Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians.

Background: Master athletes (MAs) prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear. Methods: We performed muscle biopsies in 15 octogenarian world-class track and field MAs and 14 non-athlete age/sex-matched controls (NA) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mitochondrial DNA (mtDNA) copy number, and proteomics by liquid-chromatography mass spectrometry. Results: MA exhibited markedly better performance on clinical function tests and greater cross-sectional area of the vastus lateralis muscle. Proteomics analysis revealed marked differences, where most of the ~800 differentially represented proteins in MA versus NA pertained to mitochondria structure/function such as electron transport capacity (ETC), cristae formation, mitochondrial biogenesis, and mtDNA-encoded proteins. In contrast, proteins from the spliceosome complex and nuclear pore were downregulated in MA. Consistent with proteomics data, MA had fewer respiratory compromised fibers, higher mtDNA copy number, and an increased protein ratio of the cristae-bound ETC subunits relative to the outer mitochondrial membrane protein voltage-dependent anion channel. There was a substantial overlap of proteins overrepresented in MA versus NA with proteins that decline with aging and that are higher in physically active than sedentary individuals. However, we also found 176 proteins related to mitochondria that are uniquely differentially expressed in MA. Conclusions: We conclude that high function in advanced age is associated with preserving mitochondrial structure/function proteins, with underrepresentation of proteins involved in the spliceosome and nuclear pore complex. Whereas many of these differences in MA appear related to their physical activity habits, others may reflect unique biological (e.g., gene, environment) mechanisms that preserve muscle integrity and function with aging. Funding: Funding for this study was provided by operating grants from the Canadian Institutes of Health Research (MOP 84408 to TT and MOP 125986 to RTH). This work was supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, USA.

Denervation drives mitochondrial dysfunction in skeletal muscle of octogenarians.

KEY POINTS: Mitochondria are frequently implicated in the ageing of skeletal muscle, although the role of denervation in modulating mitochondrial function in ageing muscle is unknown. We show that increased sensitivity to apoptosis initiation occurs prior to evidence of persistent denervation and is thus a primary mitochondrial defect in ageing muscle worthy of therapeutic targeting. However, at more advanced age, mitochondrial function changes are markedly impacted by persistent sporadic myofibre denervation, suggesting the mitochondrion may be a less viable therapeutic target. ABSTRACT: Experimental denervation modulates mitochondrial function, where changes in both reactive oxygen species (ROS) and sensitivity to permeability transition are implicated in the resultant muscle atrophy. Notably, although denervation occurs sporadically in ageing muscle, its impact on ageing muscle mitochondria is unknown. Because this information has important therapeutic implications concerning targeting the mitochondrion in ageing muscle, we examined mitochondrial function in skeletal muscle from four groups of humans, comprising two active (mean ± SD age: 23.7 ± 2.7 years and 71.2 ± 4.9 years) and two inactive groups (64.8 ± 3.1 years and 82.5 ± 4.8 years), and compared this with a murine model of sporadic denervation. We tested the hypothesis that, although some alterations of mitochondrial function in aged muscle are attributable to a primary organelle defect, mitochondrial dysfunction would be impacted by persistent denervation in advanced age. Both ageing in humans and sporadic denervation in mice increased mitochondrial sensitivity to permeability transition (humans, P = 0.004; mice, P = 0.01). To determine the contribution of sporadic denervation to mitochondrial function, we pharmacologically inhibited the denervation-induced ROS response. This reduced ROS emission by 60% (P = 0.02) in sporadically denervated mouse muscle, which is similar to that seen in humans older than 75 years (-66%, P = 0.02) but not those younger than 75 years. We conclude that an increased sensitivity to permeability transition is a primary mitochondrial defect in ageing muscle. However, at more advanced age, when muscle atrophy becomes more clinically severe, mitochondrial function changes are markedly impacted by persistent sporadic denervation, making the mitochondrion a less viable therapeutic target.

Reduction in single muscle fiber rate of force development with aging is not attenuated in world class older masters athletes.

Normal adult aging is associated with impaired muscle contractile function; however, to what extent cross-bridge kinetics are altered in aging muscle is not clear. We used a slacken restretch maneuver on single muscle fiber segments biopsied from the vastus lateralis of young adults (∼23 yr), older nonathlete (NA) adults (∼80 yr), and age-matched world class masters athletes (MA; ∼80 yr) to assess the rate of force redevelopment (ktr) and cross-bridge kinetics. A post hoc analysis was performed, and only the mechanical properties of "slow type" fibers based on unloaded shortening velocity (Vo) measurements are reported. The MA and NA were ∼54 and 43% weaker, respectively, for specific force compared with young. Similarly, when force was normalized to cross-sectional area determined via the fiber shape angularity data, both old groups did not differ, and the MA and NA were ∼43 and 48% weaker, respectively, compared with young (P < 0.05). Vo for both MA and NA old groups was 62 and 46% slower, respectively, compared with young. Both MA and NA adults had approximately two times slower values for ktr compared with young. The slower Vo in both old groups relative to young, coupled with a similarly reduced ktr, suggests impaired cross-bridge kinetics are responsible for impaired single fiber contractile properties with aging. These results challenge the widely accepted resilience of slow type fibers to cellular aging.

Effect of Elliptical High Intensity Interval Training on Metabolic Risk Factor in Pre- and Type 2 Diabetes Patients: A Pilot Study.

OBJECTIVE: The purpose of the current study was to examine the impact of 12 weeks of elliptical high intensity interval training (HIIT) on metabolic risk factors and body composition in pre- and type 2 diabetes patients. METHODS: Sixteen pre- (n = 8) and type 2 diabetes (n = 8) participants completed this study. Fasting blood glucose, HbA1c, anthropometric measurements, body composition (DXA), blood pressure, resting heart rate, VO2max, and dietary factors, as well as total and physical activity energy expenditure, were measured. The HIIT program on the elliptical was performed 3 times a week for 12 weeks. RESULTS: After the intervention, we observed a significant improvement for fasting blood glucose, waist and hip circumference, appendicular fat mass, leg lean body mass and appendicular lean body mass, systolic blood pressure, resting heart rate, and VO2max (P < .05). In addition, we noted a lower tendency for leg fat mass (P = .06) and diastolic blood pressure (P = .05) as well as a higher tendency for total energy expenditure (P = .06) after the intervention. CONCLUSION: The current study indicates that elliptical HIIT seems to improve metabolic risk factors and body composition in pre- and type 2 diabetes patients.

Relationship between long sleep duration and functional capacities in postmenopausal women.

STUDY OBJECTIVE: The purpose of the present study was to examine the relationship between long sleep duration and functional capacities. METHODS: We conducted a cross-sectional study at the Department of Kinanthropology at the University of Quebec at Montreal. Forty eight non-frail postmenopausal women aged between 49 to 75 years were recruited using advertisements in local papers. Body weight, body mass index, fat mass, skeletal muscle mass, number of steps per day, SF-36 total (healthy questionnaire), resting metabolic rate, total energy intake, sleep duration, knee extensor strength (dynamometer), chair stand test and balance opened eyes test were measured. RESULTS: WE FOUND A SIGNIFICANT NEGATIVE CORRELATION BETWEEN HOURS OF SLEEP AND FUNCTIONAL CAPACITY: chair stand test (r = -0.33, p = 0.02), balance opened eyes test (r = -0.45, p = 0.001), muscle strength (r = -0.43, p = 0.002) and skeletal muscle mass (r = -0.39, p = 0.007). In addition, long sleepers (> 9 h) had significantly lower values for skeletal muscle mass (p = 0.03), muscle strength (p = 0.01), chair stand test (p = 0.03), and balance opened eyes test (p = 0.001). Finally, linear regression analysis showed that sleep duration was an independent predictor of the chair stand test (p = 0.024), balance opened eyes test (p = 0.001), and muscle strength (p = 0.035) in our cohort. CONCLUSION: Long sleepers were associated with lower functional capacities in our cohort of sedentary postmenopausal women.

Muscle quality as a potential explanation of the metabolically healthy but obese and sarcopenic obese paradoxes.

BACKGROUND: Obesity has been associated with metabolic complications. However, two subgroups of obese individuals (namely "sarcopenic obese" and "metabolically healthy but obese" individuals) with low muscle mass appear to have a better metabolic profile. Despite having a lower muscle mass, these individuals appear to have higher muscle strength, suggesting higher muscle quality. Studies have reported insulin sensitivity to be related to muscle quality. Therefore, the aim of the present study was to test the hypothesis that low muscle mass was associated with better muscle quality in obese individuals. METHODS: A total of 112 postmenopausal women aged between 50 and 77 years (means, 61±6 years) were recruited. Body composition (bioelectrical impedancemetry), muscle strength (hand dynamometer), and functional capacity (chair stand test, alternate step test and balance test) were measured. RESULTS: Skeletal muscle mass (SM; kg) was significantly positively correlated with muscle strength (kg) in normal weight (r=0.43; P=0.003) and overweight (r=0.42; P=0.020) women, but not in obese (r=0.28; P=0.13) women. Muscle mass (kg) was significantly negatively correlated with muscle quality (kg/SMkg) in normal weight (r=-0.41, P=0.005), overweight (r=-0.59; P<0.001) and obese (r=-0.59; P<0.001) individuals. Skeletal muscle mass index (kg/m(2)) was significantly negatively correlated with muscle quality in normal weight (r=-0.33, P=0.025), overweight (r=-0.47, P=0.008), and obese (r=-0.43, P=0.015) women. Finally, type II sarcopenic individuals had higher muscle quality than type I sarcopenic (P=0.002) and nonsarcopenic (P=0.001) individuals. CONCLUSIONS: Our results support our hypothesis and showed that muscle quality increased as muscle mass and muscle mass index decreased. Thus, muscle quality may potentially explain the favorable metabolic profile observed in metabolically healthy but obese and sarcopenic obese postmenopausal women. Further studies including metabolic data are needed to confirm our results.

Effects of tai chi training in dynapenic and nondynapenic postmenopausal women.

OBJECTIVE: The purpose of the present study was to investigate the effects of a 12-week tai chi program in type I dynapenic and nondynapenic postmenopausal women. METHODS: Sixty-two postmenopausal women were recruited. Body composition, handgrip strength, functional capacities, cardiorespiratory functions (forced expiratory volume in 1 s and oxygen consumption per unit time peak), and quality of life (36-item Short-Form Health Survey) were measured before and after the intervention. RESULTS: Type I dynapenic postmenopausal women showed a significant decrease in body weight (P = 0.004), fat mass percentage (P = 0.02), and skeletal muscle mass (SM; in kilograms; P = 0.02), whereas handgrip strength (in kilograms per SMkg; P = 0.04), functional capacity test scores (P ≤ 0.050), and general health perception (P = 0.01) significantly increased. In nondynapenic postmenopausal women, we observed a significantly decreased waist circumference (P = 0.04) and a significantly increased chair-stand test (P < 0.001) and one-leg stance test (P = 0.04) scores. In addition, significantly lower systolic (P ≤ 0.001) and diastolic (P ≤ 0.005) blood pressures were observed in both groups after the intervention. Finally, type I dynapenic women showed a more pronounced general health perception increase compared with nondynapenic individuals (P = 0.03). CONCLUSIONS: Tai chi training improved body composition, muscle strength, functional capacities, and general health perception in postmenopausal women, and this last improvement was more pronounced in type I dynapenic individuals. Therefore, tai chi may be considered as an alternative physical training method in preventing the occurrence of disabilities and frailty in postmenopausal women with type I dynapenia.

Relationship between essential amino acids and muscle mass, independent of habitual diets, in pre- and post-menopausal US women.

The purpose of this secondary analysis was to examine the relationship between protein and essential amino acids (EAAs) intake with the level of muscle mass (MM) independent of the diet. Twenty-one omnivores, 22 ovo-lacto-vegetarians and 20 vegans were recruited. MM (urinary creatinine), dietary intake (5-day dietary records) and biochemical analyses (urinary and plasma sex hormones) were obtained. We observed no significant difference between groups for MM, total EAA intake, leucine, isoleucine, age and body mass index. However, we observed a significant difference between groups for total dietary protein intake and total energy intake. Despite significant differences in total dietary protein, the EAA intake was not different, indicating that neither the amount nor the quality of protein in these diets was a limiting factor in determining the amount of MM. Thus, each of these diet patterns appears adequate to maintain MM.

Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women.

The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.