Denervation leads to significant muscle atrophy, but it is less clear whether 1) loss of capillaries, fibre size and oxidative capacity decline in parallel and 2) the time course of these changes differs between young and old animals. To investigate this, we denervated the left gastrocnemius muscle for 1, 2 or 4 weeks, while the right muscle served as an internal control, in rats that were 5 or 25 months old at the end of the experiment. In the fast part of the gastrocnemius muscle, almost all atrophy had occurred after two weeks (42%) of denervation. Even after 4 weeks of denervation, there was no significant reduction in the oxidative capacity of the muscle. Significant capillary loss occurred only after 4 weeks of denervation (P < 0.001) that lagged behind and was less than proportional to the decrease in fibre size. Consequently, the capillary density was elevated (P < 0.001). The time course of these morphological changes was similar in the 5- and 25-month-old rats. Comparing these data with those previously published in the soleus muscle from the same animals show that the decrease in oxidative capacity and capillary rarefaction were more pronounced and occurred earlier than in the gastrocnemius muscle, respectively. The time course of capillary loss lagged behind the decrease in fibre size, and combined with the absence of denervation-induced changes in oxidative capacity this resulted in a muscle capillary supply in excess of that expected by the metabolism and fibre size at least during the first 4 weeks after denervation.

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 (&lt;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 &lt; 0.001). Testosterone levels increased more in LT+Test than LT+Pbo (167% vs 27%; P &lt; 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.

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 &lt; 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.