Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge.

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Adherence to the physical activity guideline beyond the recommended minimum weekly amount: impacts on indicators of physical function in older adults.

Introduction: The extent to which additional health benefits of accumulating twice the minimum amount of time in moderate-to-vigorous physical activity (MVPA) affects indicators of physical function in older adults is unclear. Therefore, the aim of the present study was to assess indicators of physical function in older adults who accumulate at least 150 but less than 300 min/week of MVPA compared to those accumulating at least 300 min/week. Methods: Indicators of physical function, including handgrip strength, 5 times sit-to-stand test (5-STS), squat jump and 6-min walk test (6MWT) were assessed in a sample of 193 older men (n = 71, 67 ± 2 years), and women (n = 122, 67 ± 2 years), who all accumulated at least 150 weekly minutes of MVPA. Time in MVPA was assessed by accelerometry during 1 week and engagement in muscle strengthening activities (MSA) was assessed by self-report. Protein intake was assessed by a food-frequency-questionnaire. Participants were classified as physically active (≥150 but <300 min of MVPA per week) or as highly physically active (≥300 min of MVPA per week). Results: Factorial analysis of variance revealed that older adults accumulating at least 300 min of MVPA per week had a significantly (p < 0.05) better 6MWT performance and overall physical function compared to the less active group. These findings remained significant after further adjustment for MSA, sex, waist circumference and protein intake. In contrast, no significant differences in indicators of muscle strength were observed between the two groups. Discussion: Adherence to twice the recommended minimum amount of weekly MVPA time is related to a better physical function, evidenced by a better walking performance compared to adherence to the minimum weekly amount of MVPA. This finding emphasizes the benefits of accumulating daily MVPA beyond the minimum recommended amount to optimize the ability to perform activities of daily living, thus reducing the burden of physical disability and related health-care costs.

Neither myonuclear accretion nor a myonuclear domain size ceiling is a feature of the attenuated hypertrophic potential of aged human skeletal muscle.

Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were taken at baseline and after 3-/6-week training. We determined muscle size by fibre CSA (and type), SC number, myonuclei counts and DNA synthesis (via D2O ingestion). At baseline, there were no significant differences in fibre areas between Y and O. RET increased type I fibre area in Y from baseline at both 3 weeks and 6 weeks (baseline: 4509 ± 534 µm2, 3 weeks; 5497 ± 510 µm2 P < 0.05, 6 weeks; 5402 ± 352 µm2 P < 0.05), whilst O increased from baseline at 6 weeks only (baseline 5120 ± 403 µm2, 3 weeks; 5606 ± 620 µm2, 6 weeks; 6017 ± 482 µm2 P < 0.05). However, type II fibre area increased from baseline in Y at both 3 weeks and 6 weeks (baseline: 4949 ± 459 µm2, 3 weeks; 6145 ± 484 µm2 (P < 0.01), 6 weeks; 5992 ± 491 µm2 (P < 0.01), whilst O showed no change (baseline 5210 ± 410 µm2, 3 weeks; 5356 ± 535 µm2 (P = 0.9), 6 weeks; 5857 ± 478 µm2 (P = 0.1). At baseline, there were no differences in fibre myonuclei number between Y and O. RET increased type I fibre myonuclei number from baseline in both Y and O at 3 weeks and 6 weeks with RET (younger: baseline 2.47 ± 0.16, 3 weeks; 3.19 ± 0.16 (P < 0.001), 6 weeks; 3.70 ± 0.29 (P < 0.0001); older: baseline 2.29 ± 0.09, 3 weeks; 3.01 ± 0.09 (P < 0.001), 6 weeks; 3.65 ± 0.18 (P < 0.0001)). Similarly, type II fibre myonuclei number increased from baseline in both Y and O at 3 weeks and 6 weeks (younger: baseline 2.49 ± 0.14, 3 weeks; 3.31 ± 0.21 (P < 0.001), 6 weeks; 3.86 ± 0.29 (P < 0.0001); older: baseline 2.43 ± 0.12, 3 weeks; 3.37 ± 0.12 (P < 0.001), 6 weeks; 3.81 ± 0.15 (P < 0.0001)). DNA synthesis rates %.d-1 exhibited a main effect of training but no age discrimination. Declines in myonuclei addition do not underlie impaired muscle growth capacity in older humans, supporting ribosomal and proteostasis impairments as we have previously reported.

Consumption of Vegetables Is Associated with Systemic Inflammation in Older Adults.

It is hypothesized that healthy diets rich in fruits and vegetables (FV) can modulate the inflammatory status in older adults. However, to determine the actual impact of FV on inflammatory status, adiposity level and objectively assessed physical activity (PA) behaviors need to be considered. The aim of the present study was to explore associations between FV intake and biomarkers of systemic inflammation in older adults. Based on a sample of 233 older adults (65−70 years old), the following inflammatory biomarkers were assessed: C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), IL-10, IL-18, and monocyte chemoattractant protein-1 (MCP-1). FV intake was assessed by self-report, and PA behaviors encompassing time spent sedentary and in moderate-to-vigorous PA (MVPA) were determined using accelerometers. Associations between FV intake and inflammatory biomarkers were analyzed using stepwise linear regression models while adjusting for several covariates, including health-related food groups, adherence to the MVPA guidelines, total sedentary time, and waist circumference. While no significant associations were observed for the total FV intake, the vegetable intake was inversely associated with levels of IL6 (ß = −0.15; p < 0.05). In contrast, fruit intake was not associated with any inflammatory biomarker. In conclusion, our findings indicate beneficial associations between vegetable intake and levels of a pro-inflammatory biomarker in older adults, which strengthens public health efforts to promote vegetable-rich diets in older adults to mitigate age-related systemic inflammation.

Nuts and Metabolic Syndrome: Reducing the Burden of Metabolic Syndrome in Menopause.

Menopause imposes a dramatic fall in estrogens, which is followed by an increase in the proportion of fat. The rising androgen/estrogen ratio along the menopause transition favors the accumulation of central fat, which contributes to insulin resistance and a series of concatenated effects, leading to a higher incidence of metabolic syndrome. The modulatory effect of diet on the metabolic syndrome phenotype has been shown for the Mediterranean diet, and nuts are key determinants of these health benefits. This review of the impact of nuts on the risk factors of the metabolic syndrome cluster examined studies-prioritizing meta-analyses and systemic reviews-to summarize the potential benefits of nut ingestion on the risk of metabolic syndrome associated with menopause. Nuts have a general composition profile that includes macronutrients, with a high proportion of unsaturated fat, bioactive compounds, and fiber. The mechanisms set in motion by nuts have shown different levels of efficacy against the disturbances associated with metabolic syndrome, but a beneficial impact on lipids and carbohydrate metabolism, and a potential, but minimal reduction in blood pressure and fat accumulation have been found.

Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.

BACKGROUND: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men. METHODS: Non-hypogonadal men (n = 16; 18-30 years) were randomized in a double-blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole-body RET. Participants underwent dual-energy X-ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses. RESULTS: Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF-1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF-1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET-induced phosphorylation of growth signalling proteins (e.g. AKTser473 : Z: 2.74 ± 0.6, P = 0.2 vs. P: 5.5 ± 1.1 fold change, P < 0.001, ES = 0.54 and mTORC1ser2448 : Z: 1.9 ± 0.8, P > 0.99 vs. P: 3.6 ± 1 fold change, P = 0.002, ES = 0.53). Both MPS (Z: 1.45 ± 0.11 to 1.50 ± 0.06%·day-1 , P = 0.99 vs. P: 1.5 ± 0.12 to 2.0 ± 0.15%·day-1 , P = 0.01, ES = 0.97) and (extrapolated) muscle protein breakdown (Z: 93.16 ± 7.8 vs. P: 129.1 ± 13.8 g·day-1 , P = 0.04, ES = 0.92) were reduced with hypogonadism result in lower net protein turnover (3.9 ± 1.1 vs. 1.2 ± 1.1 g·day-1 , P = 0.04, ES = 0.95). CONCLUSIONS: We conclude that endogenous T sufficiency has a central role in the up-regulation of molecular transducers of RET-induced muscle hypertrophy in humans that cannot be overcome by muscle mechano-transduction alone.

Effects of Reallocating Time Spent in Different Physical Activity Intensities on Sarcopenia Risk in Older Adults: An Isotemporal Substitution Analysis.

The role of daily time spent sedentary and in different intensities of physical activity (PA) for the maintenance of muscle health currently remains unclear. Therefore, we investigated the impact of reallocating time spent in different PA intensities on sarcopenia risk in older adults, while considering PA type (muscle strengthening activities, MSA) and protein intake. In a sample of 235 community-dwelling older adults (65-70 years), a sarcopenia risk score (SRS) was created based on muscle mass assessed by bioimpedance, together with handgrip strength and performance on the five times sit-to-stand (5-STS) test assessed by standardized procedures. Time spent in light-intensity PA (LPA), moderate-to-vigorous PA (MVPA), and being sedentary was assessed by accelerometry, and PA type (MSA) by self-report. Linear regression models based on isotemporal substitution were employed. Reallocating sedentary time to at least LPA was significantly (p < 0.05) related to a lower SRS, which remained evident after adjustment by PA type (MSA) and protein intake. Similarly, reallocating time in LPA by MVPA was related to a significantly (p < 0.05) lower SRS. Our results emphasize the importance of displacing sedentary behaviours for more active pursuits, where PA of even light intensities may alleviate age-related deteriorations of muscle health in older adults.

Benefits of Fruit and Vegetable Consumption on Prevalence of Metabolic Syndrome Are Independent of Physical Activity Behaviors in Older Adults.

Although consumption of fruits and vegetables (FV) is suggested to reduce metabolic risk, there is a paucity of studies taking advantage of objectively assessed physical activity (PA) behaviors when exploring links between FV intake and metabolic syndrome (MetS) in older adults. The aim of the present study was to determine the relationship between FV intake and MetS prevalence in a population of older community-dwelling adults, while considering time spent being sedentary and health-enhancing PA. Prevalence of MetS was determined in a population of 93 men and 152 women (age: 65-70 years). FV intake was determined by self-report and PA behaviors (time spent in moderate-to-vigorous PA (MVPA) and in sedentary) were assessed by accelerometry. Likelihood of having MetS by FV intake was determined using logistic regression with stepwise backward elimination including age, sex, educational level, total energy intake, adherence to MVPA guideline and total sedentary time as covariates. A main finding was that lower FV intakes were significantly related to higher prevalence of MetS (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.03-1.47) after considering potential influences by covariates. Additionally, we found that lower intake of vegetables but not fruits was significantly related to higher prevalence of MetS (OR: 1.47; 95%CI: 1.04-2.07). In conclusion, lower intakes of FV in general, and of vegetables in particular, significantly increased likelihood of MetS, regardless of time spent sedentary and adherence to the MVPA guideline. From a public health perspective, our findings emphasize adequate intakes of FV as an independent contributor to metabolic health status in older adults.

Associations between Circulating Inflammatory Biomarkers and Indicators of Muscle Health in Older Men and Women.

Systemic inflammation is believed to contribute to declining muscle health during aging. The present study aims to examine associations between indicators of muscle health and pro- and anti-inflammatory biomarkers in older men and women, while also considering the impacts of physical activity and protein intake. An assessment of skeletal muscle index (SMI) by bioelectrical impedance analysis, handgrip strength, and 5-sit-to-stand time, using standardized procedures, was conducted in a population of older men (n = 90) and women (n = 148) aged 65-70 years. The inflammatory biomarkers C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α were assessed in blood samples. Data were analyzed and stratified according to biological sex using multiple linear regression models. In older women, SMI was inversely associated with the pro-inflammatory markers CRP (ß = -0.372; p < 0.05), fibrinogen (ß = -0.376; p < 0.05), and IL-6 (ß = -0.369; p < 0.05). Importantly, these associations were independent of abdominal adiposity (waist circumference), protein intake, physical activity level, as well as any adherence to muscle strengthening guidelines (≥2 sessions/week). In contrast, no corresponding associations were observed in men. In conclusion, our findings indicate the detrimental influence of a pro-inflammatory environment on muscle health regardless of important lifestyle-related factors in older women. However, the lack of such associations in older men highlights the importance of considering biological sex when examining the complex interaction between the systemic inflammatory environment and muscle health.

Randomized Controlled Trial for Promotion of Healthy Eating in Older Adults by Increasing Consumption of Plant-Based Foods: Effect on Inflammatory Biomarkers.

To what extent the intake of fruit and vegetables (FV) influences inflammatory status remains elusive, particularly in older populations. The aim of the present study was to determine the effect of increased FV intake for 16 weeks on circulating biomarkers of inflammation in a population of older men and women. Sixty-six participants (65-70 years) randomly assigned to either FV or control (CON) groups were instructed to increase FV intake to five servings per day through nutritional counseling (FV) or to maintain habitual diet (CON). Dietary intake and physical activity level (PA) were determined using food frequency questionnaire and accelerometers, respectively, at the start and end of the intervention. C-reactive protein (CRP), interleukin 6 (IL-6), IL-18, macrophage inflammatory protein-1α (MIP-1α), MIP-1ß, tumor necrosis factor-α (TNF-α), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related activation-induced cytokine (TRANCE), and C-X3-C motif chemokine ligand-1 (CX3CL1, or fractalkine) were analyzed. The FV group significantly increased daily FV intake (from 2.2 ± 1.3 to 4.2 ± 1.8 servings/day), with no change in CON. Waist circumference and PA level were unchanged by the intervention. Interaction effects (time × group, p < 0.05) for TRAIL, TRANCE, and CX3CL1 denoting a significant decrease (p < 0.05) in FV but not in CON were observed. No corresponding effects on CRP, IL6, TNF-α, MIP-1α, and ß and IL-18 were observed. The present study demonstrates the influence of increased FV consumption on levels of some inflammatory biomarkers in a population of older adults. Future work is warranted to examine the clinical implications of FV-induced alterations in these inflammatory biomarkers.

Healthy Eating Is Associated with Sarcopenia Risk in Physically Active Older Adults.

Healthy Diet and physical activity may play important roles in the maintenance of muscle health during aging. The aim of the present study was to explore the impact of adherence to healthy dietary patterns on sarcopenia risk in a sample of physically active older men and women, while considering adherence to guidelines on muscle strengthening activities (MSA) and protein intake. Based on a sample of 191 physically active men and women (65-70 years), dietary intake was assessed using a 90-items food-frequency-questionnaire (FFQ) and Healthy Diet Score (HDS) was calculated. Physical activity was assessed by accelerometry and self-report. A sarcopenia risk score (SRS) was derived based on three indicators of muscle health: muscle mass was assessed using bioelectrical impedance and handgrip strength and 5 times sit-to-stand (5-STS) were determined by standardized procedures. Analysis of covariance (ANCOVA) was used to examine differences in SRS and its components across sex-specific tertiles of HDS, with adjustments for covariates including total energy intake, protein intake and MSA. A significant main effect (p < 0.05) of HDS on SRS was observed, where those belonging to the highest HDS tertile had lower SRS compared to those in the lowest tertile. A corresponding significant effect was observed for 5-STS performance, with better performance in those with the highest HDS adherence compared to those with the lowest. The present study supports guidelines emphasizing diet quality beyond amounts of macro- and micronutrients in the prevention of age-related deterioration of muscle health. Importantly, the benefits from healthy dietary patterns are evident in older adults who already adhere to guidelines for health-enhancing physical activity.

Acute effects of aerobic continuous, intermittent, and resistance exercise on glycemia in adolescents males with type 1 diabetes.

OBJECTIVE: Increased levels of physical activity is often associated with reduced HbA1c in individuals with diabetes. However, the effect on glycemic control differs between different programs of exercise. The aim of this study was to compare the acute effects on glycemia of resistance and two aerobic continuous and intermittent exercise bouts in adolescent males with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eight active males with type 1 diabetes (17.5 ± 0.8 years, BMI: 20.8 ± 2.2 kg/m2 , HbA1c: 7.2 ± 0.5% [54.9 ± 5.3 mmol/mol]) performed four experimental sessions-nonexercise (control), resistance exercise (RE) and two isocaloric continuous (CE) and intermittent (IE) cycling exercise trials-in a randomized order. Each session consisted of 45 min of exercise (except for the control modality) and 60 min of passive recovery. Venous blood was drawn for assessment of plasma glucose (PG). A two-way repeated-measures ANOVA was used for statistical comparisons. RESULTS: A significant time-to-exercise interaction effect on PG was detected. PG significantly decreased during IE (-5.1 ± 1.6 mmol/L) and CE (-5.4 ± 1.8 mmol/L) but not during RE (-1.0 ± 1.4 mmol/L, ns). Additionally, decreases in PG after IE and CE were sustained throughout the recovery period. CONCLUSIONS: While intermittent and continuous aerobic exercises are associated with a lowering of glycemia in male adolescents with type 1 diabetes, glycemia remained stable without significant alterations after resistance exercise. These findings hold important implications related to clinical exercise advice and disease management in adolescents with type 1 diabetes.

Sedentary Patterns and Systemic Inflammation: Sex-Specific Links in Older Adults.

The study aimed to examine sex-specific associations between objectively measured sedentary patterns and pro- and anti-inflammatory biomarkers in older adults when considering the moderating impact of physical activity (PA). Accelerometer-based monitoring of sedentary patterns and PA was conducted in a population of older men (n = 83; age: 67.4 ± 1.5; height: 178.7 ± 6.6 cm; weight: 80.9 ± 10.6 kg) and women (n = 146; age: 67.4 ± 1.6; height: 164.2 ± 6.1 cm; weight: 64.6 ± 10.1 kg) aged 65-70. Blood samples were collected for the assessment of the inflammatory biomarkers C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), IL-10, IL-18, and monocyte chemoattractant protein-1 (MCP-1). Data were analyzed using multiple linear regression models. Total and bouts of ≥10 min of sedentary time were inversely associated with the anti-inflammatory marker IL-10 in older men (accumulated sedentary time: ß = -0.116; bouts: ß = -0.099; all p < 0.05). Associations were independent of moderate-to-vigorous physical activity (MVPA) and total PA volume. In women, total and bouts of ≥10 min of sedentary time were detrimentally associated with the pro-inflammatory marker fibrinogen (accumulated sedentary time: ß = -0.130; bouts: ß = -0.085; all p < 0.05). Associations remained between accumulated sedentary time and fibrinogen when adjusting for MVPA and total PA volume. This study highlights sex-specific routes by which sedentary patterns impact on pro- and anti-inflammatory biomarkers in older adults. The findings support efforts to promote accumulation of time spent in PA at the expense of time in sedentary pursuits on low-grade inflammation in older men and women.

Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly.

Aging is accompanied by physiological changes affecting body composition and functionality, including accumulation of fat mass at the expense of muscle mass, with effects upon morbidity and quality of life. The gut microbiome has recently emerged as a key environmental modifier of human health that can modulate healthy aging and possibly longevity. However, its associations with adiposity in old age are still poorly understood. Here we profiled the gut microbiota in a well-characterized cohort of 201 Italian elderly subjects from the NU-AGE study, by 16S rRNA amplicon sequencing. We then tested for association with body composition from dual-energy X-ray absorptiometry (DXA), with a focus on visceral and subcutaneous adipose tissue. Dietary patterns, serum metabolome and other health-related parameters were also assessed. This study identified distinct compositional structures of the elderly gut microbiota associated with DXA parameters, diet, metabolic profiles and cardio-metabolic risk factors.

Engagement in Muscle-Strengthening Activities Lowers Sarcopenia Risk in Older Adults Already Adhering to the Aerobic Physical Activity Guidelines.

Sarcopenia in older adults is associated with a higher risk of falls, disability, loss of independence, and mortality. Current physical activity (PA) guidelines recommend engagement in muscle-strengthening activities (MSA) in addition to aerobic moderate-to-vigorous physical activity (MVPA). However, little is known about the impact of MSA in addition to adherence to the MVPA recommendation in the guidelines. The aim of the present cross-sectional study was to determine whether or not engagement in MSA is linked to sarcopenia risk in older adults who meet the PA guidelines of 150 min of MVPA per week. A total of 193 community-dwelling older men and women (65-70 years) were included in the study. A continuous sex-specific clustered sarcopenia risk score (SRS) was created based on muscle mass assessed using bioelectrical impedance analysis, handgrip strength, and five times sit-to-stand (5STS) time, assessed using standardized procedures. Adherence to PA guidelines was assessed using the Actigraph GT3x accelerometer and the EPAQ2 questionnaire. Guideline adherence to MSA twice a week was related to a significantly (p < 0.05) lower SRS compared to those who did not. This finding was evident after adjustment for adherence to the protein intake guideline and abdominal obesity. Similar impacts were observed for muscle mass and 5-STS but not for handgrip strength. In conclusion, guideline adherence to MSA is related to lower sarcopenia risk in older adults who already accumulate 150 weekly minutes of MVPA, which reinforces the promotion of the MSA guideline, alongside the MVPA guideline, to fight against sarcopenia progression in ageing populations.

Muscle mass and aerobic capacity in older women: Impact of regular exercise at middle age.

BACKGROUND: The impact of regular exercise habits at middle-age on muscle mass and function at old age remains inconclusive. While regular exercise likely represents a primary source of health-enhancing physical activity (PA), the physical demand of occupation needs to be considered. Additionally, PA level at old age should be taken into account in order to elucidate true associations between past exercise behaviors and muscle mass and function at old age. Therefore, the aim of the study was to examine the impact of regular exercise habits during middle age years on muscle mass and physical function at old age, while considering occupation and objectively assessed PA level at old age. METHODS: Self-reported leisure-time PA during middle age years [35-65 years] and present accelerometer-derived PA level were assessed in a population of community-dwelling older women (65-70 years; n = 112). Participants who accumulated at least 600 MET-min of PA per week during middle age years were classified as physically active. Skeletal muscle mass index (SMI), aerobic fitness and maximal isometric arm and leg strength were determined. Analyses of differences in muscle mass and physical function between physically active and inactive at middle age were adjusted by present PA, adiposity level, and the physical demand of former occupation (sedentary vs manual). RESULTS: Participants accumulating at least 600 MET-min of exercise-related activities during middle-age years had higher aerobic fitness (P < 0.01) and SMI (P < 0.05) at old age compared to their less active peers. Notably, these beneficial impacts were driven by exercise habits during late middle-age period [50 to 65 years], and remained significant after further adjustment by the physical demand of former occupation and present PA behavior at old age. Finally, middle-age engagement in exercise-related activities had no influence on maximal arm and leg isometric strength at old age. CONCLUSION: Our findings highlight the importance of engaging in regular PA of at least moderate intensity during middle age years in order to promote benefits at the level of muscle mass and aerobic fitness. This clearly supports the potential of PA in delaying aerobic capacity impairment and the occurrence of clinically manifest sarcopenia at old age.

The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor in vivo.

KEY POINTS: Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy. Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged. In response to VDR-knockdown mitochondrial function and related gene-set expression is impaired. In vitro VDR knockdown induces myogenic dysregulation occurring through impaired differentiation. These results highlight the autonomous role the VDR has within skeletal muscle mass regulation. ABSTRACT: Vitamin D deficiency is estimated to affect ∼40% of the world's population and has been associated with impaired muscle maintenance. Vitamin D exerts its actions through the vitamin D receptor (VDR), the expression of which was recently confirmed in skeletal muscle, and its down-regulation is linked to reduced muscle mass and functional decline. To identify potential mechanisms underlying muscle atrophy, we studied the impact of VDR knockdown (KD) on mature skeletal muscle in vivo, and myogenic regulation in vitro in C2C12 cells. Male Wistar rats underwent in vivo electrotransfer (IVE) to knock down the VDR in hind-limb tibialis anterior (TA) muscle for 10 days. Comprehensive metabolic and physiological analysis was undertaken to define the influence loss of the VDR on muscle fibre composition, protein synthesis, anabolic and catabolic signalling, mitochondrial phenotype and gene expression. Finally, in vitro lentiviral transfection was used to induce sustained VDR-KD in C2C12 cells to analyse myogenic regulation. Muscle VDR-KD elicited atrophy through a reduction in total protein content, resulting in lower myofibre area. Activation of autophagic processes was observed, with no effect upon muscle protein synthesis or anabolic signalling. Furthermore, RNA-sequencing analysis identified systematic down-regulation of multiple mitochondrial respiration-related protein and genesets. Finally, in vitro VDR-knockdown impaired myogenesis (cell cycling, differentiation and myotube formation). Together, these data indicate a fundamental regulatory role of the VDR in the regulation of myogenesis and muscle mass, whereby it acts to maintain muscle mitochondrial function and limit autophagy.

Fighting Sarcopenia in Ageing European Adults: The Importance of the Amount and Source of Dietary Proteins.

While an adequate protein intake is important for the maintenance of muscle mass during ageing, the amount and source of protein necessary for optimal prevention of sarcopenia remains to be determined. The present study aimed to investigate the influence of the amount and source of dietary proteins on sarcopenia risk in a cohort of 65-79-year-old European adults within the frame of the NU-AGE study. A total of 986 participants were included in the analysis. Skeletal muscle index (SMI), assessed by dual-energy X-ray absorptiometry (DXA), and handgrip strength (HG) were employed to create a continuous sex-specific sarcopenia risk score (SRS). Total amount together with animal- and plant-derived sources of proteins were obtained from a 7-day food record. Differences in SRS were analysed across groups of total protein intake (<0.8 g/body weight (BW); 0.8-<1.0 g/BW; 1.0-<1.2 g/BW; and ≥1.2 g/BW). The association between SRS and the different sources of protein was assessed using isocaloric substitution models adjusted by demographic, medical, and lifestyle factors. A significant linear dose-response relationship was observed, with a lower SRS linked to higher protein intakes. Based on the isocaloric substitution modelling, a reduced SRS was observed when increasing plant protein to the detriment of animal protein, while holding total protein intake constant. Further, this result remained significant after stratifying the analysis by adherence to different levels of protein intake. Our findings suggest that older adults may benefit from increasing protein intakes above current recommendations. Besides total amount, protein source should be considered when promoting health dietary habits in older adults for the prevention of sarcopenia.

Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort.

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.

Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy.

OBJECTIVE: The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofibre size and function and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo before exploring the importance of VDR expression upon muscle hypertrophy in humans. METHODS: Wistar rats underwent in vivo electrotransfer (IVE) to overexpress the VDR in the Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20 wks of resistance exercise training, with body composition and transcriptomic analysis. RESULTS: Muscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area, i.e., hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling, reflecting translational efficiency (e.g., mammalian target of rapamycin (mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodelling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were upregulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training. CONCLUSION: VDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and upregulation of ECM remodelling-related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogues.