Hans Degens

The role of systemic inflammation in age‐related muscle weakness and wasting

Ageing is associated with a slow, but progressive muscle weakness, which is largely attributable to muscle wasting. A diminished function of satellite cells at old age may hamper preservation and repair from (contraction)‐induced injury and contribute to the age‐related muscle wasting. Satellite cell function may be affected by circulating factors, as muscle regeneration in old mice sharing the circulation of young mice is not impaired. Chronic low‐grade systemic inflammation in old organisms may be that environmental factor. Indeed, the inflammatory cytokine tumor necrosis factor‐α (TNFα) negatively affects the muscle regenerating capacity. TNFα destabilizes MyoD, a muscle‐specific transcription factor involved in satellite cell proliferation and differentiation, and induces apoptosis of satellite cells, particularly at old age. Here it is proposed that some of these effects are mediated by TNFα‐induced expression of inhibitors of differentiation proteins. Yet, the increase in TNFα during the normal inflammatory response helps, rather than impairs, the repair process. This apparent contradiction may be resolved by the fact that the effects of TNFα are concentration and time dependent. Thus, the negative effect of systemic inflammation on muscle strength at old age may only become apparent when it exceeds a certain threshold and persists for a prolonged period.

Skeletal muscle function and hypertrophy are diminished in old age

Muscle loss occurs during aging. To investigate whether the hypertrophic response is attenuated at old age, we used male Fischer 344 (26 months old; n = 5) and Fischer 344 x Brown Norway rats (6, 9, and 33 months old; n = 8, 10, and 6, respectively). Hypertrophy of the left plantaris muscle was induced by surgical denervation of its agonists. The right leg served as control. The mass and maximal tetanic force (P0) of control muscles declined by ∼30% between 9 and 26 months (P < 0.05). Fatigue resistance during intermittent isometric contractions was reduced by ∼60% at 33 months. At 33 months, the attenuated hypertrophy was accompanied by a decrease rather than an increase in P0. Yet, hypertrophy was accompanied by a 25% rise in fatigue resistance at all ages (P = 0.001). Thus, aging is associated with a decline in muscle mass and function. In addition, at advanced age, the hypertrophic response is reduced and a hypertrophic stimulus even aggravates the age‐associated muscle weakening. Muscle Nerve 27: 339–347, 2003

Sex differences in contractile properties and fatigue resistance of human skeletal muscle

To explore the cause of higher skeletal muscle fatigue resistance in women than men, we used electrically evoked contractions (1 s on, 1 s off, 30 Hz, 2 min), which circumvent motivational bias and allow examination of contractile properties. We compared 29 men [26.5 (7.0) years old; mean (s.d.)] with 35 women [25.4 (7.6) years old]. Strength of the quadriceps muscle was higher in men than women (P < 0.001). The lower maximal rate of relaxation in women (P= 0.002) indicates that their muscles were slower than those of men. The torque declined less in women than in men [37.7 (10.7) versus 29.9 (10.0)%; P= 0.002], and was not related to muscle strength or size, as determined with magnetic resonance imaging. The sex difference in fatigability was also seen when the circulation to the leg was occluded [torque declined 76.9 (10.8) versus 59.5 (16.9)% in men versus women, respectively; P= 0.008]. The maximal rate of relaxation correlated with the fatigability of the muscle under all conditions (correlations ranging from 0.34 to 0.51, P < 0.02). We conclude that the sex‐related difference in skeletal muscle fatigue resistance is not explicable by differences in motivation, muscle size, oxidative capacity and/or blood flow between sexes, but might be related to differences in fibre type composition.

The acute effect of different warm-up protocols on anaerobic performance in elite youth soccer players.

Needham, RA, Morse, CI, and Degens, H. The acute effect of different warm-up protocols on anaerobic performance in elite youth soccer players. J Strength Cond Res 23(9): 2614-2620, 2009-The purpose of the study was to investigate the acute effect of different warm-up protocols on anaerobic performance in elite youth soccer players. Twenty elite youth soccer players (mean age 17.2 ± 1.2 years) performed 3 different warm-up protocols in a random order on nonconsecutive days. Each warm-up protocol consisted of a 5-minute low-intensity jog followed by 10 minutes of static stretching (SS), dynamic stretching (DS), or dynamic stretching followed by 8 front squats + 20% body mass (DSR). Subjects performed a countermovement jump followed by a 10- and 20-m sprint test immediately and at 3 and 6 minutes after each warm-up protocol. Vertical jump performance following DSR was better at 3 and 6 minutes than after DS, which in turn was better than after SS at 0, 3, and 6 minutes (p < 0.05). Jump performance was better at 3 minutes than immediately after, and this improvement was maintained at 6 minutes after DSR (p < 0.05). A better sprint performance was observed after DSR and DS compared with SS immediately and at 3 and 6 minutes following each warm-up protocol (p < 0.05). The results of the study suggest that a dynamic warm-up with the inclusion of resistance enhances jumping ability more than dynamic exercise alone. In addition, a dynamic warm-up produces a superior sprint and jump performance compared to a warm-up consisting of static stretching.

Determination of oxygen consumption in muscle during exercise using near infrared spectroscopy.

The aim of this study was to determine oxygen consumption (VO2) during isometric exercise in human muscles using near infrared spectroscopy (NIRS). The technique was used to study the relationship between VO2 in the soleus muscle and the level of isometric exercise expressed as percentages of the maximum voluntary contraction (MVC). For the study 11 healthy male volunteers were recruited. Reproducibility was studied in 6 subjects. The subjects were seated in a chair with the knee joint at an angle of 90°. The optodes of the NIRS instrument were attached to the lateral aspect of the soleus muscle. A horizontal bar above the knee was connected to a dynamometer. Subjects applied isometric force to the bar by producing a torque at the ankle joint. Firstly the MVC was determined. Secondly the VO2 at rest and at 5 levels of isometric exercise, ranging from 5% to 25% of MVC and increasing by 5% each stage, was measured. In all cases the VO2 at rest or during isometric contraction was determined from the decrease of the oxyhaemoglobin (O2Hb) signal immediately after arterial occlusion of the thigh. Repeated measurements showed no significant difference between trials, indicating that the measurements were reproducible. At rest a VO2 of 6.7 ± 1.1 μMO2Hb min‐1 (mean ± S.E.M.) was found, a result comparable with other studies. In all subjects a linear relationship was found between the VO2 and the level of exercise. The average slope of the regression lines of all individuals was 0.85 ± 0.22 μuMO, Hb min‐1 MVC‐1 (mean ± S.E.M.). Inter‐individual variation of the slopes was high and ranged from 0.28 to 2.29 μuMO2 Hb‐ min‐1 %MVC‐1, which can be explained by differences in fat percentage and in the measuring volume of the NIRS instrument. NIRS appeared to be a reproducible and reliable method for the non‐invasive measurement of VO2 in human muscles. The method could be used to investigate regional differences as well as changes in time between muscle groups as a function of training.

Age-Related Changes in the Microcirculation of Skeletal Muscle

The age-related reduction in exercise capacity is associated with a reduction in cardiac output and maximal oxygen consumption (VO2max). The loss of muscle mass explains a large portion of the age-related decline in VO2max. The capillary supply to a muscle fibre is primarily determined by its size, but also by its metabolic profile and the metabolic profile of surrounding fibres. Thus the age-related fibre atrophy and changes in the fibre type composition are expected to be accompanied by changes in the capillarisation. The exchange of oxygen, blood-borne energy sources, metabolites and heat between the blood and muscle tissue takes place in the microcirculation. Changes in the microcirculation may thus affect the functioning and viability of the muscle. The resting blood flow is minimally affected by age, but blood flow during or following exercise is generally reduced. This may in part be due to a reduced vasodilatory capacity and a decreased capillarisation. However, the coupling between capillary supply to a fibre and its metabolic profile or the profile of the surrounding fibres is maintained. There are some changes in ultrastructure of the endothelium. The age-related changes in the microcirculation are associated with a reduced VO2max and exercise capacity. The adaptability of the microcirculation is maintained at old age.

Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart

Abstract Cardiac hypertrophy and failure are associated with alterations in cardiac substrate metabolism. It remains to be established, however, whether genomically driven changes in cardiac glucose and fatty acid (FA) metabolism represent a key event of the hypertrophic remodeling process. Accordingly, we investigated metabolic gene expression and substrate metabolism during compensatory hypertrophy, in relation to other cardiac remodeling processes.Thereto, cardiac hypertrophy was induced in rats by supra–renal aortic constriction to various degrees, resulting in increased heart/body weight ratios of 22% (Aob–1), 24% (Aob–2) and 32% (Aob–3) (p < 0.005) after 4 weeks. The unaltered ejection fraction in all groups indicated that the hypertrophy was still compensatory in nature. β–Myosin Heavy Chain protein and ANF mRNA levels were increased in all groups. Only in Aob–3 rats were SERCA2a mRNA levels markedly reduced. In this group, glycolytic capacity was modestly elevated (+ 25%; p < 0.01). Notwithstanding these phenotypical changes, the expression of genes involved in FA metabolism and FA oxidation rate in cardiac homogenates was completely preserved, irrespective of the degree of hypertrophy. These findings indicate that cardiac FA oxidative capacity is preserved during compensatory hypertrophy, and that a decline in metabolic gene expression does not represent a hallmark of the development of hypertrophy.

Noninvasive Estimation of Myosin Heavy Chain Composition in Human Skeletal Muscle

PURPOSE Information on muscle fiber type composition is of great importance in muscle physiology and athletic performance. Because there are only a few techniques available that noninvasively and accurately provide an estimate of muscle fiber type composition, the development of additional and alternative approaches is required. METHODS Twenty-seven participants (21 men, 6 women) with an average age of 43 ± 18 yr, height of 175 ± 7 cm, and mass of 74 ± 12 kg participated in the study. Delay, contraction, and half relaxation times were calculated from tensiomyographic radial twitch responses of the vastus lateralis muscle. Univariate and multiple linear regression analyses were used to correlate the proportion of myosin heavy chain I (%MHC-I) in a biopsy obtained from the same muscle with a single and all three radial twitch parameters. RESULTS Delay, contraction, and half relaxation times all correlated with %MHC-I (r = 0.612, 0.878, and 0.669, respectively, at P ≤ 0.001). When all three parameters were included in a multiple linear regression, the correlation with the %MHC-I was even better (R = 0.933, P < 0.001). CONCLUSIONS These data suggest that time parameters of the skeletal muscle mechanical radial twitch response, measured with a contact linear displacement sensor, can be used as an accurate noninvasive predictor of the %MHC-I in a muscle.

Physical activity in older age: perspectives for healthy ageing and frailty

Regular physical activity helps to improve physical and mental functions as well as reverse some effects of chronic disease to keep older people mobile and independent. Despite the highly publicised benefits of physical activity, the overwhelming majority of older people in the United Kingdom do not meet the minimum physical activity levels needed to maintain health. The sedentary lifestyles that predominate in older age results in premature onset of ill health, disease and frailty. Local authorities have a responsibility to promote physical activity amongst older people, but knowing how to stimulate regular activity at the population-level is challenging. The physiological rationale for physical activity, risks of adverse events, societal and psychological factors are discussed with a view to inform public health initiatives for the relatively healthy older person as well as those with physical frailty. The evidence shows that regular physical activity is safe for healthy and for frail older people and the risks of developing major cardiovascular and metabolic diseases, obesity, falls, cognitive impairments, osteoporosis and muscular weakness are decreased by regularly completing activities ranging from low intensity walking through to more vigorous sports and resistance exercises. Yet, participation in physical activities remains low amongst older adults, particularly those living in less affluent areas. Older people may be encouraged to increase their activities if influenced by clinicians, family or friends, keeping costs low and enjoyment high, facilitating group-based activities and raising self-efficacy for exercise.

Aging related changes in determinants of muscle force generating capacity: A comparison of muscle aging in men and male rodents

Human aging is associated with a progressive decline in skeletal muscle mass and force generating capacity, however the exact mechanisms underlying these changes are not fully understood. Rodents models have often been used to enhance our understanding of mechanisms of age-related changes in human skeletal muscle. However, to what extent age-related alterations in determinants of muscle force generating capacity observed in rodents resemble those in humans has not been considered thoroughly. This review compares the effect of aging on muscle force generating determinants (muscle mass, fiber size, fiber number, fiber type distribution and muscle specific tension), in men and male rodents at similar relative age. It appears that muscle aging in male F344*BN rat resembles that in men most; 32-35-month-old rats exhibit similar signs of muscle weakness to those of 70-80-yr-old men, and the decline in 36-38-month-old rats is similar to that in men aged over 80 yrs. For male C57BL/6 mice, age-related decline in muscle force generating capacity seems to occur only at higher relative age than in men. We conclude that the effects on determinants of muscle force differ between species as well as within species, but qualitatively show the same pattern as that observed in men.