumbent pedaling would be useful to the design of rehabilitative pedaling exercises. The objectives of this work were to (i) determine whether patterns of muscle activity while pedaling in the recumbent and upright positions are similar when the different orientation in the gravity field is considered, (ii) compare the functional roles of the leg muscles while pedaling in the recumbent position to the upright position to the upright position and (iii) determine whether leg muscle onset and offset timing for recumbent and upright pedaling respond similarly to changes in pedaling rate. To fulfill these objectives, surface electromyograms were recorded from 10 muscles of 15 subjects who pedaled in both the recumbent and upright positions at 75, 90, and 105 rpm and at a constant workrate of 250 W. Patterns of muscle activation were compared over the crank cycle. Functional roles of muscles in recumbent and upright pedaling were compared using the percent of integrated activation in crank cycle regions determined previously for upright pedaling. Muscle onset and offset timing were also compared. When the crank cycle was adjusted for orientation in the gravity field, the activation patterns for the two positions were similar. Functional roles of the muscles in the two positions were similar as well. In recumbent pedaling, the uniarticular hip and knee extensors functioned primarily to produce power during the extension region of the crank cycle, whereas the biarticular muscles crossing the hip and knee functioned to propel the leg through the transition regions of the crank cycle. The adaptations of the muscles to changes in pedaling rate were also similar for the two body positions with the uniarticular power producing muscles of the hip and knee advancing their activity to earlier in the crank cycle as the pedaling rate increased. This information on the functional roles of the leg muscles provides a basis by which to form functional groups, such as power-producing muscles and transition muscles, to aid in the development of rehabilitative pedaling exercises and recumbent pedaling simulations to further our understanding of task-dependent muscle coordination.     

Skeletal muscle architecture of the rabbit hindlimb: functional implications of muscle design

The muscle-fiber architecture of 29 muscles from six rabbits (Oryctolagus cuniculus) was measured in order to describe the muscular properties of this cursorial animal, which possesses several specific skeletal adaptations. Several muscles were placed into one of four functional groups: hamstrings, quadriceps, dorsiflexors, or plantarflexors, for statistical comparison of properties between groups. Antagonistic groups (i.e., hamstrings vs. quadriceps or dorsiflexors vs. plantarflexors) demonstrated significant differences in fiber length, fiber length/muscle length ratio, muscle mass, pinnation angle, and number of sarcomeres in series (P less than .02). Discriminant analysis permitted characterization of the "typical" muscle belonging to one of the four groups. The quadriceps were characterized by their large pinnation angles and low fiber length/mass ratios, suggesting a design for force production. Conversely, the hamstrings, with small pinnation angles, appeared to be designed to permit large excursions. Similar differences were observed between plantarflexors and dorsiflexors, which have architectural features that suit them for force production and excursion respectively. Although these differences were not absolute, they represented clear morphological distinctions that have functional consequences.     

An electromyographic analysis of hindlimb function in Alligator during terrestrial locomotion

The neuromuscular control of the hindlimb of American alligators (Alligator mississippiensis) walking on a treadmill was analyzed using simultaneous electromyography (EMG) and cineradiography. EMG and kinematic data were integrated with myological information to discern the interplay of muscles mediating hip and knee movement during the high walk. Twelve muscles, subdivided into 23 individual heads, cross the hip joint of Alligator. Activity patterns of 12 heads of 11 hip muscles and one knee muscle were recorded and quantified. An additional five heads from four muscles were recorded in single individuals. During the stance phase, the caudofemoralis longus prevents hip flexion and actively shortens to retract the femur through an arc of 60–80°. At the same time, the adductor femoris 1 and pubo-ischio-tibialis control femoral abduction. The knee is extended 30–40° during stance by contraction of the femoro-tibialis internus. These stance phase muscles often produce discontinuous, periodic EMG signals within their normal burst profile. In late stance and early swing, the ilio-fibularis and the pubo-ischio-tibialis are responsible for flexing the knee. The limb is protracted by the pubo-ischio-femoralis internus 2 and pubo-ischio-femoralis externus 2, which flex the hip. The ilio-femoralis abducts the limb during swing to suspend it above the tread. The role of the ambiens 1, which is active in midswing, is unclear. The ilio-tibialis 2, flexor-tibialis externus and flexor-tibialis internus 2 yield sporadic, low amplitude EMGs; these muscles are recruited at a very low level, if at all, during the slow high walk. Although EMGs do not conclusively delineate muscle function, activity patterns are particularly helpful in elucidating the complex interaction of muscular heads in this system. J. Morphol. 234:197–212, 1997. © 1997 Wiley-Liss, Inc.     

Characterization of the passive mechanical properties of spine muscles across species

Passive mechanical properties differ between muscle groups within a species. Altered functional demands can also shift the passive force-length relationship. The extent that passive mechanical properties differ within a muscle group (e.g. spine extensors) or between homologous muscles of different species is unknown. It was hypothesized that multifidus, believed to specialize in spine stabilization, would generate greater passive tensile stresses under isometric conditions than erector spinae, which have more generalized functions of moving and stabilizing the spine; observing greater multifidus moduli in different species would strengthen this hypothesis. Permeabilized fibre bundles (n = 337) from the multifidus and erector spinae of mice, rats, and rabbits were mechanically tested. A novel logistic function was fit to the experimental data to fully characterize passive stress and modulus. Species had the greatest effect on passive muscle parameters with mice having the largest moduli at all lengths. Rats generated less passive stress than rabbits due to a shift of the passive force-length relationship towards longer muscle lengths. Rat multifidus generated slightly greater stresses than erector spinae, but no differences were observed between mouse muscles. The secondary objective was to determine the parameters required to simulate the passive force-length relationship. Experimental data were compared to the passive muscle model in OpenSim. The default OpenSim model, optimized for hindlimb muscles, did not fit any of the spine muscles tested; however, the model could accurately simulate experimental data after adjusting the input parameters. The optimal parameters for modelling the passive force-length relationships of spine muscles in OpenSim are presented.     

Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells

Atrophy of skeletal muscle leads to decreases in myofiber size and nuclear number; however, the effects of atrophic conditions on muscle precursor cells (MPC) are largely unknown. MPC lie outside myofibers and represent the main source of additional myonuclei necessary for muscle growth and repair. In the present study, we examined the properties of MPC after hindlimb suspension (HS)-induced atrophy and subsequent recovery of the mouse hindlimb muscles. We demonstrated that the number of MPC in atrophied muscles was decreased. RT-PCR analysis of cells isolated from atrophied muscles indicated that several mRNA characteristic of the myogenic program in MPC were absent. Cells isolated from atrophied muscles failed to properly proliferate and undergo differentiation into multinucleated myotubes. Thus atrophy led to a decrease in MPC and caused dysfunction in those MPC that remained. Upon regrowth of the atrophied muscles, these deleterious effects were reversed. Our data suggest that preventing loss or dysfunction of MPC may be a new pharmacological target during muscle atrophy. satellite cells; hindlimb suspension; proliferation; differentiation; myotubes     

New,puzzling insights from comparative myological studies on the old and unsolved forelimb/hindlimb enigma

Most textbooks and research reports state that the structures of the tetrapod forelimbs and hindlimbs are serial homologues. From this view, the main challenge of evolutionary biologists is not to explain the similarity between tetrapod limbs, but instead to explain why and how they have diverged. However, these statements seem to be related to a confusion between the serial homology of the vertebrate pelvic and pectoral appendages as a whole, and the serial homology of the specific soft‐ and hard‐tissue structures of the tetrapod forelimbs and hindlimbs, leading to an even more crucial and puzzling question being overlooked: why are the skeletal and particularly the muscle structures of the forelimb and hindlimb actually so strikingly similar to each other? Herein we provide an updated discussion of these questions and test two main hypotheses: (i) that the similarity of the limb muscles is due to serial homology; and (ii) that tetrapods that use hindlimbs for a largely exclusive function (e.g. bipedalism in humans) exhibit fewer cases of similarity between forelimbs and hindlimbs than do quadrupedal species. Our review shows that of the 23 arm, forearm and hand muscles/muscle groups of salamanders, 18 (78%) have clear ‘topological equivalents' in the hindlimb; in lizards, 14/24 (58%); in rats, 14/35 (40%); and in modern humans, 19/37 (51%). These numbers seem to support the idea that there is a plesiomorphic similarity and subsequent evolutionary divergence, but this tendency actually only applies to the three former quadrupedal taxa. Moreover, if one takes into account the total number of ‘correspondences’, one comes to a surprising and puzzling conclusion: in modern humans the number of forelimb muscles/muscle groups with clear ‘equivalents’ in the hindlimb (19) is substantially higher than in quadrupedal mammals such as rats (14), lizards (14) and even salamanders (18). These data contradict the hypothesis that divergent functions lead to divergent morphological structures. Furthermore, as we show that at least five of the 19 modern human adult forelimb elements that have a clear hindlimb ‘equivalent’ derive from embryonic anlages that are very different from the ones giving rise to their adult hindlimb ‘equivalents’, they also contradict the hypothesis that the similarity in muscle structures between the forelimb and hindlimb of tetrapods such as modern humans are due to their origin as serial homologues. This similarity is instead the result of phylogenetically independent evolutionary changes leading to a parallelism/convergence due to: (i) developmental constraints, i.e. similar molecular mechanisms are involved (particularly in the formation of the neomorphic hand), but this does not necessarily mean that similar anlages are used to form the similar adult structures; (ii) functional constraints, related to similar adaptations; (iii) topological constraints, i.e. limited physical possibilities; and even (iv) phylogenetic constraints, which tend to prevent/decrease the occurrence of new homoplasic similarities, but also help to keep older, ancestral homoplasic resemblances.     

Large-scale analysis of differential gene expression in the hindlimb muscles and diaphragm of mdx mouse

The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD), which is caused by the absence of dystrophin. Mdx limb muscles substantially compensate for the lack of dystrophin while the diaphragm is affected like DMD skeletal muscles. To understand better the complex cascade of molecular events leading to muscle degeneration and compensatory processes in mdx muscles, we analyzed alterations of gene expression in mdx hindlimb and diaphragm muscles as compared to their normal counterparts. The strategy was based on suppression subtractive hybridization followed by reverse Northern quantitative hybridization. Four subtracted/normalized libraries, containing cDNA clones up- or downregulated in mdx hindlimb muscles or diaphragm, were constructed and a total of 1536 cDNA clones were analyzed. Ninety-three cDNAs were found to be differentially expressed in mdx hindlimb muscles and/or diaphragm. They corresponded to 54 known genes and 39 novel cDNAs. The potential role of the known genes is discussed in the context of the mdx phenotype.     

Sarcomere length-joint angle relationships of seven frog hindlimb muscles.

The sarcomere length-joint angle relationship was measured in 7 different muscle-joint complexes (n = 43 muscles) of the frog hindlimb (Rana pipiens). Muscles studied included the cruralis, iliacus internus, gastrocnemius, gluteus magnus, gracilis major, semimembranosus and the semitendinosus. Muscle-joint complexes were mounted in a jig and submerged in chilled Ringer's solution. Joints were rotated throughout their range of motion, while sarcomere length was measured by laser diffraction. Muscles were then formalin fixed and architectural properties determined by microdissection of individual muscle fibers. Sarcomere length change per degree of joint rotation (dLs/d theta) ranged from a low of 3.7 nm/degree for the cruralis muscle acting at the knee to a high of 12.5 nm/degree for the semitendinosus muscle acting at the hip. Values for dLs/d theta were significantly different between all muscles (p < 0.001), and dLs/d theta values for muscles acting at the hip were significantly greater than those for muscles acting at the knee (p < 0.005). dLs/d theta was negatively correlated with fiber length, suggesting a balance between fiber length and moment arm in most muscle-joint systems. However, many exceptions to this generalization were noted. These data suggest that different muscle-joint systems are 'designed' for differential contribution of muscle force production to the joint torque profile. The low variability of these data also suggests that sarcomere number is tightly regulated in these muscle-joint systems but not simply as a result of the total in vivo muscle excursion.     

Effects of Resveratrol on the Recovery of Muscle Mass Following Disuse in the Plantaris Muscle of Aged Rats

Aging is associated with poor skeletal muscle regenerative ability following extended periods of hospitalization and other forms of muscular disuse. Resveratrol (3,5,4’-trihydroxystilbene) is a natural phytoalexin which has been shown in skeletal muscle to improve oxidative stress levels in muscles of aged rats. As muscle disuse and reloading after disuse increases oxidative stress, we hypothesized that resveratrol supplementation would improve muscle regeneration after disuse. A total of thirty-six male Fisher 344 × Brown Norway rats (32 mo.) were treated with either a water vehicle or resveratrol via oral gavage. The animals received hindlimb suspension for 14 days. Thereafter, they were either sacrificed or allowed an additional 14 day period of cage ambulation during reloading. A total of six rats from the vehicle and the resveratrol treated groups were used for the hindlimb suspension and recovery protocols. Furthermore, two groups of 6 vehicle treated animals maintained normal ambulation throughout the experiment, and were used as control animals for the hindlimb suspension and reloading groups. The data show that resveratrol supplementation was unable to attenuate the decreases in plantaris muscle wet weight during hindlimb suspension but it improved muscle mass during reloading after hindlimb suspension. Although resveratrol did not prevent fiber atrophy during the period of disuse, it increased the fiber cross sectional area of type IIA and IIB fibers in response to reloading after hindlimb suspension. There was a modest enhancement of myogenic precursor cell proliferation in resveratrol-treated muscles after reloading, but this failed to reach statistical significance. The resveratrol-associated improvement in type II fiber size and muscle mass recovery after disuse may have been due to decreases in the abundance of pro-apoptotic proteins Bax, cleaved caspase 3 and cleaved caspase 9 in reloaded muscles. Resveratrol appears to have modest therapeutic benefits for improving muscle mass after disuse in aging.