Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

Associations between muscle strength, spirometric pulmonary function and mobility in healthy older adults.

Pathological obstruction in lungs leads to severe decreases in muscle strength and mobility in patients suffering from chronic obstructive pulmonary disease. The purpose of this study was to investigate the interdependency between muscle strength, spirometric pulmonary functions and mobility outcomes in healthy older men and women, where skeletal muscle and pulmonary function decline without interference of overt disease. A total of 135 69- to 81-year-old participants were recruited into the cross-sectional study, which was performed as a part of European study MyoAge. Full, partial and no mediation models were constructed to assess the interdependency between muscle strength (handgrip strength, knee extension torque, lower extremity muscle power), spirometric pulmonary function (FVC, FEV1 and FEF50) and mobility (6-min walk and Timed Up and Go tests). The models were adjusted for age, sex, total fat mass, body height and site of enrolment. Partial mediation models, indicating both direct and pulmonary function mediated associations between muscle strength and mobility, fitted best to the data. Greater handgrip strength was significantly associated with higher FVC, FEV1 and FEF50 (p < 0.05). Greater muscle power was significantly associated with better performance in mobility tests. Results suggest that decline in mobility with aging may be caused by decreases in both muscle strength and power but also mediated through decreases in spirometric pulmonary function. Future longitudinal studies are warranted to better understand how loss of function and mass of the respiratory muscles will affect pulmonary function among older people and how these changes are linked to mobility decline.

Diagnostic criteria for sarcopenia and physical performance.

Relative and absolute muscle mass and muscle strength are used as diagnostic criteria for sarcopenia. We aimed to assess which diagnostic criteria are most associated with physical performance in 180 young (18-30 years) and 281 healthy old participants (69-81 years) of the European study MYOAGE. Diagnostic criteria included relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height squared and total lean mass), knee extension torque, and handgrip strength. Physical performance comprised walking speed, Timed Up and Go test (TUG), and in a subgroup physical fitness. Diagnostic criteria for sarcopenia and physical performance were standardized, and the associations were analyzed using linear regression models stratified by age category, with adjustments for age, gender, and country. In old participants, relative muscle mass was associated with faster walking speed, faster TUG, and higher physical fitness (all p < 0.001). Absolute muscle mass was not associated with physical performance. Knee extension torque and handgrip strength were associated with faster walking speed (both p ≤ 0.003). Knee extension torque was associated with TUG (p = 0.001). Knee extension torque and handgrip strength were not associated with physical fitness. In young participants, there were no significant associations between diagnostic criteria for sarcopenia and physical performance, except for a positive association between relative muscle mass and physical fitness (p < 0.001). Relative muscle mass, defined as lean mass or ALM percentage, was most associated with physical performance. Absolute muscle mass including ALM/height squared was not associated with physical performance. This should be accounted for when defining sarcopenia.

Diagnostic measures for sarcopenia and bone mineral density.

SUMMARY: Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia. INTRODUCTION: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome. METHODS: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height(2)), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models. RESULTS: Lean mass and ALM/height(2) were positively associated with BMD (P < 0.001). Significance remained in all sex and age subgroups after further adjustment for fat mass, except in old women. Lean mass percentage and ALM percentage were inversely associated with BMD in old women (P < 0.001). These inverse associations disappeared after adjustment for body mass. Knee extension torque and handgrip strength were positively associated with BMD in all subgroups (P < 0.01), except in old women. Walking speed and TUG were not related to BMD. CONCLUSIONS: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Combined strength and endurance training improves health-related quality of life in healthy middle-aged and older adults.

The purpose of this study was to evaluate the effects of 21 weeks of strength and/or endurance training on health related quality of life (HRQoL) in 39-77 year-old healthy subjects. 108 men and 96 women were randomized into endurance, strength, or combined training groups and controls. Strength-group performed high-intensity strength training while endurance-group performed cycle training. Combined-group completed both training protocols. Leg extension strength and maximal oxygen uptake were measured. HRQoL was assessed with a Finnish version of SF-36 questionnaire. A significant training-induced difference was observed between groups (p=0.038) in the vitality dimension of HRQoL, which was characterized by a 6.6 ± 1.5 unit increase in the combined group and no change in the other groups. Both endurance and combined training showed small improvements in certain dimensions of HRQoL. Dimensions of general (4.6 ± 1.9) and mental health (3.9 ± 1.4) improved in combined-group while general health (4.4 ± 2.0), bodily pain (5.5 ± 2.5) and role physical (6.0 ± 2.4) improved in endurance-group. Strength-group experienced increased pain ( -5.4 ± 1.8) during the experimental period. However, increased perception of pain was not observed during combined training. According to the present results both endurance and especially combined training may have potential to promote or maintain certain dimensions of HRQoL even in middle-aged and older adults.

Effects of strength, endurance and combined training on muscle strength, walking speed and dynamic balance in aging men.

The aim of this study was to examine effects of 21-week twice weekly strength (ST), endurance (ET) and combined (ST + ET 2 + 2 times a week) (SET) training on neuromuscular, endurance and walking performances as well as balance. 108 healthy men (56.3 ± 9.9 years) were divided into three training (ST; n = 30, ET; n = 26, SET; n = 31) groups and controls (C n = 21). Dynamic 1RM and explosive leg presses (1RMleg, 50%1RMleg), peak oxygen uptake using a bicycle ergometer (VO(2peak)), 10 m loaded walking time (10WALK) and dynamic balance distance (DYND) were measured. Significant increases were observed in maximal 1RMleg of 21% in ST (p < 0.001) and 22% in SET (p < 0.001) and in explosive 50%1RMleg of 7.5% in ST (p = 0.005) and 10.2% in SET (p < 0.001). VO(2peak) increased by 12.5% in ET (p = 0.001) and 9.8% in SET (p < 0.001). Significant decreases occurred in 10WALK in ST (p < 0.001) and SET (p = 0.003) and also in DYND of -10.3% in ST (p = 0.002) and -8% in SET (p = 0.028). The changes in C remained minor in all variables. In conclusion, ST and SET training produced significant improvements in maximal and explosive strength, walking speed and balance without any interference effect in SET. Significant but moderate relationships were observed between strength and dynamic balance and walking speed, while no corresponding correlations were found in the ET group.

Effects of combined endurance and strength training on muscle strength, power and hypertrophy in 40-67-year-old men.

Both strength and endurance training have several positive effects on aging muscle and physical performance of middle-aged and older adults, but their combination may compromise optimal adaptation. This study examined the possible interference of combined strength and endurance training on neuromuscular performance and skeletal muscle hypertrophy in previously untrained 40-67-year-old men. Maximal strength and muscle activation in the upper and lower extremities, maximal concentric power, aerobic capacity and muscle fiber size and distribution in the vastus lateralis muscle were measured before and after a 21-week training period. Ninety-six men [mean age 56 (SD 7) years] completed high-intensity strength training (S) twice a week, endurance training (E) twice a week, combined training (SE) four times per week or served as controls (C). SE and S led to similar gains in one repetition maximum strength of the lower extremities [22 (9)% and 21 (8)%, P<0.001], whereas E and C showed minor changes. Cross-sectional area of type II muscle fibers only increased in S [26 (22)%, P=0.002], while SE showed an inconsistent, non-significant change [8 (35)%, P=0.73]. Combined training may interfere with muscle hypertrophy in aging men, despite similar gains in maximal strength between the strength and the combined training groups.

Serum basal hormone concentrations, nutrition and physical fitness during strength and/or endurance training in 39-64-year-old women.

We examined effects of 21 weeks of strength and/or endurance training and nutrition on serum hormones and physical fitness in 39-64-year-old women. Subjects (n=79) were randomized into the endurance group (E), strength group (S), combined group (SE) and controls (C). Total body strength training and high-intensity bicycle training were used. Average energy and nutrient intake remained the same in all groups. Body fat (dual energy X-ray absorptiometry) decreased significantly in all training groups and body mass index in E, SE and C. Only SE increased total body lean mass (2.2%, p=0.001), between groups p=0.044. Maximal cycling power increased more in E (16%) and SE (17%) than in S (8%)(all p<0.001), between groups p<0.001. Knee extension strength increased only in S (7%, p=0.006) and SE (11%, p<0.001). The changes in serum hormones did not differ between the groups, except insulin-like growth factor-1 (p=0.028), characterized by an 8% (p=0.097) increase in SE and a 7% (p=0.074) decrease in C. In women combined training led to marked improvements in physical fitness and body composition. Energy and protein intake was sufficient to ensure training-induced adaptations in muscle mass and physical fitness in response to both endurance and strength training, even though the energy balance was slightly negative in the endurance-trained groups.

Strength, [corrected] endurance or combined training elicit diverse skeletal muscle myosin heavy chain isoform proportion but unaltered androgen receptor concentration in older men.

We investigated whether the myosin heavy chain (MyHC) proportion and androgen receptor (AR) concentration in skeletal muscle differ following 21 weeks of strength, endurance and combined training in untrained older men. Strength (S) and endurance (E) groups trained twice per week and combined (S+E) group trained four times per week (two strength and two endurance). Muscle biopsies were obtained before and after the training period from m. vastus lateralis (VL) and AR mRNA and protein concentration and MyHC proportion were determined. 1RM increased during the training period in S, S+E and E but the changes were greater in S and S+E than in E. Statistically significant increases were observed only in S and S+E in maximal isometric force as well as in VL thickness. VO (2max) increased significantly only in E. MyHCIIa proportion increased in S, while MyHCIIa proportion decreased and MyHCI increased (p<0.05) in E. No statistically significant changes were observed in serum testosterone and in AR mRNA or protein concentrations. The present results indicate that 21 weeks of strength, endurance or combined training changed MyHC proportion according to the training method but did not have an effect on AR mRNA or protein expression in skeletal muscle at rest.

Effects of strength and endurance training on metabolic risk factors in healthy 40-65-year-old men.

This study compared 21 weeks of combined high-intensity strength and endurance training with endurance or strength training only on metabolic risk factors in 40-65-year-old men. The healthy men (n=63) were randomized into endurance (E), strength (S), combined strength and endurance training (SE) and control (C) groups. S and E trained two times a week and SE 2+2 times a week. Systolic (SBP) and diastolic blood pressure decreased significantly both in E (-6+/-8 and -4+/-6 mmHg) and in S (-9+/-8 and -5+/-7 mmHg), but not in SE or C (P=0.003 for the difference in the changes of SBP between the groups). The changes in serum glucose and insulin during an oral glucose tolerance test did not differ between the groups. Only E decreased serum fasting insulin levels (-17+/-27%, P=0.013). Minor changes were observed in blood lipids and lipoproteins in all groups. Both endurance and strength training can modestly improve metabolic health even in relatively lean older men with normal glucose tolerance. Combined strength and endurance training did not produce complementary benefits on metabolic risk factors. Combined training is effective in improving body composition and cardiorespiratory and muscular fitness, however, which is likely to decrease the risk of future metabolic and cardiovascular disease.

Effects of strength and endurance training on antioxidant enzyme gene expression and activity in middle-aged men.

This study was aimed at investigating the effects of a 21-week period of progressive strength or endurance training on peripheral blood mononuclear cells (PBMC) antioxidant enzyme gene expression and activity in healthy middle-aged untrained men. Strength (n=11) and endurance (n=12) training were performed twice a week, including resistance exercises to activate all the main muscle groups or cycle-ergometer pedaling, respectively. mRNA levels of catalase, glutathione peroxidase (GPx), mitochondrial superoxide dismutase (MnSOD) and cytosolic superoxide dismutase (CuZnSOD) were increased after 21 weeks of strength training, while endurance training induced significant changes only in MnSOD and GPx mRNA levels. CuZnSOD protein content was significantly increased only in strength-trained subjects. The program of strength or endurance exercise training had no significant effects on the activity of any of the antioxidant enzymes. In conclusion, in a middle-aged population, 21 weeks of strength or endurance training was a sufficient stimulus to up-regulate mRNA levels of PBMC antioxidant enzymes, the strength training being a more optimal stimulus. However, the discrepancies between enzyme protein and mRNA levels suggest that the present systematic strength or endurance training period had no beneficial effects on enzymatic antioxidant defense mechanisms in previously untrained middle-aged men.