Michaela C. Devries

The Effect of Aging on Human Skeletal Muscle Mitochondrial and Intramyocellular Lipid Ultrastructure

The purpose of this study was to determine whether ultrastructural changes in intramyocellular lipid (IMCL) and mitochondria occur with aging. Muscle samples were analyzed from 24 young and 20 old, equally active, individuals for IMCL and mitochondria quantity and size as well as their association. Old men had larger IMCL droplets than all other groups in the total muscle area. Old individuals showed higher IMCL content in the subsarcolemmal area. Young participants had a greater number of mitochondria compared with old participants in both fiber regions and greater enzyme activities of cytochrome c oxidase and citrate synthase. The fraction of IMCL touching mitochondria was lowest in old women in the total area and in old men in the subsarcolemmal region. In summary, older adults have larger IMCL droplets, fewer mitochondria, and a lower proportion of IMCL in contact with mitochondria. These factors likely contribute to age-related reductions in mitochondrial function and lipid metabolism.

Effects of high‐intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis

The G93A transgenic mouse has a mutation in copper/zinc superoxide dismutase (CuZnSOD) that results in oxidative stress and motor neuron loss. Endurance exercise training is known to increase antioxidant capacity in skeletal muscle. Therefore, we hypothesized that endurance training may extend onset of disease or survival in the G93A mouse. We examined the effects of high‐intensity endurance exercise training (45 min/day, 5 times/week, progressive increase from 9 to 22 m/min) on disease onset and survival in G93A mice. Endurance training did not affect clinical onset, although it hastened death in male mice (P < 0.05). Endurance‐trained males had a statistically significant decrease in rotarod performance at 112 days (P < 0.05), whereas sedentary males decreased at 119 days (P < 0.05). Endurance‐trained and sedentary females decreased at 126 days and 129 days, respectively (P < 0.05). Female mice lived longer than males (P < 0.05), and there was a trend for hastened clinical onset in males (P = 0.062). We conclude that high‐intensity endurance exercise training does not affect onset of clinical symptoms in G93A mice but hastens a decrease in motor performance and death following onset of clinical symptoms in male mice only. In light of a recent report describing increased survival following low‐intensity endurance training, it appears that training intensity is an important determinant of survival in the G93A mouse.

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long‐term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, α‐lipoic acid, and β‐hydroxy‐β‐methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four‐compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD. Muscle Nerve, 2005

Endurance training without weight loss lowers systemic, but not muscle, oxidative stress with no effect on inflammation in lean and obese women.

Obesity is associated with oxidative stress. Endurance training (ET) in healthy individuals increases antioxidant enzyme activity and decreases oxidative stress, whereas its effects on oxidative status in obese humans have yet to be determined. We investigated the effects of obesity and ET on markers of oxidative stress, antioxidant defense, and inflammation. Obese (n=12) and lean (n=12) women underwent 12 weeks of ET with blood, 24-h urine, and muscle biopsies collected prior to and following training for determination of oxidative stress (urinary 8-hydroxy-2-deoxyguanosine and 8-isoprostanes, muscle protein carbonyls, and 4-hydroxynonenal), antioxidant enzyme protein content (muscle CuZnSOD, MnSOD, and catalase), and inflammation (C-reactive protein, leptin, adiponectin, interleukin-6). Obese women had elevated urinary 8-hydroxy-2-deoxyguanosine (P=0.03), muscle protein carbonyls (P=0.03), and 4-hydroxynonenal (P<0.001); serum C-reactive protein (P=0.01); and plasma leptin (P=0.0001) and interleukin-6 (P=0.03). ET decreased urinary 8-hydroxy-2-deoxyguanosine (P=0.006) and 8-isoprostanes (P=0.02) in all subjects and CuZnSOD protein content (P=0.04) in obese women, in the absence of changes in body weight or composition. ET without weight loss decreases systemic oxidative stress, but not markers of inflammation, in obese women.

Follow-up for women after treatment for cervical cancer: A systematic review

OBJECTIVE To determine the optimal recommended program for the follow-up of patients who are disease free after completed primary therapy for cervical cancer. METHODS Systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980-November 2007). RESULTS Seventeen retrospective trials were identified. Most studies reported similar intervals for follow-up and ranged from a low of 9 visits to a high of 28 visits over 5 years. Follow-up visits typically occurred once every 3-4 months for the first 2 years, every 6 months for the next 3 years and then annually until year 10. All 17 trials reported that a physical exam was performed at each visit. Vaginal vault cytology was analyzed in 13 trials. Other routine surveillance tests included chest x-ray, ultrasound, CT scans, MRI, intravenous pyelography and tumour markers. Median time to recurrence ranged from 7-36 months after primary treatment. Rates of recurrence ranged from 8-26% with 14-57% of patients recurring in the pelvis, and 15-61% of patients recurring at distant or multiple sites. Of the 8-26% of patients who experienced disease recurrence, the vast majority, 89-99%, had recurred by year 5. Upon recurrence, median survival was 7-17 months. Asymptomatic recurrent disease was detected using physical exam in 29-71%, chest x-ray in 20-47%, CT in 0-34% and vaginal vault cytology in 0-17% of patients, respectively. CONCLUSION There is modest low quality evidence to inform the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease free after receiving primary treatment. Follow-up visits should include a complete physical examination whereas, frequent vaginal vault cytology does not add significantly to the detection of early disease recurrence. Patients should return to annual population-based screening after 5 years of recurrence-free follow-up.

Effect of Endurance Exercise on Hepatic Lipid Content, Enzymes, and Adiposity in Men and Women

Obesity and physical inactivity are independent risk factors for the development of nonalcoholic fatty liver disease (NAFLD). We determined the effect of endurance exercise training on hepatic lipid content and hepatic enzyme concentration in men and women. Waist circumference (WC), percent body fat (BF), computed tomography (CT) scans for liver attenuation (inverse relationship with hepatic lipid), bilirubin, alanine aminotransferase (ALT), and γ‐glutamyltransferase (GGT) plasma concentrations were measured before and after 12 weeks of endurance training in 41 lean and obese men and women. Exercise training did not change liver attenuation, body weight, percent BF, bilirubin, or ALT concentration, but did lower WC (P < 0.0001), and decreased GGT in men only (P = 0.01). Obese subjects had a lower liver attenuation than lean subjects (P = 0.04). Obese women had lower ALT than obese men (P = 0.03). GGT was lower in women before and after training. WC was positively correlated with GGT (r = 0.32, P = 0.003) and ALT (r = 0.320, P = 0.004) and negatively correlated with liver attenuation (r = −0.340, P = 0.03). Percent BF was negatively correlated with bilirubin (r = −0.374, P = 0.005). Liver attenuation was negatively correlated with ALT (r = −0.405, P = 0.003). Short‐term endurance training without weight loss does not alter hepatic lipid content. There was a strong relationship between GGT/ALT and body composition (percent BF) as well as between ALT and hepatic lipid content.

Supplemental Protein in Support of Muscle Mass and Health: Advantage Whey

Skeletal muscle is an integral body tissue playing key roles in strength, performance, physical function, and metabolic regulation. It is essential for athletes to ensure that they have optimal amounts of muscle mass to ensure peak performance in their given sport. However, the role of maintaining muscle mass during weight loss and as we age is an emerging concept, having implications in chronic disease prevention, functional capacity, and quality of life. Higher-protein diets have been shown to: (1) promote gains in muscle mass, especially when paired with resistance training; (2) spare muscle mass loss during caloric restriction; and (3) attenuate the natural loss of muscle mass that accompanies aging. Protein quality is important to the gain and maintenance of muscle mass. Protein quality is a function of protein digestibility, amino acid content, and the resulting amino acid availability to support metabolic function. Whey protein is one of the highest-quality proteins given its amino acid content (high essential, branched-chain, and leucine amino acid content) and rapid digestibility. Consumption of whey protein has a robust ability to stimulate muscle protein synthesis. In fact, whey protein has been found to stimulate muscle protein synthesis to a greater degree than other proteins such as casein and soy. This review examines the existing data supporting the role for protein consumption, with an emphasis on whey protein, in the regulation of muscle mass and body composition in response to resistance training, caloric restriction, and aging.

Creatine supplementation during resistance training in older adults-a meta-analysis.

INTRODUCTION Age-related sarcopenia and dynapenia have negative effects on strength and the ability to perform activities of daily living. Resistance training (RT) increases muscle mass and strength in older adults and is an established countermeasure for sarcopenia and dynapenia, and creatine may enhance this effect. We aimed to determine whether the addition of Cr to RT increased gains in muscle mass, strength, and function in older adults over RT alone by conducting a systematic review and meta-analysis. METHODS PubMed and Healthstar databases were searched. Randomized, placebo-controlled trials that involved older adults supplemented with Cr and included RT regimens (>6 wk) were included. Data were analyzed using fixed or random (if data were heterogeneous) effects meta-analysis using RevMan 5. RESULTS The meta-analysis comprised 357 older adults (average ± SD Cr: 63.6 ± 5.9 yr, Pl: 64.2 ± 5.4 yr) with 12.6 ± 4.9 wk of RT. Cr + RT increased total body mass (P = 0.004) and fat-free mass (P < 0.0001) with no effect on fat mass as compared with RT alone. Cr + RT increased chest press (P = 0.004) and leg press (P = 0.02) one-repetition maximum to a greater extent than RT alone, with no difference in the effect on knee extension or biceps curl one-repetition maximum, isokinetic or isometric knee extension peak torque. Cr + RT had a greater effect than RT alone on the 30-s chair stand test (P = 0.03). CONCLUSION Retention of muscle mass and strength is integral to healthy aging. The results from this meta-analysis are encouraging in supporting a role for Cr supplementation during RT in healthful aging by enhancing muscle mass gain, strength, and functional performance over RT alone; however, the limited number of studies indicates further work is needed.

Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial

BACKGROUND A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass (LBM), particularly when combined with exercise. OBJECTIVE The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition. DESIGN We used a single-blind, randomized, parallel-group prospective trial. During a 4-wk period, we provided hypoenergetic (~40% reduction compared with requirements) diets providing 33 ± 1 kcal/kg LBM to young men who were randomly assigned (n = 20/group) to consume either a lower-protein (1.2 g · kg(-1) · d(-1)) control diet (CON) or a higher-protein (2.4 g · kg(-1) · d(-1)) diet (PRO). All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk. A 4-compartment model assessment of body composition was made pre- and postintervention. RESULTS As a result of the intervention, LBM increased (P < 0.05) in the PRO group (1.2 ± 1.0 kg) and to a greater extent (P < 0.05) compared with the CON group (0.1 ± 1.0 kg). The PRO group had a greater loss of fat mass than did the CON group (PRO: -4.8 ± 1.6 kg; CON: -3.5 ± 1.4kg; P < 0.05). All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation. Changes in serum cortisol during the intervention were associated with changes in body fat (r = 0.39, P = 0.01) and LBM (r = -0.34, P = 0.03). CONCLUSIONS Our results showed that, during a marked energy deficit, consumption of a diet containing 2.4 g protein · kg(-1) · d(-1) was more effective than consumption of a diet containing 1.2 g protein · kg(-1) · d(-1) in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise. Changes in serum cortisol were associated with changes in body fat and LBM, but did not explain much variance in either measure. This trial was registered at clinicaltrials.gov as NCT01776359.

Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men

Step‐reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding‐induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate muscle anabolic resistance accompanying SR. We used a unilateral leg model to compare older subjects’ who had undergone SR to a loaded condition of SR plus RT (SR + RT). Thirty older men (70 ± 1 years) underwent 14 days of SR (<1500 steps/day) with supplementation of either 5 g/day CIT or glycine placebo. Throughout SR, subjects performed unilateral low‐load RT thrice weekly. We assessed muscle protein synthesis in the postabsorptive and postprandial state (20 g whey isolate plus 15 g glycine or as micellar‐whey with 5 g CIT or 15 g glycine, n = 10/group). As MPS was similar after ingestion of either whey isolate, micellar‐whey, or micellar‐whey + CIT data related to different dietary groups were collapsed to compare SR and SR + RT legs. Subjects’ daily steps were reduced by 80 ± 2% during SR (P < 0.001) compared with baseline. Leg fat‐free mass decreased with SR (−124 ± 61 g) and increased in the SR + RT (+126 ± 68 g; P = 0.003). Myofibrillar FSR was lower (P < 0.0001) in the SR as compared with the SR + RT leg in the postabsorptive (0.026 ± 0.001%/h vs. 0.045 ± 0.001%/h) and postprandial states (0.055 ± 0.002%/h vs. 0.115 ± 0.003%/h). We conclude that low‐load RT, but not supplementation with CIT, can attenuate the deleterious effects of SR in aging muscle.