Spinal Muscular Atrophy

A growing body of evidence supports the use of moderate blood flow restriction (BFR) combined with lowload resistance exercise to enhance hypertrophic and strength responses in skeletal muscle. Research also suggests that BFR during low-workload aerobic exercise can result in small but significant morphological and strength gains, and BFR alone may attenuate atrophy during periods of unloading. While BFR appears to be beneficial for both clinical and athletic cohorts, there is currently no common consensus amongst scientists and practitioners regarding the best practice for implementing BFR methods. If BFR is not employed appropriately, there is a risk of injury to the participant. It is also important to understand how variations in the cuff application can affect the physiological responses and subsequent adaptation to BFR training. The optimal way to manipulate acute exercise variables, such as exercise type, load, volume, inter-set rest periods and training frequency, must also be considered prior to designing a BFR training programme. The purpose of this review is to provide an evidence-based approach to implementing BFR exercise. These guidelines could be useful for practitioners using BFR training in either clinical or athletic settings, or for researchers in the design of future studies investigating BFR exercise.

To establish the prevalence of sarcopenia in older Americans and to test the hypothesis that sarcopenia is related to functional impairment and physical disability in older persons. DESIGN: Cross-sectional survey. SETTING: Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III). PARTICIPANTS: Fourteen thousand eight hundred eighteen adult NHANES III participants aged 18 and older.

For years enhancement of a patientÕs level of physical fitness has been an important goal in rehabilitation treatment in chronic low back pain (CLBP), based on the hypothesis that physical deconditioning contributes to the chronicity of low back pain. However, whether this hypothesis in CLBP holds is not clear. In this paper, possible mechanisms that contribute to the development of physical deconditioning in CLBP, such as avoidance behaviour and suppressive behaviour, are discussed. The presence of both deconditioning-related physiological changes, such as muscle atrophy, changes in metabolism, osteoporosis and obesity as well as deconditioning related functional changes, such as a decrease in cardiovascular capacity, a decrease in muscle strength and impaired motor control in patients with CLBP are discussed. Results of studies on the level of physical activities in daily life (PAL) and the level of physical fitness in patients with CLBP compared to healthy controls were reviewed. In studies on PAL results that were either lower or comparable to healthy subjects were found. The presence of disuse (i.e., a decrease in the level of physical activities in daily life) in patients with CLBP was not confirmed. The inconclusive findings in the papers reviewed may partly be explained by different measurement methods used in research on PAL in chronic pain. The level of physical fitness of CLBP patients also appeared to be lower or comparable to the fitness level of healthy persons. A discriminating factor between fit and unfit patients with back pain may be the fact that fit persons more frequently are still employed, and as such may be involved more in physical activity. Lastly some suggestions are made for further research in the field of disuse and deconditioning in CLBP.

Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder characterized by degeneration of lower motor neurons, leading to progressive paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome 5q13, where large-scale deletions have been reported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is either lacking or interrupted in 226 of 229 patients, and patients retaining this gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.

To determine: 1) whether sarcopenic-obesity is a stronger predictor of cardiovascular disease (CVD) than either sarcopenia or obesity alone in the elderly, and 2) whether muscle mass or muscular strength is a stronger marker of CVD risk. Prospective cohort study. Participants included 3366 community-dwelling older (>or= 65 years) men and women who were free of CVD at baseline. Waist circumference (WC), bioimpedance analysis, and grip strength were used to measure abdominal obesity, whole-body muscle mass, and muscular strength, respectively. Subjects were classified as normal, sarcopenic, obese, or sarcopenic-obese based on measures of WC and either muscle mass or strength. Participants were followed for 8 years for CVD development and proportional hazard regression models were used to compare risk estimates for CVD in the four groups after adjusting for age, sex, race, income, smoking, alcohol, and cognitive status. Compared with the normal group, CVD risk was not significantly ...

Hamstring strain injuries are amongst the most common and problematic injuries in a wide range of sports that involve high speed running. The comparatively high rate of hamstring injury recurrence is arguably the most concerning aspect of these injuries. A number of modifiable and nonmodifiable risk factors are proposed to predispose athletes to hamstring strains. Potentially, the persistence of risk factors and the development of maladaptations following injury may explain injury recurrence. Here, the role of neuromuscular inhibition following injury is discussed as a potential mechanism for several maladaptations associated with hamstring re-injury. These maladaptations include eccentric hamstring weakness, selective hamstring atrophy and shifts in the knee flexor torque-joint angle relationship. Current evidence indicates that athletes return to competition after hamstring injury having developed maladaptations that predispose them to further injury. When rehabilitating athletes to return to competition following hamstring strain injury, the role of neuromuscular inhibition in re-injury should be considered.

Introduction: There is no curative treatment for the common motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Nevertheless, there is an increasing volume of published studies. This review assesses the current evidence for treatment of these conditions. Sources of data: Primarily, the systematic reviews of the Cochrane Collaboration, with additional reference to other systematic reviews and online sites. Areas of agreement: Riluzole remains the only medication with demonstrated efficacy and regulatory approval for the treatment of ALS. Areas of controversy, growing points and areas timely for developing research: The design of clinical trials and the publication of unsatisfactory studies, in both human and animal models, continue to cause confusion in advising on patient management. Improvements in trial design, critical assessment of studies for publication and avoidance of bias towards publication of positive results are needed. A better understanding of pathogenesis should lead to more potent interventions.

The objective of this article is to review anatomical, histological and physiological muscle changes following below-knee amputation. We searched the PubMed and Reedoc databases for studies evaluating modifications of the below-knee stump and changes over time in its anatomy, volume and histology. We also looked at postamputation modifications in gait and balance. Below-knee amputees show muscular atrophy on both the amputated side and nonamputated side, with fewer and smaller muscle fibres (particularly slow-twitch fibres). This amyotrophy varies in magnitude and distribution and can reach about 25% for the quadriceps (predominantly on the medial side), but is nonsignificant for the hamstrings. This amyotrophy results from the anatomical consequences of the surgical act. The loss of one or more of a muscle's insertions or reimplantation into a nonphysiological site prompts greater atrophy. Changes in muscle activation patterns also lead to atrophy. The hamstrings replace the tr...

Skeletal muscles adapt to changes in their workload by regulating fibre size by unknown mechanisms 1,2 . The roles of two signalling pathways implicated in muscle hypertrophy on the basis of findings in vitro 3-6 , Akt/mTOR (mammalian target of rapamycin) and calcineurin/NFAT (nuclear factor of activated T cells), were investigated in several models of skeletal muscle hypertrophy and atrophy in vivo. The Akt/mTOR pathway was upregulated during hypertrophy and downregulated during muscle atrophy. Furthermore, rapamycin, a selective blocker of mTOR 7 , blocked hypertrophy in all models tested, without causing atrophy in control muscles. In contrast, the calcineurin pathway was not activated during hypertrophy in vivo, and inhibitors of calcineurin, cyclosporin A and FK506 did not blunt hypertrophy. Finally, genetic activation of the Akt/mTOR pathway was sufficient to cause hypertrophy and prevent atrophy in vivo, whereas genetic blockade of this pathway blocked hypertrophy in vivo. We conclude that the activation of the Akt/mTOR pathway and its downstream targets, p70 S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of the Akt/mTOR pathway can oppose muscle atrophy induced by disuse.

It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to conquer these diseases which will benefit astronauts as well as people on Earth in the end; and iv) on top of that, unveiling the mechanisms of weightlessness-dependent molecular and cellular changes is a requirement for improving space medicine. In mammalian cells, microgravity induces apoptosis and alters the cytoskeleton and affects signal transduction pathways, cell differentiation, growth, proliferation, migration and adhesion.

Prolonged immobilization of the human body results in functional impairments and musculoskeletal system deconditioning that may be attenuated by adequate muscle exercise. In a 56-day horizontal bed rest campaign involving voluntary males we investigated the effects of vibration muscle exercise (RVE, 2·6 min daily) on the lower limb skeletal muscles using a newly designed foot plantar trainer (Galileo Space) for use at supine position during bed rest. The maximally voluntary isometric plantar flexion force was maintained following regular RVE bouts during bed rest (controls À18.6 %, P<0.05). At the start (BR2) and end of bed rest (BR55) muscle biopsies were taken from both mixed fast/slow-type vastus lateralis (VL) and mainly slowtype soleus muscle (SOL), each having n=10. RVE group: the size of myofiber types I and II was largely unchanged in VL, and increased in SOL. Ctrl group: the SOL depicted a disrupted pattern of myofibers I/II profiles (i.e., type II>140 % vs. preBR) suggesting a slow-to-fast muscle phenotype shift. In RVE-trained SOL, however, an overall conserved myofiber I/II pattern was documented. RVE training increased the activity-dependent expression of nitric oxide synthase type 1 immunofluorescence at SOL and VL myofiber membranes. These data provide evidence for the beneficial effects of RVE training on the deconditioned structure and function of the lower limb skeletal muscle. Daily short RVE should be employed as an effective atrophy countermeasure co-protocol preferentially addressing postural calf muscles during prolonged clinical immobilization or long-term human space missions.

We investigated the restorative potential of intensive electrical stimulation in a patient with long-standing quadriceps denervation. Stimulation started 18 months after injury. After 26 months, the thighs were visibly less wasted. Muscle cross-sectional areas, measured by computerized tomography, increased from 36.0 cm 2 to 57.9 cm 2 (right) and from 36.1 cm 2 to 52.4 cm 2 (left). Knee torque had become sufficient to maintain standing without upper extremity support. Biopsies revealed evidence of both growth and regeneration of myofibers. The results suggest that electrical stimulation may offer a route to the future development of mobility aids in patients with lower motor neuron lesions.

The purpose of this article is to present a rationale for intradialytic exercise training in patients with end-stage renal disease based on the empirical evidence to date and determine whether this evidence has translated into enhanced renal rehabilitation practices throughout the world. According to the published literature, intradialytic exercise improves exercise adoption and adherence in this cohort, is performed safely, and is feasible to administer. Moreover, intradialytic exercise can improve solute removal, dialysis adequacy, intradialytic protein synthesis, muscular strength, peak oxygen consumption, nutritional status, and quality of life. Despite these findings, there currently are no policies or position stands regarding exercise prescription for hemodialysis patients in Australia. According to a telephone survey we conducted, intradialytic exercise programs are essentially nonexistent in this country. However, such programs are being implemented successfully as standard clinical practice in dialysis units in Germany, and there is reason to believe that this practice can be expanded throughout the world. At present, additional research is indicated. There is a lack of large-scale, robustly designed, randomized, controlled trials of intradialytic exercise training. Such research is needed to conclusively show the clinical importance of intradialytic exercise for hemodialysis patients, which may influence current standard clinical practice among nephrologists and, as such, improve the health and quality of life of this vulnerable cohort. Am J Kidney Dis 45:912-916.

Neck muscle weakness and atrophy are two common causes of pain and disability among office workers. The aim of this study was to compare the strength of the neck extensor and flexor muscles and the size of the semispinalis capitis muscle (SECM) in patients with chronic non-specific neck pain (CNNP) and healthy subjects. Twenty female office workers (10 patients with CNNP and 10 healthy subjects) participated in this study. The strength of the neck extensor and flexor muscles was measured by an isometric device and the SECM size was measured by ultrasonography. Neck muscle strength, size of the SECM and the ratios of neck strength to body weight, neck extensor strength to SECM size, SECM size to body weight and neck flexor to extensor strength were all significantly lower in patients compared to controls (P < 0.05). In conclusion, neck strength, the size of the SECM and the ratio of neck muscle strength to SECM size appear to be useful parameters in appraising patients with CNNP.

Alcohol-induced muscle disease (AIMD) is a composite term to describe any muscle pathology (molecular, biochemical, structural or physiological) resulting from either acute or chronic alcohol ingestion or a combination thereof. The chronic form of AIMD is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere affecting more than 2000 subjects per 100,000 population and is thus much more common than hereditary disorders such as Becker or Duchenne muscular dystrophy. Paradoxically, most texts on skeletal myopathies or scientific meetings covering muscle disease have generally ignored chronic alcoholic myopathy. The chronic form of AIMDs affects 40–60% of alcoholics and is more common than other alcohol-induced diseases, for example, cirrhosis (15–20% of chronic alcoholics), peripheral neuropathy (15–20%), intestinal disease (30–50%) or cardiomyopathy (15–35%). In this article, we summarise the pathological features of alcoholic muscle disease, particularly biochemical changes related to protein metabolism and some of the putative underlying mechanisms. However, the intervening steps between the exposure of muscle to ethanol and the initiation of the cascade of responses leading to muscle weakness and loss of muscle bulk remain essentially unknown. We argue that alcoholic myopathy represents: (a) a model system in which both the causal agent and the target organ is known; (b) a myopathy involving free-radical mediated pathology to the whole body which may also target skeletal muscle and (c) a reversible myopathy, unlike many hereditary muscle diseases. A clearer understanding of the mechanisms responsible for alcoholic myopathy is important since some of the underlying pathways may be common to other myopathies.

Reasons for performing study: There are few detailed reports describing muscular disorders in Warmblood horses.Objectives: To determine the types of muscular disorders that occur in Warmblood horses, along with presenting clinical signs, associated risk factors and response to diet and exercise recommendations, and to compare these characteristics between horses diagnosed with polysaccharide storage myopathy (PSSM), those diagnosed with a neuromuscular disorder other than PSSM (non-PSSM) and control horses.Methods: Subject details, muscle biopsy diagnosis and clinical history were compiled for Warmblood horses identified from records of biopsy submissions to the University of Minnesota Neuromuscular Diagnostic Laboratory. A standardised questionnaire was answered by owners at least 6 months after receiving the muscle biopsy report for an affected and a control horse.Results: Polysaccharide storage myopathy (72/132 horses) was the most common myopathy identified followed by recurrent exertional rhabdomyolysis (RER) (7/132), neurogenic or myogenic atrophy (7/132), and nonspecific myopathic changes (14/132). Thirty-two biopsies were normal. Gait abnormality, ‘tying-up’, Shivers, muscle fasciculations and atrophy were common presenting clinical signs. Forty-five owners completed questionnaires. There were no differences in sex, age, breed, history or management between control, PSSM and non-PSSM horses. Owners that provided the recommended low starch fat supplemented diet and regular daily exercise reported improvement in clinical signs in 68% (19/28) of horses with a biopsy submission and 71% of horses diagnosed with PSSM (15/21).Conclusions: Muscle biopsy evaluation was a valuable tool to identify a variety of myopathies in Warmblood breeds including PSSM and RER. These myopathies often presented as gait abnormalities or overt exertional rhabdomyolysis and both a low starch fat supplemented diet and regular exercise appeared to be important in their successful management.Potential relevance: Warmbloods are affected by a variety of muscle disorders, which, following muscle biopsy diagnosis can be improved through changes in diet and exercise regimes.

The spinal muscular atrophy (SMA) gene has been Spinal muscular atrophies (SMA) are characterized mapped to chromosome 5q13 (2, 4, 6, 7), where largeby degeneration of the anterior horn cells of the spinal scale deletions have been reported (8). The SMA critical cord and represent the second most common fatal auregion contains the survival motor neuron (SMN) gene, tosomal-recessive disorder after cystic fibrosis. We which encodes a hitherto unknown protein. A highly have previously identified the survival motor neurone homologous gene is present in 95% of controls gene (SMN), a SMA-determining gene in the 5q13 re-( C BCD541). The SMN gene is either lacking or intergion encoding a hitherto unknown protein. In this rerupted in 226 of 229 SMA patients (98.7%), and paport, we describe the organization and structure of tients retaining this gene (3 of 229, 1.3%) carry either SMN. The gene is à20 kb in length and consists of nine a point mutation (Y272C) or short deletions in the conexons. Sequence data of the 5 end of the gene show sensus splice sites of introns 6 and 7 (5). Other groups that the dinucleotide repeat C272 is close to several found similar results in a large series of SMA patients putative binding sites for transcription factors, which (9, 10). Moreover, the observation of SMA patients howill help to characterize the regulation of the SMN mozygous for a frameshift SMN deletion strongly supand C BCD541 gene expression. The availability of the ports the view that SMN is the SMA-determining gene human SMN and its highly homologous counterpart ( C BCD541) gene structures and exon-intron bound-(1). In this report, we describe the organization and aries will hopefully speed up the characterization of structure of the SMN gene. (5). By virtue of restriction mapping and Southern blot 393, Hôpital des Enfants Malades, 149 rue de Sèvres 75743 Paris analysis, phages L-132, L-5, and L-13 were shown to Cedex 15, France. Telephone: 33 1 44 49 51 63. Fax: 33 1 47 34 85 14. span the entire SMN gene and were thoroughly charac-FIG. 1. Genomic structure of the human SMN gene. The designations and positions of genomic clones are shown at the top of the figure. Hatched bars indicate rearrangements of the L-132 phage. Microsatellite and DNA markers are indicated above the genomic map. The genomic sites for the enzymes EcoRI (E), HindIII (H), and BglII (B) are indicated. The positions of exons are shown below.

To evaluate the effects of electrical stimulation on denervated muscles in spinal cord injured humans, the EU Project RISE was started in 2001. The aims of this project are: to design and build sufficient stimulators; to develop stimulation protocols by means of mathematical models, animal experiments, and practice in humans with denervated lower limbs; to develop examination methods and devices for evaluation of electrical stimulation training effects; and to acquire basic scientific knowledge on denervated and stimulated denervated muscle. In the clinical study 27 spinal cord injured individuals were included, fur-

Résumé  Le patient âgé fragile est un sujet à haut risque de fracture de hanche. Toutefois, il accède peu à l’organisation aux mesures prévenant la chute et rarement à l’approche diagnostique et thérapeutique de l’ostéoporose. Cette revue de la littérature porte sur les liens entre le syndrome de fragilité et le risque de fracture de hanche. Elle fut discutée lors d’une

This review aims to provide the reader with up to date evidence in relation to the role of exercise in the reduction of risk factors and the prevention of falls and injuries. Falls and injury may lead to a spiral of inactivity and decline that take older people close to or below the critical ªthresholdsº of performance necessary for everyday activities. Yet, low strength and power, poor balance, poor gait and functional ability, and fear of falling are all risk factors for falls modifiable with tailored exercise. Although the evidence on types, amounts and specificity of exercise to prevent falls is not complete, recommendations have been published that have been effective, either as an exercise stand-alone intervention or with exercise as part of a multifactorial intervention. It is clear that the target population must be at risk or already fallers, they must be ªnot too fitº and ªnot too frailº. Supervised home-based exercise programs may be effective 77 Scand J Med Sci Sports I N S P O R T S appropriate, multidisciplinary, to allow re-referral back to the therapy setting. For those who have fallen, the physical risk factors for falls can be modified with graded, progressive, individually tailored, evidencebased and enjoyable exercise programmes, supervised by appropriately qualified exercise professionals. With the increasingly older population this must be a priority for all health providers, age-related agencies and health and fitness professionals working with older people.

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

In a clinical study of 35 dogs with avascular necrosis of the femoral head, 6 0 per cent were Yorkshire terriers; the mean age of 33 of the dogs at onset of clinical signs was seven months. The dogs had the following signs: muscle atrophy (n = 25), shortening of the affected leg (n = 14), pain on passive movement of the hip joint (n = 28), and crepitation of the hip joint (n = 8). Radiographic findings were irregular density and flattening of the femoral head in combination with degenerative joint disease. Conservative treatment consisted of exercise therapy, and surgical treatment of a standard femoral head and neck excision. In 17 of the dogs the results of therapy were evaluated with the help of a questionnaire. It is concluded that femoral head and neck excision is indicated when conservative treatment fails to lead to clinical improvement within four weeks. Femoral head and neck excision has a good long term prognosis; however, slight intermittent lameness may remain.

Periods of immobilisation are often associated with pathologies and/or ageing. These periods of muscle disuse induce muscle atrophy which could worsen the pathology or elderly frailty. If muscle mass loss has positive effects in the short term, a sustained/uncontrolled muscle mass loss is deleterious for health. Muscle mass recovery following immobilisation-induced atrophy could be critical, particularly when it is uncompleted as observed during ageing. Exercise, the best way to recover muscle mass, is not always applicable. So, other approaches such as nutritional strategies are needed to limit muscle wasting and to improve muscle mass recovery in such situations. The present review discusses mechanisms involved in muscle atrophy following disuse and during recovery and emphasises the effect of age in these mechanisms. In addition, the efficiency of nutritional strategies proposed to limit muscle mass loss during disuse and to improve protein gain during recovery (leucine supplementation, whey proteins, antioxidants and anti-inflammatory compounds, energy intake) is also discussed.

Vertebrate skeletal muscle fibers have two traits that make them unique: the fibers are multinucleated and their nuclei are post-mitotic. The activity and mass of the muscles in the body make them susceptible to constant injury. When this occurs, myonuclei can be increased or replaced by the adult stem cells of muscle, satellite cells (SCs). These SCs are vital for normal growth, repair and regeneration. This review collates recent studies to determine the size of the nuclear domains and its change with activity. The relationship between the percent change in myonuclear number, cross-sectional area, and myonuclear domain indicates that the nucleus generally maintains a highly regulated domain size in spite of large variations in fiber size. The SC divides to add nuclei for growth and repair, and the SC identification and number are discussed. It is concluded that SC number does not reflect a change in regenerative ability by the muscle. However, the SC number increases with changes ...

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

Loss of muscle mass after stroke has implications for strength and functional ability and may also contribute to impaired glucose metabolism. Therefore, prevention of muscle loss is desirable. Before interventions to prevent loss of muscle can be designed and evaluated, the expected rate, magnitude and timing of muscle loss need to be understood. A systematic search was undertaken to identify all studies that investigated changes in skeletal muscle mass, volume or crosssectional area in people after stroke. Studies that used either direct measures of muscle size (computer tomography, magnetic resonance imaging or ultrasound) or measures of lean tissue mass (dual X-ray absorptiometry) were included. Fourteen trials were found and the results were pooled for differences in lean tissue mass between the paretic and the nonparetic leg and arm as well as differences in the midthigh cross-sectional area. In individuals at least 6-month poststroke, there was significantly less lean tissue mass in the paretic compared with the nonparetic lower limb (MD 342 . 3g, 95% confidence interval 247 . 0-437 . 6 g) and upper limb (MD 239 . 9 g, 95% confidence interval 181 . 7-298 . 2 g), and significantly less midthigh muscle cross-sectional area (MD 15 . 4cm 2 , 95% confidence interval 13 . 8-16 . 9cm 2 ). There were insufficient data to pool with regard to change in muscle mass over time. There is a significant difference in the regional muscle mass in the paretic vs. the nonparetic limb in individuals greater than 6-months poststroke but little is known about how early and how quickly changes in muscle mass occur.

Motor disturbances and wasting of skeletal muscles (sarcopenia) causes significant impairment of daily life activities and is a major underlying cause for hospitalization in senescence. Herein we review data and present new findings on aging-specific changes in motoneurons, skeletal muscle and the interplay between motoneurons and target muscle fibers. Although many of the changes occurring during aging may be specific to motoneurons and myofibers, respectively, evidence indicates that myofiber regeneration in sarcopenic muscle is halted at the point where reinnervation is critical for the final differentiation into mature myofibers. Combined, evidence suggests that sarcopenia to a significant extent depend on a decreased capacity among motoneurons to innervate regenerating fibers. There are also conspicuous changes in the expression of several cytokines known to play important roles in establishing and maintaining neuromuscular connectivity during development and adulthood. We also present data showing the usefulness of rodent models in studies of successful and unsuccessful patterns of aging. Finally, we show that not only dietary restriction (DR) but also activity and social environment may modulate the pattern of aging.

Spinal muscular atrophy (SMA) is a severe autosomal recessive disease caused by a genetic defect in the survival motor neuron 1 (SMN1) gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. Depletion of the SMN protein causes muscle weakness and progressive loss of movement in SMA patients. The field of gene therapy has made major advances over the past decade, and gene delivery to the central nervous system (CNS) by in vivo or ex vivo techniques is a rapidly emerging field in neuroscience. Despite Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis being among the most common neurodegenerative diseases in humans and attractive targets for treatment development, their multifactorial origin and complicated genetics make them less amenable to gene therapy. Monogenic disorders resulting from modifications in a single gene, such as SMA, prove more favorable and have been at the fore of this evolution of potential gene therapies, and results to date have been promising at least. With the estimated number of monogenic diseases standing in the thousands, elucidating a therapeutic target for one could have major implications for many more. Recent progress has brought about the commercialization of the first gene therapies for diseases, such as pancreatitis in the form of Glybera, with the potential for other monogenic disease therapies to follow suit. While much research has been carried out, there are many limiting factors that can halt or impede translation of therapies from the bench to the clinic. This review will look at both recent advances and encountered impediments in terms of SMA and endeavor to highlight the promising results that may be applicable to various associated diseases and also discuss the potential to overcome present limitations.

This international nutrition accolade, including a $10,000 cash prize, is presented for the most outstanding ORIGINAL work directly relevant to the field of nutrition and metabolism accepted each year for publication in Nutrition: The International Journal of Applied and Basic Nutritional Sciences. All manuscripts published during 1995 were eligible and were reviewed by the Award Selection Committee. The selection was made on the basis of their recommendation.

Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1-to 37-years postspinal cord injury (SCI). After 2-to 10-years FES-training the muscle cryosections present mainly large round myofibers.

Muscle weakness is consistently associated with falls in the elderly people, typically when present along with other risk factors. However, it remains unknown whether and how muscle weakness alone affects balance. This hampers development of more effective fall prevention strategies. Clinical observations suggest that the amount and distribution of muscle weakness influences balance control. We therefore investigated balance corrections in patients with either predominantly proximal (limb girdle muscular dystrophy (LGMD); n‫)8؍‬ or distal (distal spinal muscular atrophy; n‫)5؍‬ leg weakness, and 27 matched healthy controls. Balance was perturbed using surface tilt rotations that were delivered randomly in eight directions. Balance measures were full body kinematics and surface electromyographic activity (EMG) of leg, arm, and trunk muscles. Both patient groups were more unstable than controls, as reflected by greater excursions of the centre of mass (COM), especially in the pitch (anterior-posterior (AP)) plane. COM displacements were greater in distal weakness patients. Patients with distal weakness had excessive and unstable trunk, knee and ankle movements, and this was present following both forward and backward directed balance perturbations, possibly reflecting the greater use of distal leg muscles in these directions. In contrast, the less weak proximal weakness patients demonstrated unstable trunk and ankle movements only for backward directed balance perturbations. Both patient groups used arm movements to compensate for their instability. We conclude that primarily distal but also proximal muscle weakness leads to significant postural instability. This observation, together with the retained ability of patients to use compensatory arm movements, provides targets that may be amenable to improvement with therapeutic intervention.