Loss of Hypoxia Signaling Limits Physiologic and Muscle Adaptations to Aerobic Exercise in Aging

To assess the differential effects of exercise with age, Young (Y, 10-12 weeks) and Old (O, 23-25 months) mice were subjected to regimented treadmill running or no regimented exercise. Y, trained mice experienced a significant increase in maximal distance running, maximal speed of running, and lean muscle mass in comparison to age-matched, untrained controls. O mice did not improve significantly in any of these measures following training. Transcriptome analysis of gastrocnemius from Y mice demonstrated differential regulation of 120 genes with exercise. None of these genes were similarly regulated in the O group. Genes most upregulated following exercise in Y mice were direct targets of the hypoxia signaling pathway. Immunoblotting demonstrated that aryl hydrocarbon receptor nuclear translocator (ARNT), a critical regulator of hypoxia signaling, increased 3-fold with exercise in Y mice, but this increase was absent in O mice following exercise. To assess whether this loss of ARNT in O muscle impaired the exercise response, we generated a mouse with inducible, skeletal muscle-specific knockout of ARNT (ARNT muscle (m) KO). Following regimented exercise, ARNT mKO mice did not improve maximal distance running, maximal running speed, or lean muscle mass in comparison to untrained ARNT mKO mice. Littermate, age-matched ARNT wild type mice increased significantly in all of these measures following training. Administration of ML228, an ARNT agonist, increased maximal running distance and speed in response to exercise training in O mice. These results suggest that restoration of ARNT and hypoxia signaling may restore the physiologic response to exercise in aging.

Chronic Nutrition Impact Symptoms Are Associated with Decreased Functional Status, Quality of Life, and Diet Quality in a Pilot Study of Long-Term Post-Radiation Head and Neck Cancer Survivors

Background: As a result of tumor location and treatment that is aggressive, head and neck cancer (HNC) survivors experience an array of symptoms impacting the ability and desire to eat termed nutrition impact symptoms (NISs). Despite increasing cancer survival time, the majority of research studies examining the impact of NISs have been based on clinical samples of HNC patients during the acute phase of treatment. NISs are often chronic and persist beyond the completion of treatment or may develop as late side effects. Therefore, our research team examined chronic NIS complications on HNC survivors’ functional status, quality of life, and diet quality. Methods: This was a cross-sectional study of 42 HNC survivors who were at least 6 months post-radiation. Self-reported data on demographics, NISs, quality of life, and usual diet over the past year were obtained. Objective measures of functional status included the short physical performance battery and InBody© 270 body composition testing. NISs were coded so a lower score indicated lower symptom burden, (range 4–17) and dichotomized as ≤10 vs. >10, the median in the dataset. Wilcoxon rank sum tests were performed between the dichotomized NIS summary score and continuous quality of life and functional status outcomes. Diet quality for HNC survivors was calculated using the Healthy Eating Index 2015 (HEI-2015). Wilcoxon rank sum tests examined the difference between the HNC HEI-2015 as compared to the National Health and Nutrition Examination Survey (NHANES) data calculated using the population ratio method. Results: A lower NIS score was statistically associated with higher posttreatment lean muscle mass (p = 0.002). A lower NIS score was associated with higher functional (p = 0.0006), physical (p = 0.0007), emotional (p = 0.007), and total (p < 0.0001) quality of life. Compared to NHANES controls, HNC survivors reported a significantly lower HEI-2015 diet quality score (p = 0.0001). Conclusions: Lower NIS burden was associated with higher lean muscle mass and functional, physical, emotional, and total quality of life in post-radiation HNC survivors. HNC survivors reported a significantly lower total HEI-2015 as compared to healthy NHANES controls, providing support for the hypothesis that chronic NIS burden impacts the desire and ability to eat. The effects of this pilot study were strong enough to be detected by straight forward statistical approaches and warrant a larger longitudinal study. For survivors most impacted by NIS burden, multidisciplinary post-radiation exercise and nutrition-based interventions to manage NISs and improve functional status, quality of life, and diet quality in this survivor population are needed.

Body composition and bone mineral density in postmenopausal women with rheumatoid arthritis

Aim – to study the relationship between body composition and bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA).Material and methods. 68 postmenopausal women, median age 59 [54; 63] years, with RA were included in the study. Bone mineral density (BMD) and body composition were assessed with dual energy X-ray absorptiometry.Results. 33 (48.5%) women had osteopenia, and 17 (25.0%) – osteoporosis (OP). Low lean muscle mass was found in 10 (14.7%) patients. There were positive correlations between different areal BMD and body weight, trunk fat, trunk lean muscle mass and total lean muscle mass. In the multivariate linear regression analysis total lean muscle mass was associated with BMD of lumbar spine (β=0.638; p=0.001) and total hip (β=0.473; p=0.008), and appendicular lean muscle mass, estimated using the appendicular muscle index, with femoral neck BMD (β=0.360; p=0.014).Conclusion. 73.5% of patients with RA had a reduced BMD, and 14.7% women – low muscle mass. The revealed significant association between the lean muscle mass and BMD of lumbar spine and proximal femur indicates the importance of detecting and correcting low lean muscle mass, as well as preventing its decline in order to prevent loss of BMD and osteoporotic fractures.

AB0795 DYNAMIC CHANGES IN QUANTITATIVE INDICES OF BODY COMPOSITION BY DUAL-ENERGY X-RAY ABSORPTIOMETRY IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS ON DIFFERENT THERAPEUTIC REGIMENS

Background:A redistribution of body fat (abdominal obesity) is quite common in RA patients. Such parameters as body mass index (BMI) and waist circumference do not distinguish or quantify fat and lean (muscle) mass. For that purpose, dual-energy X-ray absorptiometry (DXA) is usually used.Objectives:to compare quantitative body composition in patients with early RA at baseline and after 24 weeks of therapy with different regimens.Methods:The study included 37pts (31 women /6 men) with early RA (ACR/EULAR criteria, 2010), 57 [46.5, 62,0] years old, naïve to treatment with glucocorticoids and disease-modifying anti-rheumatics (DMARDs). Pts were seropositive for IgM RF (76%) and anti-CCP (92%), with highly active RA (DAS28 5,5 [5,1; 6,0]; SDAI 32,4 [22,4; 42], CDAI 29,0 [19,7; 39,5]) scores, and median disease duration of 6.0 [5,5;15.5] months. Methotrexate (MTX) 10 [10-15] mg/week subcutaneously was initiated in all included patients as first line therapy for 12 weeks. By this time point therapy was reviewed in 19 patients (51%) due to MTX inefficacy and adalimumab (ADA) at 40 mg once every 2 weeks was added on top of MTX. DXA scan (HOLOGIC, USA) was used to measure body composition at baseline and after 6mths of treatment with the protocol assessing total body, body fat and lean muscle mass.Results:Based on therapeutic regimens at week 24 all study subjects were divided into 2 groups: Group I (n=18) receiving MTX monotherapy, Group II (n=19) – the combination of MTX and ADA (Table 1). Group I patients had lower body weight, lean and fat mass vs patients from Group II (62 kg vs. 73.7 kg; 40.6 kg vs. 49.7 kg; 21.0 kg vs. 25.8 kg, respectively (p<0.05 in all cases) at baseline. 24 weeks of combination therapy eventuated in body weight gain (73.7 kg vs. 75.8 kg), accumulation of fat (25.8 kg vs. 28.1 kg) and unchanged lean tissue mass. In contrast, patients on MTX monotherapy managed to increase their lean mass (40.6 kg vs. 41.6 kg) without gaining in total fat mass.Table 1.IndicesI group (n=18),monotherapy МТII group (n=19),combination therapy (MTX, ADA)baseline24 weeksΔ,%baseline24 weeksΔ,%Body fat mass, kg21,0 [17,2;26,2]**23,4 [17,5;29,7]+1125,8 [18,4;35,0]28,1 [21,4;37,9]*+9Lean mass, kg40,6 [37,3;44,7]**41,6 [38,2;46,4]***/*+2,549,7 [39,0;56,1]49,9 [41,0;57,6]0,4Total mass, kg62,0 [57,7;77,6]**64,1 [59,5;81,6]***+3,473,7 [64,5;97,9]75,8 [66,8;102,1]*+2,8*p<0,05 reliability of differences in parameters before treatment and after 6mth (Wilcoxon); **p<0.05 differences in baseline values in groups I and II (Mann-Whitney test);***p<0.05 difference in the indices between the groups by the 6mth of therapy; Δ,% difference in indices between the groups by the 6mth of therapy.Conclusion:In general, RA patients on treatment tend to gain weight by week 24. Patients who failed on MTX monotherapy by week 24 and were switched to combination therapy had higher fat mass at baseline. Mediations used for RA treatment produce multidirectional effects on quantitative parameters of body composition: MTX monotherapy triggers some increase of lean mass, while combination of MTX and bDMARD results in weight gain and increase of total and fat mass. These data need to be confirmed in large-scale studies with longer follow-up period.Disclosure of Interests:None declared

Musculoskeletal profile of amateur combat athletes: body composition, muscular strength and striking power

Background: Previous research highlighted positive musculoskeletal adaptations resulting from mechanical forces and loadings distinctive to impacts and movements with sports participation. However, little is known about these adaptations in combat athletes. The aim of this study was to quantify bone mineral density, lean muscle mass and punching and kicking power in amateur male combat athletes. Methods: Thirteen male combat athletes (lightweight and middleweight) volunteered all physiological tests including dual energy X-ray absorptiometry for bone mineral density (BMD) segmental body composition (lean muscle mass, LMM), muscle strength and striking power, sedentary controls (n = 15) were used for selected DXA outcome variables. Results: There were significant differences (p < 0.05) between combat groups for lumbar spine (+5.0%), dominant arm (+4.4%) BMD, and dominant and non-dominant leg LMM (+21.8% and +22.6%). Controls had significantly (p < 0.05) high adiposity (+36.8% relative), visceral adipose tissue (VAT) mass (+69.7%), VAT area (+69.5%), lower total body BMD (−8.4%) and lumbar spine BMD (−13.8%) than controls. No differences in lower limb BMD were seen in combat groups. Arm lean mass differences (dominant versus non-dominant) were significantly different between combat groups (p < 0.05, 4.2% versus 7.3%). There were no differences in punch/kick power (absolute or relative) between combat groups. 5RM strength (bench and squat) correlated significantly with upper limb striking power (r = 0.57), dominant and non-dominant leg BMD (r = 0.67, r = 0.70, respectively) and total body BMD (r = 0.59). Conclusion: BMD and LMM appear to be particularly important to discriminate between dominant and non-dominant upper limbs and less so for lower limb dominance in recreational combat athletes.

Relationship Between Body Segment Mass and Running Performance in Well-Trained Endurance Runners

This study examined the relationship between body segment mass and running performance in endurance runners. The total (muscle, fat, and bone masses), lean (muscle mass), and fat masses of the leg, arm, and trunk segments in 37 well-trained endurance runners were measured using dual-energy X-ray absorptiometer. The relative segment mass was calculated by normalizing the absolute mass to body mass. There were no significant correlations between absolute total, lean, and fat masses of all 3 segments and personal best 5000-m race time. No significant correlations were also observed between all 3 relative masses of the arm segment and personal best 5000-m race time. In contrast, medium positive correlations were observed between the relative total and lean masses of the leg segment and personal best 5000-m race time (r = .387 and .335, respectively, both P ≤ .031). Furthermore, large negative correlations were observed between the relative total and lean masses of the trunk segment and personal best 5000-m race time (r = −.500 and −.548, respectively, both P ≤ .002). These findings suggest that a mass distribution with smaller leg mass and greater trunk mass may be advantageous for achieving better running performance in endurance runners.

Intranasal Oxytocin Improves Lean Muscle Mass in Older Adults With Sarcopenic Obesity: A Pilot Study

Obese older adults often have sarcopenia with increased functional impairments. Unfortunately, conventional weight loss treatments can lead to further muscle mass loss. Increasing evidence from animal studies suggests that the pituitary hormone oxytocin has trophic effects on skeletal muscle cells and can induce weight loss. We piloted a clinical trial testing whether intranasal oxytocin would decrease adiposity without lowering muscle mass in older adults with sarcopenic obesity. Twenty-one older (≥60years), obese (30-43kg/m2), sedentary (&lt;2 strenuous exercises/week) adults with slow gait speed (&lt;1m/sec) were randomized to intra-nasal oxytocin (24IU four times/day) or placebo for 8 weeks. Pre and post body mass index (BMI), 2-hour oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), short physical performance battery (SPPB), and whole body lean and fat mass (via dual-energy X-ray absorptiometry) were assessed. Generalized estimation equation method was used to evaluate effects of oxytocin on these continuous measures. At baseline, results were: age 67.5±5.4years, 71% female, BMI 36.0±3.6kg/m2, HbA1c 5.7±0.4%, 2-hr OGTT glucose 140.8±4.1mg/dL, SPPB 9.2±1.9, fat mass 45,429±7,037g, and lean mass was 49,892±10,470g. From baseline to follow-up, total lean mass increased significantly (2,250g) in the oxytocin group (pre- vs. post-treatment difference of -690g in placebo and +1,559g in oxytocin, p&lt;0.01). Oxytocin did not lead to significant changes in other measures. This data suggests that oxytocin leads to significant improvement in whole body lean mass. Future studies in a larger study population will help determine whether older adults with sarcopenic obesity may benefit from intranasal oxytocin to improve lean muscle mass and physical function.