Bong-Sup Park

Potential mechanisms underlying the role of chronic inflammation in age-related muscle wasting

Sarcopenia, an age-related condition characterized by progressive skeletal muscle degeneration, might exist as one of the primary clinical conditions underlying severe functional impairment as well as increased risk of co-morbidities in the elderly. Although the etiology of sarcopenia remains multifaceted, age-related chronic inflammation has been strongly implicated in muscle wasting and related sequelae during advanced age. Recent evidence suggests that aberrant, unresolved alterations in regular inflammatory processes during advanced age might ultimately operate as the link that drives skeletal muscle to become more degenerative and dysfunctional in nature. Such negative atrophic muscular outcomes might result from inflammation-induced disruption of central mechanisms regulating skeletal muscle morphology and remodeling. In addition, recent findings demonstrate an adverse confluence between sarcopenia and excessive adiposity (i.e. sarcopenic obesity), as the co-existence of such adverse alterations in body composition may exacerbate systemic inflammation and muscle wasting in the elderly. The following evidence-based review serves to examine sarcopenia from a mechanistic perspective with emphasis on chronic inflammation.

Physiological Decrements During Sustained Military Operational Stress

Missions conducted by the U.S. Military during combat involve a multitude of operational stressors that can cause deterioration in physical and military performance of soldiers. Physiological consequences of sustained operational stress include decrements in anabolic hormones, skeletal muscle mass, and loss of bone mineral density. The objective of this review is to examine the current literature and provide commanders with information on the physical and physiological decrements in soldiers conducting sustained operations. The intent is that this will provide commanders with insight on how to plan for missions to incorporate possible countermeasures to enhance or sustain warfighter performance.

HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise

OBJECTIVE To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. MATERIALS/METHODS Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. RESULTS ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. CONCLUSION HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions.

β-hydroxy-β-methylbutyrate did not enhance high intensity resistance training-induced improvements in myofiber dimensions and myogenic capacity in aged female rats

Older women exhibit blunted skeletal muscle hypertrophy following resistance training (RT) compared to other age and gender cohorts that is partially due to an impaired regenerative capacity. In the present study, we examined whether β-hydroxy-β-methylbutyrate (HMB) provision to aged female rodents would enhance regenerative mechanisms and facilitate RT-induced myofiber growth. Nineteen-month old female Sprague-Dawley rats were randomly divided into three groups: HMB (0.48 g/kg/d; n = 6), non-HMB (n = 6), and control (n = 4). HMB and non-HMB groups underwent RT every third day for 10 weeks using a ladder climbing apparatus. Whole body strength, grip strength, and body composition was evaluated before and after RT. The gastrocnemius and soleus muscles were analyzed using magnetic resonance diffusion tensor imaging, RT-PCR, and immunohistochemistry to determine myofiber dimensions, transcript expression, and satellite cells/myonuclei, respectively. ANOVAs were used with significance set at p < 0.05. There were significant time effects (pre vs. post) for whole body strength (+262%), grip strength (+17%), lean mass (+20%), and fat mass (−19%). Both RT groups exhibited significant increases in the mean myofiber cross-sectional area (CSA) in the gastrocnemius and soleus (+8−22%) compared to control. Moreover, both groups demonstrated significant increases in the numbers of satellite cells (+100−108%) and myonuclei (+32%) in the soleus but not the gastrocnemius. A significant IGF-I mRNA elevation was only observed in soleus of the HMB group (+33%) whereas MGF and myogenin increased significantly in both groups (+32−40%). Our findings suggest that HMB did not further enhance intense RT-mediated myogenic mechanisms and myofiber CSA in aged female rats.

Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia.

PURPOSE The appropriate mode of exercise training for cancer cachexia is not well-established. Using the colon-26 (C26) mouse model of cancer cachexia, we defined and compared the skeletal muscle responses to aerobic and resistance training. METHODS Twelve-month old Balb/c mice were initially assigned to control, aerobic training (AT; wheel running), or resistance training (RT; ladder climbing) (n=16-17/group). After 8weeks of training, half of each group was injected with C26 tumor cells, followed by 3 additional weeks of training. Body composition and neuromuscular function was evaluated pre- and post-training. Muscles were collected post-training and analyzed for fiber cross-sectional area (CSA), Akt-mTOR signaling, and expression of insulin-like growth factor-I (IGF-I) and myogenic regulatory factors. RESULTS Total body mass decreased (p<0.05) in C26 (-8%), AT+C26 (-18%), and RT+C26 (-15%) but not control. Sensorimotor function declined (p<0.05) in control (-16%), C26 (-13%), and RT+C26 (-23%) but not AT+C26. Similarly, strength/body weight decreased (p<0.05) in control (-7%), C26 (-21%), and RT+C26 (-10%) but not AT+C26. Gastrocnemius mass/body weight tended to be greater in AT+C26 vs. C26 (+6%, p=0.09). Enlargement of the spleen was partially corrected in AT+C26 (-27% vs. C26, p<0.05). Fiber CSA was lower in all C26 groups vs. control (-32% to 46%, p<0.05); however, the effect size calculated from C26 and AT+C26 was large (+24%, d=1.04). Phosphorylated levels of mTOR in AT+C26 exceeded C26 (+32%, p<0.05). RT+C26 showed greater mRNA expression (p<0.05) of IGF-IEa (+79%) and myogenin (+126%) with a strong tendency for greater IGF-IEb (+127%, p=0.069) vs. CONCLUSIONS Aerobic or resistance training was unable to prevent tumor-induced body weight loss. However, aerobic training may have preserved function, reduced the inflammatory response of the spleen, and marginally rescued muscle mass possibly through activation of mTOR. Aerobic training may therefore have therapeutic value for patients with cancer cachexia. In contrast, resistance training induced the expression of genes associated with muscle damage and repair. This gene response may be supportive of excessive stress generated by high resistance loading in a tumor-bearing state.

Modified Daily Undulating Periodization Model Produces Greater Performance Than a Traditional Configuration in Powerlifters.

Abstract Zourdos, MC, Jo, E, Khamoui, AV, Lee, S-R, Park, B-S, Ormsbee, MJ, Panton, LB, Contreras, RJ, and Kim, J-S. Modified daily undulating periodization model produces greater performance than a traditional configuration in powerlifters. J Strength Cond Res 30(3): 784–791, 2016—The primary aim of this study was to compare 2 daily undulating periodization (DUP) models on one-repetition maximum (1RM) strength in the squat, bench press, deadlift, total volume (TV) lifted, and temporal hormone response. Eighteen male, college-aged (21.1 ± 1.9 years) powerlifters participated in this study and were assigned to one of 2 groups: (a) traditional DUP training with a weekly training order: hypertrophy-specific, strength-specific, and power-specific training (HSP, n = 9) or (b) modified DUP training with a weekly training order: hypertrophy-specific, power-specific, and strength-specific training (HPS, n = 9). Both groups trained 3 nonconsecutive days per week for 6 weeks and performed the squat, bench press, and deadlift exercises. During hypertrophy and power sessions, subjects performed a fixed number of sets and repetitions but performed repetitions until failure at a given percentage during strength sessions to compare TV. Testosterone and cortisol were measured at pretesting and posttesting and before each strength-specific day. Hypertrophy, power, and strength produced greater TV in squat and bench press (p ⩽ 0.05) than HSP, but not for deadlift (p > 0.05). For squat and deadlift, there was no difference between groups for 1RM (p > 0.05); however, HPS exhibited greater increases in 1RM bench press than HSP (p ⩽ 0.05). Effect sizes (ES) showed meaningful differences (ES > 0.50) in favor of HPS for squat and bench press 1RM. Testosterone decreased (p ⩽ 0.05) at weeks 5 and 6 and cortisol decline at weeks 3 and 4. However, neither hormone was different at posttesting compared with pretesting (p > 0.05). Our findings suggest that an HPS configuration of DUP has enhanced performance benefits compared with HSP.

Impact of a Submaximal Warm-Up on Endurance Performance in Highly Trained and Competitive Male Runners.

Purpose: The purpose of this investigation was to examine the effects of a submaximal running warm-up on running performance in male endurance athletes (n = 16, Mage = 21 ± 2 years, MVO2max = 69.3 ± 5.1 mL/kg/min). Method: Endurance performance was determined by a 30-min distance trial after control and submaximal running warm-up conditions in a randomized crossover fashion. The warm-up began with 5 min of quiet sitting, followed by 6 min of submaximal running split into 2-min intervals at speeds corresponding to 45%, 55%, and 65% maximal oxygen consumption (VO2max). A 2-min walk at 3.2 km/hr concluded the 13-min warm-up protocol. For the control condition, participants sat quietly for 13 min. VO2 and heart rate (HR) were determined at Minutes 0, 5, and 13 of the pre-exercise protocol in each condition. Results: At the end of 13 min prior to the distance trial, mean VO2 (warm-up = 14.1 ± 2.2 mL/kg/min vs. control = 5.5 ± 1.7 mL/kg/min) and mean HR (warm-up = 105 ± 11 bpm vs. control = 67 ± 11 bpm) were statistically greater (p < .001) in the warm-up condition compared with the control condition. The distance run did not statistically differ (p = .37) between the warm-up (7.8 ± 0.5 km) and control (7.7 ± 0.6 km) conditions; however, effect size calculation revealed a small effect (d = 0.2) in favor of the warm-up condition. Thus, the warm-up employed may have important and practical implications to determine placing among high-level athletes in close races. Conclusions: These findings suggest a submaximal running warm-up may have a small but critical effect on a 30-min distance trial in competitive endurance athletes. Further, the warm-up elicited increases in physiological variables VO2 and HR prior to performance; thus, a submaximal specific warm-up should warrant consideration.

β-Hydroxy-β-methylbutyrate improves bone properties and attenuates the depression of protein synthesis during a simulated sustained operation.

OBJECTIVES Soldiers lose muscle and bone density during sustained operations. We investigated the impact of β-hydroxy-β-methylbutyrate (HMB) on bone properties, muscle mass, and markers of skeletal muscle regeneration under simulated military sustained operations. METHODS Male mice were divided into four groups (10/group): (1) ALT = ad libitum + trained (1h/d for 3 d/wk); (2) ALTH = ALT + HMB (0.5 g/kg BW/d); (3) C = caloric restricted (-30%) + trained (6h/d, 6d/wk); and (4) CH = C + HMB. Assessments included bone mineral density/content by dual-energy X-ray absorptiometry, muscle wet weight (quadriceps) and expression of selected genes regulating muscle mass and protein turnover. Analysis of variances were used with significance set at p < 0.05. RESULTS Bone mineral content increased in the ALT group (+16%) and decreased in the C group (-32%). Quadriceps muscle mass was lower in C (-27%) and CH (-19%) compared to ALT and ALTH. Myogenin mRNA expression was higher in C than ALT, ALTH and CH. Protein kinase B (Akt) mRNA expression was higher in both C and CH than ALT and ALTH. Mammalian target of rapamycin expression was higher in CH than ALT and ALTH. Muscle RING-finger protein-1 expression was higher in both C and CH than ALT and ALTH. CONCLUSION HMB intake improved bone properties and attenuated the depression of protein synthesis during a simulated sustained military operation.

Effects of Elastic Band Resistance Training on Glucose Control, Body Composition, and Physical Function in Women With Short- vs. Long-Duration Type-2 Diabetes.

Abstract Park, B-S, Khamoui, AV, Brown, LE, Kim, D-Y, Han, K-A, Min, K-W, and An, G-H. Effects of elastic band resistance training on glucose control, body composition, and physical function in women with short- vs. long-duration type-2 diabetes. J Strength Cond Res 30(6): 1688–1699, 2016—This study examined whether the existing duration of type-2 diabetes influenced patient responses to progressive resistance training. Twenty-six women with type-2 diabetes were stratified into short- (3 ± 2 years; n = 12) or long-standing (10 ± 3 years; n = 14) disease groups. Patients participated in a high daily or high weekly frequency elastic band resistance training program that consisted of 2 daily sessions, 5 d·wk−1 for 12 weeks. Glucose control, body composition, and physical function were evaluated pre- and posttraining. No significant diabetes duration × training interactions were detected for blood markers of glucose control (p > 0.05); however, there were significant main effects of training driven by comparable improvements in both cohorts (hemoglobin A1c, −13 to 18%; fasting glucose, −23 to 31%; postprandial glucose, −36 to 40%; insulin, −34 to 40%; C-peptide, −38 to 51%; p ⩽ 0.05). Anthropometrics and body composition were also favorably modified in both the groups after training (weight, −5 to 9%; body mass index, −6 to 9%; waist-to-hip ratio, −3 to 5%; percent fat, −14 to 20%; p ⩽ 0.05). Likewise, indices of physical function improved in both the groups after training (bicep curl repetitions, +15–33%; sit-and-stand repetitions, +45–47%; p ⩽ 0.05). A few exceptions were noted in which patients with long-standing disease demonstrated greater pre-to-post gains (p ⩽ 0.05) in grip strength (+11–13%) and peak exercise time (+19%) and load (+21%) during graded exercise, whereas those with shorter disease duration did not. Overall, these data suggest that patients with a long history of diabetes respond positively to resistance training and in a manner comparable to their recently diagnosed counterparts. Therefore, current inactivity in patients with long-standing disease should not deter from beginning an exercise program.

β-Hydroxy-β-Methylbutyrate as a Countermeasure for Cancer Cachexia: A Cellular and Molecular Rationale

Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass represents an important objective in the cancer patient trajectory not only because it relates to ones capacity to perform activities of daily living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard, research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches, administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by highlighting the cellular and molecular aspects of HMB function.