Correlates of metabolic syndrome in people with chronic spinal cord injury.

PURPOSE: We aimed at identifying clinical risk factors or early markers of metabolic syndrome (MetS) in people with spinal cord injury (SCI) that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. METHODS: One hundred sixty-eight individuals with chronic (> 1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Wilcoxon rank-sum test and χ2 test were used to compare variables between groups with and without MetS. Multiple logistic regression analysis was performed to reveal independent associations with MetS among variables selected by univariate linear regression analyses. RESULTS: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple logistic regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in hours/week (OR: 0.880, 95% CI 0.770, 0.990) and more severe pain symptoms as assessed by the numeral rating scale (OR: 1.353, 95% CI 1.085, 1.793). CONCLUSION: In people with chronic SCI, intense pain symptoms and poor LTPA may indicate a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insulin-sensitivity and comorbidities.

Independent association of hypovitaminosis d with non-alcoholic fatty liver disease in people with chronic spinal cord injury: a cross-sectional study.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) and hypovitaminosis D are highly prevalent in people with spinal cord injury (SCI) and could exert an unfavorable influence on cardiovascular profile and rehabilitation outcomes. We aimed to assess the independent association between low 25-hydroxy vitamin D (25(OH)D) levels and NAFLD in people with chronic (> 1 year) SCI. METHODS: One hundred seventy-three consecutive patients with chronic SCI (132 men and 41 women) admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. RESULTS: NAFLD was found in 105 patients (60.7% of the study population). They were significantly older and exhibited a poorer leisure time physical activity (LTPA) and functional independence in activities of daily living, a greater number of comorbidities and a higher prevalence of metabolic syndrome (MetS) and its correlates, including lower HDL and higher values of body mass index (BMI), systolic blood pressure, HOMA-index of insulin resistance and triglycerides. 25(OH)D levels were significantly lower in NAFLD (median: 10.6 ng/ml, range: 2.0-31.0) than in non-NAFLD group (22.5 ng/ml, 4.2-51.6). When all these variables were included in a multiple logistic regression analysis, a significant independent association with NAFLD only persisted for lower 25(OH)D levels, a greater number of comorbidities and a poorer LTPA. The ROC analysis revealed that 25(OH)D levels < 18.25 ng/ml discriminated patients with NAFLD with a sensitivity of 89.0% and a specificity of 73.0% (AUC: 85.7%; 95%CI: 79.6-91.7%). NAFLD was exhibited by 83.9% of patients with 25(OH)D levels < 18.25 ng/ml and by 18% of those with 25(OH)D levels ≥ 18.25 ng/ml (p < 0.0001). CONCLUSION: In people with chronic SCI, 25(OH)D levels < 18.25 ng/ml may represent a marker of NAFLD independent of MetS-related features. Further studies are warranted to define the cause-effect relationships of this association.

Clinical features and prognosis of COVID-19 in people with spinal cord injury: a case-control study.

STUDY DESIGN: Observational case-control study. OBJECTIVE: Individuals with spinal cord injury (SCI) develop systemic physiological changes that could increase the risk of severe evolution of coronavirus disease 2019 (COVID-19) and result in atypical clinical features of COVID-19 with possible delay in both diagnosis and treatment. We evaluated differences in clinical features and evolution of COVID-19 between people with SCI and able-bodied individuals. SETTING: The study was conducted in an Italian inpatient rehabilitation referral center for individuals with SCI during the lockdown for the COVID-19 pandemic. METHODS: We compared clinical information between patients with SCI and able-bodied healthcare workers of the same center who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharyngeal swab polymerase chain reaction. RESULTS: Overall, 15 out of the 25 SCI patients admitted to the center and 17 out of the 69 healthcare workers tested positive for SARS-CoV-2. Patients with SCI exhibited a significantly more advanced age and a higher prevalence of comorbidities. Nevertheless, no significant differences in clinical expression of COVID-19 and treatment strategies were observed between the two groups. All hospitalized subjects were treated in nonintensive care units and no deaths occurred in either group. CONCLUSIONS: This study does not support the supposed notion that COVID-19 could exhibit atypical clinical features or a worse evolution in the frail population of people with SCI.

Testosterone, level of the lesion and age are independently associated with prostate volume in men with chronic spinal cord injury.

PURPOSE: Although men with spinal cord injury (SCI) exhibit a prostate volume significantly smaller compared to age-matched able-bodied men, the independent association of lower prostate volume with its putative determinants has never been analyzed in this population. This study was designed to identify variables independently associated with prostate volume in men with chronic SCI. METHODS: In this cross-sectional study, prostate volume of 138 men with chronic (> 1 years) SCI, aged 54.5 (25th-75th percentile: 36.0-66.0) years, was evaluated with trans-rectal ultrasonography. All patients underwent a complete neurological exam, as well as biochemical and hormonal assessment, including total testosterone (TT) levels. Free testosterone levels were calculated (cFT) by the Vermeulen formula. RESULTS: The median prostate volume was 23.4 mL. At the univariate analysis, a larger prostate volume was associated with higher TT (p = 0.00001) and cFT (p = 0.001), SCI level below T12 (p = 0.007), more advanced age (p = 0.04), lower body mass index (p = 0.04), higher functional independence score (p = 0.06), higher values of prostate-specific antigen (p = 0.12) and shorter duration of the injury (p = 0.21). However, at the multiple regression analyses, an independent and positive association only persisted between the prostate volume with either TT or cFT levels, and, to a lesser extent, with age and a level of spinal lesion below T12. A prostate volume below the median value was observed in 91.4% (32/35) of patients with both androgen deficiency (TT < 264 ng/dL) and spinal lesion level ≥ T12, but only in 16.5% (2/12) of patients with both normal androgen levels and spinal lesion level below T12 (p < 0.001). CONCLUSIONS: Our data indicate that lower testosterone levels and, to a lesser extent, a younger age and a spinal lesion level ≥ T12 represent the only variables exhibiting an independent association with a smaller prostate volume in men with SCI.

Metabolic syndrome is the key determinant of impaired vaginal lubrication in women with chronic spinal cord injury.

PURPOSE: Spinal cord injury (SCI) affects sexual health of both male and female, but little attention has been given to sexuality of SCI women. Similar to penile erection, vaginal lubrication represents a neurovascular event and then both denervation and vascular damage might contribute to its impairment. Nevertheless, the relative weight of lesion location/degree and vascular risk factors in determining hypolubrication in women with SCI has not yet been investigated. The aim of this study was to recognize among putative determinants of poor sexual arousal in women with SCI, neurogenic and vascular/metabolic independent predictors of vaginal hypolubrication. METHODS: Twenty-eight consecutive female patients admitted to a rehabilitation program because of chronic SCI (≥ 1 year) underwent clinical and biochemical evaluations, including assessment of vaginal lubrication by the Female Sexual Function Index (FSFI). As, in people with SCI, waist circumference overestimates visceral fat mass due to abdominal muscle paralysis, metabolic syndrome (MetS) was defined according to specific criteria proposed for SCI population: BMI ≥ 22 kg/m2 and two or more of the following: triglycerides ≥ 150 mg/dL (or actual treatment), HDL < 50 mg/dL, hypertension (or actual treatment), fasting glucose ≥ 100 mg/dL or diabetes mellitus type 2. RESULTS: A FSFI lubrication sub-score < 3.6, suggestive for impaired vaginal lubrication, was exhibited by 53.7% of the study population. When compared to the group with normal lubrication, a significantly higher proportion of these women had paraplegia (93.3% vs 38.5%, p = 0.003) and met the SCI-specific criteria for MetS (73.4% vs 7.6%, p = 0.0006), whereas, no significant differences were found between the two groups in the proportion of women exhibiting the single components of MetS. At the multiple logistic regression analysis, only the presence of MetS exhibited a significant independent association with impaired vaginal lubrication (OR = 3.1, 95% CI 1.2, 5.8, p = 0.01). CONCLUSIONS: In women with SCI, a clustering of modifiable vascular/metabolic risk factors, constituting the MetS, could contribute to sexual dysfunctions by affecting the vaginal lubrication, independently of the level of the spinal cord lesion.

Can the positive association of osteocalcin with testosterone be unmasked when the preeminent hypothalamic-pituitary regulation of testosterone production is impaired? The model of spinal cord injury.

PURPOSE: Osteocalcin (OCN), released from the bone matrix during the resorption phase, in its undercarboxylated form, stimulates testosterone (T) biosynthesis in mouse and a loss-of-function mutation of its receptor was associated with hypergonadotropic hypogonadism in humans. Nevertheless, when population-based studies have explored the OCN-T association, conflicting results have been reported. Hypothesizing that the evidence of a positive association between OCN and T could have been hindered by the preeminent role of a well-functioning hypothalamus-pituitary axis in promoting T biosynthesis, we explored this association in men with chronic spinal cord injury (SCI), exhibiting high prevalence of non-hypergonadotropic androgen deficiency. METHODS: Fifty-five consecutive men with chronic SCI underwent clinical/biochemical evaluations, including measurements of total T (TT), OCN and 25(OH)D levels. Free T (FT) levels were calculated by the Vermeulen formula. Comorbidity was scored by Charlson comorbidity index (CCI). RESULTS: A biochemical androgen deficiency (TT < 300 ng/dL) was observed in 15 patients (27.3%). TT was positively correlated with OCN, 25(OH)D and leisure time physical activity and negatively correlated with age, BMI and CCI. OCN was also positively correlated with calculated FT and negatively correlated with BMI and HOMA-IR. At the multiple linear regression analyses, a positive association of OCN with TT and calculated FT persisted after adjustment for confounders. CONCLUSIONS: The positive association here found between OCN and T levels in men with chronic SCI reinforces the notion that a bone-testis axis is also functioning in humans and suggests that it can be unmasked when the preeminent hypothalamic-pituitary regulation of T production is impaired.

Correlates of low testosterone in men with chronic spinal cord injury.

Although high rates of serum testosterone deficiency have been reported in men with spinal cord injury (SCI), its determinants and attributes are not yet established. The aim of this study was to recognize, among putative determinants and attributes of androgen deficiency, those significantly associated to low testosterone after adjustment for confounders recognizable in men with chronic SCI. A biochemical androgen deficiency (total testosterone <300 ng/dL) was exhibited by 18 of 51 patients (35.3%). Significant correlates of testosterone levels were as follows: weekly leisure time physical activity (LTPA) explored by the LTPA Questionnaire for people with SCI, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides and sexual symptoms, explored by the aging males' symptom (AMS) questionnaire. At the multiple linear regression analysis, among putative determinants of low testosterone, only weekly LTPA and BMI exhibited a significant association with testosterone levels, explaining 54.2 and 9.0% of testosterone variability respectively. At the linear regression models, among various putative attributes of androgen deficiency, only lower sexual desire and, at a lesser extent, higher HOMA-IR, exhibited significant associations with lower testosterone levels, after adjustment for BMI, age, comorbidities and weekly LTPA. In conclusion, poor LTPA, high BMI and low sexual desire are independent predictors of low testosterone in men with chronic SCI. This is relevant to clinical practice, as all these features are routinely assessed in rehabilitation settings for SCI. As poor LTPA and high BMI are modifiable life-style related risk factors, prospective studies could clarify whether life-style modification could increase the level of testosterone and improve the low sexual desire, relevant clinical attribute of low testosterone in men with SCI.

Involvement of mitochondrial dysfunction in the adverse effect exerted by seminal plasma from men with spinal cord injury on sperm motility.

The aetiology of severe asthenozoospermia in men with spinal cord injury includes an adverse impact of seminal plasma (SP) on sperm motility. In this study we investigated the effect exerted by SP from men with SCI on donor sperm mitochondrial activity and its reflection on motility. Donor spermatozoa were exposed (1 h) to SP from 22 ejaculates of men with SCI. Only SP from samples exhibiting both a low fructose level and an inhibitory effect on mitochondrial membrane potential (ΔΨm), assessed at flow cytometry with JC-1, affected donor sperm motility when evaluated 1 h after co-incubation. This effect was reverted by washing from SP and sperm re-suspension in medium containing glucose, in spite of persistently depressed ΔΨm. In the same samples, sperm motility and vitality dramatically decreased when evaluated 6 h after washing and re-suspension in the glucose-containing medium. Seminal plasmas which induced a disruption of ΔΨm, also enhanced a mitochondrial ROS generation, as assessed by MitoSOX red. The enhanced mitochondrial ROS generation was associated with a late induction of sperm membrane lipid peroxidation, as assessed by BODIPY C11 , when evaluated at 6 h, but not at 1 h, after washing from SP. Furthermore, activation of caspase-9 and caspase-3 accompanied the loss of ΔΨm. In conclusion, a double energetic blockage (glycolysis and mitochondrial respiration) can represent a metabolic determinant of the early adverse effect exerted by SP from men with SCI on sperm motility. Mitochondrial dysfunction-related oxidative/apoptotic mechanisms can account for later consequences on sperm motility/vitality.

Occurrence and predictors of employment after traumatic spinal cord injury: the GISEM Study.

STUDY DESIGN: Multicenter, prospective study. OBJECTIVES: To assess the occurrence and predictors of return to work after traumatic spinal cord injury (SCI). SETTING: Italian rehabilitation centers. METHODS: We evaluated patients previously included in the Italian Group for the Epidemiological Study of Spinal Cord Injuries study. A standardised telephone interview was used to collect data after a mean follow-up of 3.8 years. The main outcome measure was employment at the end of follow-up. RESULTS: A total of 403 patients, 336 men and 67 women, with a mean age of 41.8±16.3 years, were included in the follow-up. In all, 42.1% of patients were employed at the moment of the interview, though 62% reported a worsening in their employment level. Predictors of employment were education (P<0.0001), bowel continence (P=0.02), independence in mobility (P=0.0004), ability to drive (P<0.0001), participating in the community (P=0.0001) and ability to live alone (P<0.0001) while age (P<0.0001), being married (P<0.0001), tetraplegia (P=0.03), occurrence of recent medical problems (P=0.002), re-hospitalization (P=0.02), presence of architectonic barriers (P=0.009) and having a public welfare subsidy (P<0.0001), predicted unemployment. On the basis of multivariate analysis, younger age, education, absence of tetraplegia, ability to drive, ability to live alone, previous employment were independent predictors of employment after SCI. Employment at follow-up was related to several indicators of quality of life. CONCLUSION: Employment after SCI was rather frequent and was related to several patient characteristics and social factors. Specific interventions on the patient and on the social environment may favor employment after SCI and improve quality of life.

[Occupational therapy and return to work of the people with traumatic spinal cord injury (TSCI)]. / Terapia Occupazionale e reinserimento lavorativo delle persone con esiti di mielolesione (TSCI).

The aim of this study was to evaluate the employment condition of persons with TSCI 4 years after discharge from rehabilitation facilities, as well as the factors related to better outcome. In the follow-up we interviewed 403 persons. We recorded the following variables: current employment status, causes of unemployment and their correlation with demographic status, clinical status and other information. In our results 51.4% of the interviewed persons were unemployed, 34.7% had a job and 7.2% were students. Among the unemployed persons 34% had suffered an accident at work, 31% had been unable to find suitable work and 31% were retired. Employment significantly correlated with younger age, single status, being paraplegic, being autonomous in bladder/bowel management, driving a car and a better quality of life. In the multivariate analysis the factors predicting better outcome were younger age, ability to drive and a better quality of life.

Plasmatic markers of muscular stress in isokinetic exercise.

In this paper we examined the variations of plasmatic concentrations of hypoxanthine and xanthine, and their relation with other important indicators of muscular stress creatine-kinase (CK), myoglobin, uric acid, leucocytes, in prolonged, isokynetic physical exercise, performed in a concentric mode at different joint excursion. Twenty healthy male subjects performed isokinetic exercises in concentric-concentric mode, with joint excursion of 30, 60, 90 deg/sec. Blood samples were drawn at rest, immediately after exercise and after 45 min of recovery. The plasmatic concentration of hypoxanthine increased at the end of physical exercise, compared to the rest value of about 1,5 micromol/L, up to a level of greater than 19 micromol/L; the values were higher after a period of recovery of 45 min and the increase varies considerably according to the type of exercise that was performed. Myoglobin has a slight but sensible increment too, with the same trend as hypoxanthine, while CK increase without correlation to the type of exercises. The relation with other indicators of muscular activity demonstrates that in none of the different isokinetic exercises, performed at concentric mode, was there ultrastructural damage, while it is possible to come across a considerable metabolic stress, which is dissimilar in the different kinds of exercises. The results suggest that hypoxanthine can be useful in monitoring the effectiveness of a work load and the metabolic stress consequences on the muscle tissue in training or rehabilitation programs. The results also suggest that even myoglobin, at small concentrations, can have the same function.

Succinic dehydrogenase activity in human muscle mitochondria during aging: a quantitative cytochemical investigation.

A quantitative cytochemical study has been carried out on succinic dehydrogenase (SDH) activity in biopsy samples of vastus lateralis (VL) and anterior tibialis (AT) muscles from healthy men undergoing orthopaedic surgery. According to their age, the patients were divided into: young (25.0+/-4.4 years), middle-aged (50.4+/-7.5 years) and old (75.5+/-3.9 years) groups. Bioptically excised samples were processed for copper ferrocyanide preferential SDH cytochemistry. By a computer-assisted image analyser, we calculated the ratio (R): overall area of the precipitates due to the enzyme activity/area of each mitochondrion. No significant difference was found among the three age groups, despite an 8% increase of R in the adult vs. the other groups. R values are related to mitochondrial morphofunctional features since they may be modulated by enzyme activity and the physico-chemical conditions of the organelle membranes. Thus, R quantitation enables to estimate the mitochondrial capacities for adenosinetriphosphate provision. In this context, our present findings confirm previous data reporting a substantial age-related stability of muscle mitochondrial enzyme levels. In aging, energy-deficient sarcomeres are supported to be negatively selected and eliminated, while the surviving ones appear to maintain an adequate SDH activity.

Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects.

The expression of two factors involved in the nuclear-mitochondrial crosstalk, namely the mitochondrial transcription factor A (TFAM) and the nuclear respiratory factor-1 (NRF-1), was studied in human skeletal muscle biopsies of young and aged subjects. Aged subjects presented a 2.6-fold and an 11-fold increase of the levels of TFAM protein and TFAM mRNA, respectively. The increased expression of TFAM was associated to the doubling of NRF-1 DNA-binding affinity and to a 6-fold increase of NRF-1 mRNA level. The upregulation of TFAM and NRF-1, in aged skeletal muscle, appears involved in the pathway leading to the age-related increase of mitochondrial DNA content.

Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle.

To have a clearer picture of how mitochondrial damages are associated to aging, a comprehensive study of phenotypic and genotypic alterations was carried out, analyzing with histochemical and molecular biology techniques the same skeletal muscle specimens of a large number of healthy subjects from 13 to 92 years old. Histochemical data showed that ragged red fibers (RRF) appear at about 40 years of age and are mostly cytochrome c oxidase (COX)-positive, whereas they are almost all COX-negative thereafter. Molecular analyses showed that the 4977 bp deletion of mitochondrial DNA (mtDNA(4977)) and the 7436 bp deletion of mtDNA (mtDNA(7436)) are already present in individuals younger than 40 years of age, but their occurrence does not change with age. After 40 years of age the number of mtDNA deleted species, as revealed by Long Extension PCR (LX-PCR), increases, the 10422 bp deletion of mtDNA (mtDNA(10422)) appears, although with a very low frequency of occurrence, and mtDNA content is more than doubled. Furthermore, mtDNA(4977) level directly correlates with that of COX-negative fibers in the same analyzed subjects. These data clearly show that, after 40 years of age, the phenotypic and genotypic mitochondrial alterations here studied appear in human skeletal muscle and that they are closely related.

Age and sex influence on oxidative damage and functional status in human skeletal muscle.

A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex-related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities. The experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we conclude that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference maybe related to hormonal factors.

Age and sex differences in human skeletal muscle: role of reactive oxygen species.

Previous studies, conducted on experimental animals, have indicated that reactive oxygen species (ROS) are involved in the aging process. The objective of this work was to study the relationship between oxidative damage and human skeletal muscle aging, measuring the activity of the main antioxidant enzymes superoxide dismutase (total and MnSOD), glutathione peroxidase (GPx) and catalase in the skeletal muscle of men and women in the age groups: young (17-40 years), adult (41-65 years) and aged (66-91 years). We also measured glutathione and glutathione disulfide (GSH and GSSG) levels and the redox index; lipid peroxidation and protein carbonyl content. Total SOD activity was lower in the 66-91 year-old vs. the 17-40 year-old men; MnSOD activity was significantly greater in 66-91 year-old vs. 17-40 year-old women. GPx activity remained unchanged. The activity of catalase was lower in adults than in young men but higher in the aged. We observed no changes in GSH levels and significantly higher GSSG levels only in aged men vs. adult men, and a significant decrease in aged women vs. aged men. The protein carbonyl content increased significantly in the 41-65 and 66-91 year-old vs. the 17-40 year-old men. Finally, young women have lower lipid peroxidation levels than young men. Significantly higher lipid peroxidation levels were observed in aged men vs. both young and adult men, and the same trend was noticed for women. We conclude that oxidative damage may play a crucial role in the decline of functional activity in human skeletal muscle with normal aging in both sexes; and that men appear to be more subject to oxidative stress than women.

The effects of aging on enzyme activities and metabolite concentrations in skeletal muscle from sedentary male and female subjects.

Aging affects the metabolic capacity of skeletal muscle, in particular the glycolytic and respiratory capacities. The purpose of this study was to quantify biochemical alterations due to aging in muscular metabolic capacity in human skeletal muscles in sedentary subjects. The activities of various marker enzymes and metabolites related to glycolysis, Krebs' cycle and the electron transfer chain and high energy phosphate compounds were measured in muscle biopsies from the rectus abdominis, vastus lateralis, and gluteus maximus muscles of 76 sedentary subjects (32 males and 44 females) between 15 and 91 yr. No significant differences between males and females were found, but changes related to age were: a decrease in hexokinase and lactate dehydrogenase activities in the rectus abdominis; a decrease in citrate synthase activity and citrate in the vastus lateralis; an increase in pyruvate kinase activity and a decrease in ATP and creatine phosphate concentrations in the gluteus maximus. These data suggest that distinct muscles may respond differently to aging regardless of sex in sedentary subjects.

Age-dependent changes of antioxidant activities and markers of free radical damage in human skeletal muscle.

This study was conducted in order to provide evidence for the role of reactive oxygen species (ROS) in human skeletal muscle aging. We used human muscle samples obtained from hospitalized patients in an open study with matched pairs of individuals of different ages. The subjects, ranging in age from 17 to 91 years, were grouped as follows: 17-25-, 26-35-, 36-45-, 46-55-, 56-65-, 66-75-, 76-85-, and 86-91-year-old groups. To investigate the relationship between muscle aging and oxidative damage we measured total and Mn-dependent superoxide dismutase (total SOD, MnSOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities; total reduced and oxidized glutathione (GSHtot, GSH, and GSSG) levels; lipid peroxidation (LPO), and protein carbonyl content (PrC). Total SOD activity decreases significantly with age in the 66-75-year-old group, although MnSOD activity increases significantly in the 76-85-year-old group. The activity of the two H2O2 detoxifying enzymes (GSHPx and CAT) did not change with age, as do GSHtot and GSH levels. GSSG levels increased significantly (76-85- and 86-91-year-old groups) with age. We observed a significant increase in LPO levels (66-75- and 76-85-year-old groups), although the PrC content shows a trend of increase without gaining the statistical significance. These results support the idea that ROS play an important role in the human muscle aging process.