Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial-mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±SD) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3-fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)-positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage-dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial-mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.

Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery& Transcatheter Interventions; NCT01845207).

No abstract

It is unclear whether mandibular implant overdentures improve the nutritional state of edentulous patients better than conventional dentures. In a randomized clinical trial, we tested for post-treatment differences in nutritional status between patients with mandibular two-implant retained overdentures and those with conventional complete dentures. Edentulous subjects (ages 65-75 yrs) received two-implant mandibular overdentures (IOD, n = 30) or conventional dentures (CD, n = 30). Measures of nutritional state were gathered before and 6 mos after treatment. Significant improvements in anthropometric parameters were detected in the IOD but not in the CD group, for percent body fat (p = 0.011) and skin-fold thickness at the biceps, subscapularis, and abdomen (p < 0.05), with significant decreases in waist circumference (p < 0.0001) and waist-hip ratio (p = 0.001). Significant increases were seen in concentrations of serum albumin (p = 0.015), hemoglobin (p = 0.01), and B12 (p = 0.01). No significant between-group differences were found. These results suggest that low-cost IOD treatment may improve the nutritional state of edentulous people.

HGS is independently associated with survival and important biological, functional, and quality of life characteristics in advanced cancer patients. Patients presenting with very low percentiles with respect to their handgrip assessment may require timely referral to supportive and/or palliative care services.

BackgroundAlthough exertional fatigue is directly and negatively related to skeletal muscle mass and strength, it is currently unknown if these variables are associated with cancer-related fatigue (CRF). Therefore, the purpose of this study was to determine if CRF is associated with measures of appendicular lean muscle mass and strength in advanced cancer patients (ACP).Methods and resultsEighty-four patients (48 men, 36 women aged 61.6 ± 13.2 year) newly diagnosed (≤6 months) with inoperable (Stages III–IV) gastrointestinal or non-small cell lung cancer participated in this study. All patients completed the Brief Fatigue Inventory (BFI). Handgrip (HGS) and quadriceps (QS) strength were assessed using isometric and isokinetic dynamometry, respectively. Skeletal muscle mass index (SMMI) was calculated from the appendicular lean mass measured via dual-energy X-ray absorptiometry divided by body height squared. Univariate analysis showed BFI to be significantly associated with body mass index, weight loss, anemia, hypoalbuminemia, activity level, pain, depression, and sarcopenia along with SMMI, HGS, and QS. HGS (r = −0.34; p = 0.018), QS (r = −0.39; p = 0.024), and SMMI (r = −0.60; p < 0.001) were negatively correlated with BFI total scores in men but not in women. When adjusted for sex, age, diagnosis, survival, along with the above characteristics, multivariate analyses showed that BFI scores were negatively associated with HGS (B = −0.90; 95% CI −1.5:−0.3), QS (−0.2; −0.3:−0.01), and SMMI (−7.5; −13.0:−2.0). There was a significant sex × SMMI interaction (10.8; 1.2:20.5), where BFI decreased with increasing SMMI in men, but did not change with SMMI in women.ConclusionThese results suggest that in ACP, CRF is related to muscle mass and strength, which may provide targets for future interventions.

OBJECTIVE-We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it. RESEARCH DESIGN AND METHODS-Hyperinsulinemic(ϳ570 pmol/l), euglycemic (5.5 mmol/l), and isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic type 2 diabetic subjects and 23 subjects without diabetes matched for age and body composition, after 7 days on a inpatient, protein-controlled, isoenergetic diet. Glucose and leucine kinetics were determined using tracers.RESULTS-In type 2 diabetes, postabsorptive (baseline) glycemia was 8 -9 mmol/l, glucose production (R a ) and disposal (R d ) were elevated, and once clamped, endogenous glucose R a remained greater and R d was less (P Ͻ 0.05) than in control subjects. Baseline leucine kinetics did not differ despite higher insulin levels. The latter was an independent predictor of leucine flux within each sex. With clamp, total flux increased less (P ϭ 0.016) in type 2 diabetic men, although protein breakdown decreased equally (ϳ20%) in male groups but less in female groups. Whereas protein synthesis increased in male control subjects and in both female groups, it did not in male subjects with type 2 diabetes. In men, homeostasis model assessment of insulin resistance predicted 44%, and, in women, waist-to-hip ratio predicted 40% of the change in synthesis. T here is clear evidence for altered protein metabolism in type 1 diabetes (1-5), but in type 2 diabetes, results have been inconsistent. That protein metabolism in type 2 diabetes has been reported to be both unaffected and altered may stem from differences in study design: tracer method, adiposity, and sex of subjects; prevailing glycemia; normalization of data; and types of statistical analyses. We reported accelerated integrated fed-fasted kinetics of whole-body protein metabolism (using [ 15 N]glycine) in obese type 2 diabetic subjects with hyperglycemia (6 -9) compared with obese control subjects (6,7). Such studies required adjusting data for fat-free mass (FFM), sex, and age (6,8,9) and had precise control of protein and energy intake. When glycemic control was normalized with insulin (7), improved with oral antihyperglycemic agents (6), or normalized with oral agents and energy restriction (6), protein turnover was either improved or not different from that of obese control subjects. CONCLUSIONS-DuringMost reports showing no alterations in type 2 diabetes (10 -14) assessed postabsorptive and postinsulin states using amino acid tracers. However, one reported elevated postabsorptive catabolism in hyperglycemic type 2 diabetic patients, not corrected by prior insulin treatment (15). Another showed elevated rates of leucine transamination that decreased with better glycemic control, without altering leucine oxidation (16)....

Our results suggest that greater protein intakes and a more even distribution across meals are modifiable factors associated with higher muscle mass in older adults but not with losses over 2 y. Interventional studies should determine longer-term effects on preserving LM with aging.