Oxidative Stress and Nitric Oxide in Sedentary Older Adults with Intellectual and Developmental Disabilities.

Individuals with moderate-to-profound intellectual and developmental disabilities (IDD) are characterized by significant cognitive deficits, abnormal muscle tone, poor posture and balance, and inactive lifestyle. Increased oxidative stress (OS) has been implicated in a variety of chronic diseases, inflammatory conditions, aging, and even following intense physical exercise. Nitric oxide (NO) is a highly reactive mediator that has been shown to play different roles in a variety of different biological process and in aging. The aim of the study was to investigate the serum levels of global OS and NO metabolites (NOx) in sedentary and non-sedentary older adults with IDD. Global OS was measured by CR 3000 instrument, FORM system, and NOx were measured by determination of serum nitrite levels. OS and NOx levels were significantly higher in sedentary IDD comparing non-sedentary controls. The increased of OS and NOx levels suggest their possible involvement in the phenomenon of 'accelerated aging' in IDD. Our findings can provide another aspect indicating both OS and NOx as possible biochemical markers and their potential application in minimizing their negative influence through future therapeutic strategies.

Antioxidant effect of polyphenolic glabridin on LDL oxidation.

This study was conducted to determine the effect of a natural polyphenolic isoflavone antioxidant (Glabridin) on low-density lipoprotein (LDL) oxidation. Determination of the extent of LDL oxidation was done by measuring the formation of Thiobarbituric acid reactive substances (TBARS). After oral administration of licorice-root ethanol extract to healthy subjects for 6 months, the subjects' oxidative stress level as well as plasma LDL oxidation reduced by 20%. We concluded that dietary consumption of glabridin protects LDL from oxidation.

Prevalence of injuries among young adults in sport centers: relation to the type and pattern of activity.

The rate of injuries resulting from physical exercise in sport centers as well as related factors has not yet been described. The aims of this study were to describe the prevalence of self-reported activity-specific injuries, to identify the relations between injury profile and different types and patterns of physical activity and to assess whether gender is a modifying variable in that connection. Four hundred and fifty-seven men and women aged 20-35 years participated in this cross-sectional study. A questionnaire was used to evaluate the types and patterns of physical activity performed in the 12 months preceding the study and sports injuries sustained during that time. One hundred and ninety of the 457 subjects reported an injury as a result of exercising (41.6%). A relationship was found between weight training and injuries of the upper extremity (UE) for men and between spinning classes and knee injuries for women. Among those who participated in weight-training exercises, more frequent and longer duration exercise was associated with UE injury, and among those who participated in spinning classes more frequent exercise was associated with knee injury. Future injury prevention programs in sport centers should pay special attention to men who participate in weight training and to women who participate in spinning classes.

Tetracycline therapy for muscle atrophy due to immobilization.

Certain proteins such as matrix metalloproteinase -2(MMP-2) and heat shock protein 70(HSP-70) play a role during the degradation process. We hypothesized that tetracycline can be used to reduce tissue degradation in skeletal muscles exposed to immobilization. The right knee of old rats (20-months-old) was immobilized by a rigid external fixator (EF) device for 1, 2, 3 and 4 weeks. Aqueous Tetracycline solution was administrated 3 times a week, following 2 days after the EF was constructed. Control group I was immobilized for 3 weeks, did not receive tetracycline but did received saline injection, and control group II only received tetracycline for 3 weeks. MMP-2 and HSP-70 protein and mRNA levels in the gastrocnemius and soleus muscles were analyzed at the molecular level by RT-PCR and the protein level using SDS-PAGE gels and western blots. We have shown that rats treated by Tetracycline reduce the MMP-2 expression and HSP-70. Theses changes mainly occurred in type IIb and type IIa muscle fibers. Tetracycline administration has beneficial effect on expression of enzymes involved in protein degradation. This may suggest a protective effect on protein degradation during immobilization.

Expression of superoxide dismutase and matrix metalloproteinase type 2 in diaphragm muscles of young rats.

Moderate physical activity increases antioxidant defenses, whereas intensive activity is associated with oxidative stress. In this study we investigated the expression of superoxide dismutase (Cu,Zn-SOD), a major antioxidant defense enzyme, and that of the proteolytic enzyme matrix metalloproteinase-2 (MMP-2) in exercising muscle tissue. Treadmill running was used as a model to investigate the mechanism involved in muscle use and over use. Sprague-Dawley female rats (4 months old) were randomly assigned to 3 groups: running group I, trained at a slow speed (18 m/min; approximately 50% VO(2)), running group II, trained at a very fast speed (32 m/min; approximately 75% VO(2)), for 3 weeks, and group III - control, non-running group. Cu,Zn-SOD was measured spectrophotometrically at 320 nm by assessing the inhibition of cytochrome c reduction by xanthine oxidase. MMP-2 levels of protein and mRNA were assessed in the diaphragm by Western blotting and by reverse transcriptase-polymerase chain reaction, respectively. We found that Cu,Zn-SOD level significantly decreased in the crural diaphragm muscle of rats three weeks after fast speed running, whereas it remained unchanged in the sternal diaphragm muscle three weeks after slow speed running. The expression of MMP-2 increased in both fast and slow running groups; however, it was particularly prominent in the fast twitch muscle fibers type IIb. We conclude that the crural diaphragm muscle, which contains significantly more type IIb fibers, was more affected following fast speed running than the sternal/costal diaphragm muscles, which have an equal distribution of slow twitch (type I) and fast twitch (type IIb) muscle fibers.

Exercise running and tetracycline as means to enhance skeletal muscle stem cell performance after external fixation.

Prolonged limb immobilization, which is often the outcome of injury and illness, results in the atrophy of skeletal muscles. The basis of muscle atrophy needs to be better understood in order to allow development of effective countermeasures. The present study focused on determining whether skeletal muscle stem cells, satellite cells, are directly affected by long-term immobilization as well as on investigating the potential of pharmacological and physiological avenues to counterbalance atrophy-induced muscle deterioration. We used external fixation (EF), as a clinically relevant model, to gain insights into the relationships between muscle degenerative and regenerative conditions to the myogenic properties and abundance of bona fide satellite cells. Rats were treated with tetracycline (Tet) through the EF period, or exercise trained on a treadmill for 2 weeks after the cessation of the atrophic stimulus. EF induced muscle mass loss; declined expression of the muscle specific regulatory factors (MRFs) Myf5, MyoD, myogenin, and also of satellite cell numbers and myogenic differentiation aptitude. Tet enhanced the expression of MRFs, but did not prevent the decline of the satellite cell pool. After exercise running, however, muscle mass, satellite cell numbers (enumerated through the entire length of myofibers), and myogenic differentiation aptitude (determined by the lineal identity of clonal cultures of satellite cells) were re-gained to levels prior to EF. Together, our results point to Tet and exercise running as promising and relevant approaches for enhancing muscle recovery after atrophy.

Expression of matrix metalloproteinase 2 and heat shock protein-72 in immobilized muscle in rats.

Metalloproteinases (MMPs) are proteolytic enzymes that function in the extracellular matrix to degrade connective tissues. While it is clear that certain induced skeletal muscle pathologies promote increased expression of MMP-2 and heat shock protein- 72 (HSP-72), the relationship between muscle disuse and expression of MMP-2 and HSP-72 in muscles is unknown. These experiments tested the hypothesis that knee immobilization induced expression of MMP-2 and HSP-72 is disuse-dependent in a way that short-term joint immobilization increases HSP-72 expression, whereas long-term joint immobilization increases MMP-2 expression in skeletal muscles. Male rats (8 months old) completed 1, 2, 3, and 4 weeks of knee joint immobilization. Muscle mRNA and protein levels of MMP-2 and HSP-72 were assessed in Gastrocnemius (Gast), Superficial and Deep Quadriceps, and Soleus (Sol) muscles by reverse transcriptase-polymerase chain reaction and western blotting, respectively. Results reveal that during the first two weeks of immobilization there is increased protein levels of HSP-72 and expression of mRNA of HSP-72 mainly in slow twitch muscle fibers. However, 3 and 4 weeks of joint immobilization increased both mRNA and protein levels of MMP-2 in skeletal muscles containing a high percentage of fast type II fibers (i.e., Gast and superficial quadriceps). These results support the hypothesis that different periods of muscle disuse induced different proteins expression, and that the influence of joint immobilization on the expression of HSP-72 in the short-term, and MMP-2 in the long ran is associated to fiber types.

Muscle power, locomotor performance and flexibility in aging mentally-retarded adults with and without Down's syndrome.

Longer life expectancy is resulting in increasing numbers of elderly adults with mental retardation (MR). The objective of the study was to compare lower limb isokinetic muscle power, locomotor performance and flexibility of aged adult mentally-retarded individuals with and without Down's syndrome (DS). Nine subjects with MR and DS (mean age 61), and sixteen subjects with MR and without DS (mean age 63), performed leg power testing on a Biodex dynamometer. Parameters measured were dynamic torque, dynamic torque % body weight, and average power % body weight. Functional performance tests including "Timed Get-Up and Go" and flexibility were also analyzed and compared. Results indicate that in knee extension and flexion isokinetic power the MR group without DS showed significantly higher scores than the MR group with DS. The functional performance of elderly adults with MR and DS was significantly impaired compared with MR adults without DS, although no differences were observed between the two groups in the flexibility tests. It was concluded that muscle leg power, and gross motor performance of elderly mentally-retarded individuals without Down's syndrome is better than in those with Down's syndrome.

Recovery of muscles of old rats after hindlimb immobilisation by external fixation is impaired compared with those of young rats.

The right hindlimbs of 24-month-old female Wistar rats were immobilised for 4weeks using external fixation of the knee joint. In a further group, after the external fixation was removed, the rats were allowed to remobilise for an additional 4weeks. Hindlimb immobilisation for 4weeks caused a 32-42% reduction in wet weights of the hindlimb muscles of the rats as compared to those of the contralateral non-immobilised legs. After 4weeks of remobilisation the hindlimb muscles had not returned to the "control" weights. Biochemical changes in the gastrocnemius muscle resulting from the external fixation showed greatly elevated acid phosphatase activities (33.2%) and markedly reduced creatine phosphokinase activities (17.2%), which did not recover to preimmobilisation values after 4weeks of remobilisation. Light and transmission electron microscopy showed that remobilisation for 4weeks (after external fixation) resulted in only partial morphological restoration of the damage to the muscles in these aged rats. A comparison of similar hindlimb external fixation and remobilisation in young (6months old) rats showed that remobilisation caused a substantial recovery in biochemical parameters in both age groups, with the muscles of the young group (but not the old group) often reaching almost complete recovery accompanied by morphological restoration. We conclude that the net gain in the recovery period of biochemical and morphological parameters is significantly greater in the young rats compared to the old rats indicating that muscle metabolism and capacity for recovery from disuse atrophy is impaired with ageing.

Capacity for recovery and possible mechanisms in immobilization atrophy of young and old animals.

The effect of limb immobilization on muscle wasting and recovery of young and old rats was studied. Limb immobilization caused rapid and pronounced muscle weight loss, which was overcome efficiently in the muscles of young animals. However, muscles of old animals did not recover as well, indicating that muscle turnover (degradation and synthesis of proteins) is slower in old muscles than in young ones. The mechanisms of muscle wasting due to immobilization may involve two stages, the fast phase employing calcium-dependent proteolysis and the slower phase recruiting the lysosomal and ubiquitin-proteosome systems. The slow phase most probably involves the penetration of white cells between the muscle fibers and involves the secretion of cytokines that mediate a cascade of intracellular events, which culminates in muscle protein degradation. Thus, it was shown in our study and in other similar reports that through the influence of TNF-alpha and an increase in oxidative stress, there is marked activation of transcription factor NF-kappaB, which in turn induces many proteins to carry the signals that eventually result in protein breakdown. Because protein turnover was shown to slow down with age, it will be of great interest to study these events in aging muscles and to try to ascertain the specific events that make protein breakdown in aged muscles different from that in young ones.

Muscle strength and mass of lower extremities in relation to functional abilities in elderly adults.

BACKGROUND: Functional and physiological declines in advancing age may be significant limiting factors in reduced physical activity. Sarcopenia of aging, as a normative process or disease, cannot entirely explain reduced physical activity in the elderly. OBJECTIVE: The purpose of the study was to investigate the relationship between muscle loss and reduction in functional abilities in elderly adults and also to determine whether an exercise program can improve functional performance and muscle quality. METHODS: Anthropometric measurements and sensorimotor testing were conducted on 28 volunteers (12 men and 16 women, 82.7 +/- 2.4 years of age) who were permanent residents in a skilled nursing facility. Twenty-nine elderly adults (79.3 +/- 3.5 years of age) served as a control, nonexercising group. Anthropometric measurements included: weight, height, body fat, and thigh circumference. The muscle strength was tested with a medical isokinetic system. We assessed two sensorimotor functions including a 'timed up-and-go' test and a 3-min distance walking test. The institutionalized participants undertook an exercise training program lasting 12 weeks. RESULTS: No significant changes were observed in thigh circumference, body weight, or percentage of body fat in either gender as a result of the exercise training. An improvement in muscle strength was noticed in 82% of the relatively younger group (79-83 years of age) under a slow voluntary contraction at 60 degrees /s (p < 0.05). Post-training results showed a significant improvement in performance in the two sensorimotor tests (p < 0.05). The correlation coefficients between muscle strength and functional ability were weak: r = 0.60 and r = 0. 57 for males and females, respectively. CONCLUSIONS: This study confirmed the positive effects of an exercise program on functional performance in older adults. The improvement in functional abilities did not correlate with muscle strength, body weight, or body fat.

Growth hormone (GH) retardation of muscle damage due to immobilization in old rats. Possible intervention with a new long-acting recombinant GH.

Four weeks immobilization of the right leg of aged rats (26 months old) caused a marked 31% and 27% reduction of muscle mass of the plantaris and soleus muscles, respectively. In animals treated with 0.6 mg/kg body weight of growth hormone (GH), the reduction of weight of the above muscles was only 14.7 and 16.1%, respectively. Biochemical studies of the level of acid phosphatase as a marker of muscle catabolism showed a significant increase of this enzyme in the immobilized muscles. GH treatment had a positive effect in curtailing the increase due to immobilization. Studies on muscle protein oxidation used as another measure of damage in immobilized animals, showed a 400% increase in protein carbonyls in plantaris muscles. GH administration reduced this value significantly. One major issue hampering the clinical use of human GH (hGH) is its short half-life in vivo (14 min). In a previous work it was possible to enhance the in vivo longevity of other hormones such as follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) by fusing carboxyl-terminal peptide (CTP) of the hCG gene to the above hormones. The CTP has four serine-linked oligosaccharides, which have been shown to be important in maintaining the longer half-lives of these hormones. With the above rationale of using the CTP as a general target to increase the potency of bioactive hormones, we have now fused the CTP with hGH. This has provided us with a new successfully constructed recombinant hGH, which is currently being tested for its biological potency and for possible use in aging animals.

The physiology and biochemistry of skeletal muscle atrophy as a function of age.

The skeletal muscles are an important entity in the proper function of aging animals and humans. Studies have shown that until humans are 60-70 years old, age-related changes in muscle function and structure are relatively small, while after 70 years, these alterations are accelerated considerably. Factors responsible for the "aging" of skeletal muscles are complex and include intrinsic biochemical changes in muscle metabolism, changes in the distribution and size of muscle fibers, and a general loss of muscle mass. In addition, other factors like the control of muscle contraction by the motor neural system and the influence of external conditions such as exercise, immobility, nutrition and others may also contribute to the age-related decrease in muscle functions. Studies have shown that with age there is some loss of peripheral motor neurons, reduction in the number of motor units, alterations in the neuromuscular junctions, and selective denervation of Type II muscle fibers. These findings led to the concept of denervation atrophy of skeletal muscles as one of the major mechanisms for muscle degeneration in old age. However, it should be emphasized that the extent of age-related changes varies from muscle to muscle, and some do not seem to be affected by age. For example, it has been shown recently, in animal studies, that weight-bearing muscles are much more susceptible to senescent processes than non-weight-bearing muscles. More work is needed to clarify the contributions of the various factors, especially the role of muscle training in alleviating the symptoms of age-related muscle atrophy.

Effect of growth hormone on gastrocnemius muscle of aged rats after immobilization: biochemistry and morphology.

Immobilization of limbs of aged animals is associated with swift muscular damage and atrophy. We investigated the effect of rat growth hormone (rGH) on immobilized hindlimb muscles of 26-mo-old rats. Administration of rGH significantly reduced muscle weight loss and muscle protein oxidation caused by immobilization. Capillary blood volume, measured by photoplethysmography of the hindlimb, showed a 34% reduction in immobilized animals, which was eliminated by rGH. The activity of creatine phosphokinase in immobilized gastrocnemius muscle was significantly reduced by immobilization. This damage was diminished by rGH administration. Similarly, the increase in acid phosphatase activity in immobilized muscle was reduced after rGH treatment. Morphologically, marked muscle atrophy and fiber disorientation were observed in immobilized limbs. Therapy with rGH prevented some of these changes. These results indicate that administration of rGH may provide a useful means to attenuate the degenerative effects of limb immobilization of aged rats, as evident from physiological, biochemical, and morphological parameters.