The primary mechanism that contributes to decreasing skeletal muscle strength and size with healthy aging is not presently known. This study examined the contribution of the ubiquitin-proteasome pathway and apoptosis to skeletal muscle wasting in older adults (n = 21; mean age = 72.76 +/- 8.31 years) and young controls (n = 21; mean age = 21.48 +/- 2.93 years). Subjects underwent a percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3) individual fiber type and cross-sectional area. In addition, a whole muscle strength test was also performed. A one-way ANOVA revealed significant increases in the number of positive TUNEL cells in older adults (87%; p < 0.05), although no significant increase in caspase-3/7 activity was detected. Additionally, ubiquitin ligase gene expression, individual muscle fiber type and CSA were not different between old and young subjects. Muscle strength was also significantly lower in old compared to young subjects (p < 0.05). In conclusion, this study indicates a preferential role for apoptosis contributing to decreases in muscle function with age.

GODARD, MICHAEL P., BRAD A. JOHNSON, AND SCOTT R. RICHMOND. Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men. Obes Res. 2005;13:1335-1343. Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI Ն 26 kg/m 2 ) men. Research Methods and Procedure: Thirty subjects (forskolin, n ϭ 15; placebo, n ϭ 15) were studied in a randomized, double-blind, placebo-controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p Յ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p Յ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p ϭ 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p Յ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 Ϯ 33.77% in the forskolin group compared with a decrease of 1.08 Ϯ 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12-week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.

Richmond, S.R., and M.P. Godard. The effects of varied rest periods between sets to failure using the bench press in recreationally trained men. J. Strength Cond. Res. 18(4): 000-000. 2004.-The purpose of this study was to determine the rate of recovery for recreational weight trainers between 2 sets of bench press to volitional exhaustion. Twenty-eight men performed 2 sets of the bench press at 75% of their previously determined 1 repetition maximum (1RM) to volitional exhaustion. Rest periods of 1, 3, or 5 minutes between sets were utilized on the 3 separate testing days. There was a significant decrease in the number of repetitions performed between the second sets at all rest periods. There were no significant differences in work performed (repetitions ϫ weight) during the second set with the 3-and 5-minute rest periods, but the total work with a 1-minute rest period (1,389.1 Ϯ 529.9) was significantly less than both the 3-(1,494.9 Ϯ 451.0) and 5-minute (1,711.4 Ϯ 478.0) rest period. The data indicated that subjects were unable to fully recover between the first and second sets of maximal resistance exercise, regardless of the rest period. However, subjects were able to maintain a performance level of 8-12 repetitions and sustain the total work performed per set with as little as 3 minutes rest between sets.

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

Persistent overexpression of IGF-I in mice skeletal muscle results in hypertrophy, which is likely mediated via the mTOR/p70S6K pathway, potentially via an Akt-independent signaling pathway.