Search

Background: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear., Objective: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism., Design: Secondary analysis of a randomized, double-blind, placebo-controlled trial., Setting: Veterans Affairs Medical Center., Participants: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty., Interventions: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months., Outcome Measures: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score., Results: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02)., Conclusion: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Background: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m 2 ) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement., Results: Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2 =  0.301 to 0.448, HGS: R 2 =  0.346 to 0.472, FM%: R 2 =  0.299 to 0.432) ( p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05)., Conclusion: These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Gregori, Paudyal, Barnouin, Celli, Segoviano-Escobar, Armamento-Villareal, Napoli, Qualls and Villareal.)

Objective: Lifestyle intervention is recommended as first-line treatment of diabetes at all ages; however, little is known about the efficacy of lifestyle intervention in older adults with diabetes. We aimed to determine whether lifestyle intervention would improve glycemic control and age-relevant outcomes in older adults with diabetes and comorbidities., Research Design and Methods: A total of 100 older adults with diabetes were randomly assigned to 1-year intensive lifestyle intervention (ILI) (diet and exercise at a facility transitioned into community-fitness centers and homes) or healthy lifestyle (HL) group. The primary outcome was change in HbA1c. Secondary outcomes included glucoregulation, body composition, physical function, and quality of life. Changes between groups were analyzed with mixed-model repeated-measures ANCOVA following the intention-to-treat principle., Results: HbA1c improved more in the ILI than the HL group (mean ± SE -0.8 ± 0.1 vs. 0.1 ± 0.1%), associated with improved insulin sensitivity (1.2 ± 0.2 vs. -0.4 ± 0.2) and disposition (26.0 ± 8.9 vs. -13.0 ± 8.4 109 min-1) indices (between-group P < 0.001 to 0.04). Body weight and visceral fat decreased more in the ILI than HL group (-8.4 ± 0.6 vs. -0.3 ± 0.6 kg, P < 0.001, and -261 ± 29 vs. -30 ± 27 cm3, P < 0.001, respectively). Physical Performance Test score increased more in the ILI than HL group (2.9 ± 0.6 vs. -0.1 ± 0.4, P < 0.001) as did VO2peak (2.2 ± 0.3 vs. -1.2 ± 0.2 mL/kg/min, P < 0.001). Strength, gait, and 36-Item Short Form Survey (SF-36) Physical Component Summary score also improved more in the ILI group (all P < 0.001). Total insulin dose decreased in the ILI group by 19.8 ± 4.4 units/day. Adverse events included increased episodes of mild hypoglycemia in the ILI group., Conclusions: A lifestyle intervention strategy is highly successful in improving metabolic and functional health of older adults with diabetes., (© 2022 by the American Diabetes Association.)

Background: Both obesity and hypogonadism are common in older men which could additively exacerbate age-related declines in cognitive function. However, little is known about the effects of lifestyle intervention plus testosterone replacement therapy in this population., Objectives: In this secondary analysis of the LITROS (Lifestyle Intervention and Testosterone Replacement in Obese Seniors) trial, we examined whether testosterone replacement therapy would improve cognitive function when added to intensive lifestyle intervention in older men with obesity and hypogonadism., Methods: Eighty-three older, obese hypogonadal men with frailty were randomly assigned to lifestyle therapy (weight management and exercise training) plus testosterone (LT + Test) or lifestyle therapy plus placebo (LT + Pbo) for 6 mo. For this report, the primary outcome was change in the global cognition composite z score. Secondary outcomes included changes in z score subcomponents: attention/information processing, memory, executive function, and language. Changes between groups were analyzed using mixed-model repeated-measures ANCOVAs following the intention-to-treat principle., Results: Global cognition z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.49 compared with 0.21; between-group difference: -0.28; 95% CI: -0.45, -0.11; Cohen's d = 0.74). Moreover, attention/information z score and memory z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.55 compared with 0.23; between-group difference: -0.32; 95% CI: -0.55, -0.09; Cohen's d = 0.49 and mean change: 0.90 compared with 0.37; between-group difference: -0.53; 95% CI: -0.93, -0.13; Cohen's d = 1.43, respectively). Multiple regression analyses showed that changes in peak oxygen consumption, strength, total testosterone, and luteinizing hormone were independent predictors of the improvement in global cognition (R2 = 0.38; P < 0.001)., Conclusions: These findings suggest that in the high-risk population of older men with obesity and hypogonadism, testosterone replacement may improve cognitive function with lifestyle behaviors controlled via lifestyle intervention therapy.This trial was registered at clinicaltrials.gov as NCT02367105., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background: Obesity and hypogonadism additively contribute to frailty in older men; however, appropriate treatment remains controversial., Objective: Determine whether testosterone replacement augments the effect of lifestyle therapy on physical function in older men with obesity and hypogonadism., Design: Randomized, double-blind, placebo-controlled trial., Setting: VA Medical Center., Participants: 83 older (age ≥65 years) men with obesity (body mass index ≥30 kg/m2) and persistently low am testosterone (<10.4 nmol/L) associated with frailty., Interventions: Participants were randomized to lifestyle therapy (weight management and exercise training) plus either testosterone (LT+Test) or placebo (LT+Pbo) for 6 months., Outcome Measures: Primary outcome was change in Physical Performance Test (PPT) score. Secondary outcomes included other frailty measures, body composition, hip bone mineral density (BMD), physical functions, hematocrit, prostate specific antigen (PSA), and sex hormones., Results: PPT score increased similarly in LT+Test and LT+Pbo group (17% vs. 16%; P = 0.58). VO2peak increased more in LT+Test than LT+Pbo (23% vs. 16%; P = 0.03). Despite similar -9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (-2% vs. -3%; P = 0.01 and -2% vs -4%; P = 0.04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.5% vs -1.1%; P = 0.003). Strength increased similarly in LT+Test and LT+Pbo (23% vs 22%; P = 0.94). Hematocrit but not PSA increased more in LT+Test than LT+Pbo (5% vs 1%; P < 0.001). Testosterone levels increased more in LT+Test than LT+Pbo (167% vs 27%; P < 0.001)., Conclusion: In older, obese hypogonadal men, adding testosterone for 6 months to lifestyle therapy does not further improve overall physical function. However, our findings suggest that testosterone may attenuate the weight loss-induced reduction in muscle mass and hip BMD and may further improve aerobic capacity., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorphism (rs56061981) that altered methylation at one of these CpG sites further associated with working memory performance in 2 independent aging cohorts. Studying prefrontal cortex samples, we found higher CXCL10 protein levels in those with Alzheimer's disease, compared with aged controls. These findings support the association of peripheral inflammation, as demonstrated by CXCL10, in aging and cognitive decline. We reveal age-related epigenetic and genetic factors which contribute to the dysregulation of CXCL10., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres., Methods: Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity., Results: There was no significant age-related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people., Conclusions: The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age-related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

The aim of this study was to compare postural sway during a series of static balancing tasks and during five chair rises between healthy young (mean [SEM], age 26 [1] years), healthy old (age 67 [1] years) and master athlete runners (age 67 [1] years; competing and training for the previous 51 [5] years) using the Microsoft Kinect One. The healthy old had more sway than the healthy young in all balance tasks. The master athletes had similar sway to young athletes during two-leg balancing and one-leg standing with eyes open. When balancing on one leg with eyes closed, both the healthy old and the master athletes had around 17-fold more sway than the young athletes. The healthy old and master athletes also had less anterio-posterior movement during chair rising compared with young athletes. These results suggest that masters runners are not spared from the age-associated decline in postural stability and may benefit from specific balance training.

Introduction: Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes., Materials and Methods: Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl. Areal BMD (aBMD) was measured by DXA; volumetric BMD (vBMD) and bone geometry by peripheral-quantitative-computed-tomography; serum C-telopeptide (CTX), osteocalcin, sclerostin and sex hormone-binding globulin (SHBG) by ELISA, testosterone and 25-hydroxyvitamin D (25OHD) by automated immunoassay and estradiol by liquid-chromatography/mass-spectrometry. Groups were compared by ANOVA adjusted for covariates., Results: One-hundred five men, 49 with and 56 without diabetes were enrolled. Adjusted vBMD at 38% tibia was higher in diabetic than non-diabetic men (857.3±69.0mg/cm 3 vs. 828.7±96.7mg/cm 3 , p=0.02). Endosteal (43.9±5.8mm vs. 47.1±7.8mm, p=0.04) and periosteal (78.4±5.0mm vs. 81.3±6.5mm, p=0.02) circumferences and total area (491.0±61.0mm 2 vs. 527.7±87.2mm 2 , p=0.02) at 38% tibia, were lower in diabetic men even after adjustments for covariates. CTX (0.25±0.14ng/ml vs. 0.40±0.19ng/ml, p<0.001) and osteocalcin (4.8±2.8ng/ml vs. 6.8±3.5ng/ml, p=0.006) were lower in diabetic men; there were no differences in sclerostin and 25OHD. Circulating gonadal hormones were comparable between the groups., Conclusion: Among hypogonadal men, those with T2D have higher BMD, poorer bone geometry and relatively suppressed bone turnover. Studies with larger sample size are needed to verify our findings and possible even greater risk for fractures among hypogonadal diabetic men., (Published by Elsevier Inc.)

It is thought that the prime determinant of global muscle capillary density is the mean oxidative capacity. However, feedback control during maturational growth or adaptive remodelling of local muscle capillarisation is likely to be more complex than simply matching O2 supply and demand in response to integrated tissue function. We tested the hypothesis that the maximal oxygen consumption (MO2,max) supported by a capillary is relatively constant, and independent of the volume of tissue supplied (capillary domain). We demonstrate that local MO2,max assessed by succinate dehydrogenase histochemistry: (1) varied more than 100-fold between individual capillaries and (2) was positively correlated to capillary domain area in both human vastus lateralis (R=0.750, P<0.001) and soleus (R=0.697, P<0.001) muscles. This suggests that, in contrast to common assumptions, capillarisation is not primarily dictated by local oxidative capacity, but rather by factors such as fibre size, or consequences of differences in fibre size such as substrate delivery and metabolite removal., (© 2015. Published by The Company of Biologists Ltd.)

Background: Muscle mass, strength, and power are known determinants of mobility in older adults but there is limited knowledge on the influence of muscle architecture or tendon properties on mobility. The purpose of this study was to examine the relationship between mobility and plantarflexor muscle-tendon properties in healthy older adults., Methods: A total of 52 subjects (age 70-81 years) were measured for 6-minute walk test (6MWT), timed "up and go"-test (TUG), isometric plantarflexion strength, Achilles tendon stiffness, triceps surae muscle architecture, lower extremity lean mass, isometric leg extension strength, and leg extension power. Partial correlations and multivariate regression models adjusted for sex, age, body mass, and height were used to examine the relationship between mobility (6MWT and TUG) and lower limb muscle-tendon properties., Results: Multivariate regression models revealed that Achilles tendon stiffness (p = .020), plantarflexion strength (p = .022), and medial gastrocnemius fascicle length (p = .046) were independently associated with 6MWT. Plantarflexion strength (p = .037) and soleus fascicle length (p = .031) were independently associated with TUG., Conclusions: Plantarflexor muscle-tendon properties were associated with mobility in older adults independent of lower extremity lean mass, leg extension strength, or power. Plantarflexion strength was a stronger predictor of mobility than leg extension strength or power. The novel finding of this study was that muscle architecture and tendon properties explained interindividual differences in mobility. This study highlights the importance of the plantarflexors for mobility in older adults and provides understanding of possible mechanisms of age-related decline in mobility., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Muscle mass is particularly relevant to follow during aging, owing to its link with physical performance and autonomy. The objectives of this work were to assess muscle volume (MV) and intramuscular fat (IMF) for all the muscles of the thigh in a large population of young and elderly healthy individuals using magnetic resonance imaging (MRI) to test the effect of gender and age on MV and IMF and to determine the best representative slice for the estimation of MV and IMF. The study enrolled 105 healthy young (range 20-30 years) and older (range 70-80 years) subjects. MRI scans were acquired along the femur length using a three-dimension three-point Dixon proton density-weighted gradient echo sequence. MV and IMF were estimated from all the slices. The effects of age and gender on MV and IMF were assessed. Predictive equations for MV and IMF were established using a single slice at various femur levels for each muscle in order to reduce the analysis process. MV was decreased with aging in both genders, particularly in the quadriceps femoris. IMF was largely increased with aging in men and, to a lesser extent, in women. Percentages of MV decrease and IMF increase with aging varied according to the muscle. Predictive equations to predict MV and IMF from single slices are provided and were validated. This study is the first one to provide muscle volume and intramuscular fat infiltration in all the muscles of the thigh in a large population of young and elderly healthy subjects.

Purpose: To propose a manual segmentation method for individual quadriceps femoris (QF) muscles and to test its reliability for muscle volume estimation., Materials and Methods: Images were acquired every 5 mm along the thigh using a 3T MRI scanner on 10 young (mean age: 25 years) and 10 older (mean age: 75 years) adults using a three-point 3D Dixon sequence. In each slice, anatomical cross-sectional areas of the individual quadriceps muscles of the dominant leg were outlined by two operators working independently. Differences between operators were assessed by means of Bland-Altman plots and intraclass correlation coefficients (ICC). This study was approved by the local Ethics Committee., Results: Precise delimitation of individual muscles along the femur often remains challenging, particularly near their insertion areas where some muscles may be partially or totally fused. There was, however, an excellent interoperator segmentation reliability despite a systematic significant difference between operators (ICC > 0.99), mainly due to delineation divergences. Considering all subjects and muscles, differences between operators were all lower than 4.4%., Conclusion: This work has demonstrated the excellent reliability of manual segmentation to assess cross-sectional areas and therefore the volume of individual QF muscles using MRI. It may serve as a basis for a future segmentation consensus of the QF muscles., (© 2013 Wiley Periodicals, Inc.)

Within the European multi-centre MyoAge project, one workpackage was designed to investigate the contribution of age-related changes to muscle mass, contractile characteristics and neural control in relation to reductions in mobility in older age. The methodology has been described here. Test centres were located in Manchester, UK; Paris, France; Leiden, The Netherlands; Tartu, Estonia and Jyväskylä, Finland. In total, 182 young (18-30 years old, 52.2 % female) and 322 older adults (69-81 years old, 50 % female) have been examined. The participants were independent living, socially active and free from disease that impaired mobility levels. The older participants were selected based on physical activity levels, such that half exceeded current recommended physical activity levels and the other half had lower physical activity levels than is recommended to maintain health. Measurements consisted of blood pressure; anthropometry and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging); lung function; standing balance and cognitive function (CANTAB). Mobility was assessed using the Timed Up and Go, a 6 min walk, activity questionnaires and accelerometers to monitor habitual daily activities. Muscle strength, power, fatigue and neural activation were assessed using a combination of voluntary and electrically stimulated contractions. Fasting blood samples and skeletal muscle biopsies were collected for detailed examination of cell and molecular differences between young and older individuals. The results from this study will provide a detailed insight into "normal, healthy" ageing, linking whole-body function to the structure and function of the neuromuscular system and the molecular characteristics of skeletal muscle.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.