David A. Jones

Physiological and functional evaluation of healthy young and older men and women: design of the European MyoAge study

Within the European multi-centre MyoAge project, one workpackage was designed to investigate the contribution of age-related changes to muscle mass, contractile characteristics and neural control in relation to reductions in mobility in older age. The methodology has been described here. Test centres were located in Manchester, UK; Paris, France; Leiden, The Netherlands; Tartu, Estonia and Jyväskylä, Finland. In total, 182 young (18–30xa0years old, 52.2xa0% female) and 322 older adults (69–81xa0years old, 50xa0% female) have been examined. The participants were independent living, socially active and free from disease that impaired mobility levels. The older participants were selected based on physical activity levels, such that half exceeded current recommended physical activity levels and the other half had lower physical activity levels than is recommended to maintain health. Measurements consisted of blood pressure; anthropometry and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging); lung function; standing balance and cognitive function (CANTAB). Mobility was assessed using the Timed Up and Go, a 6xa0min walk, activity questionnaires and accelerometers to monitor habitual daily activities. Muscle strength, power, fatigue and neural activation were assessed using a combination of voluntary and electrically stimulated contractions. Fasting blood samples and skeletal muscle biopsies were collected for detailed examination of cell and molecular differences between young and older individuals. The results from this study will provide a detailed insight into “normal, healthy” ageing, linking whole-body function to the structure and function of the neuromuscular system and the molecular characteristics of skeletal muscle.

Inter-individual variability in the adaptation of human muscle specific tension to progressive resistance training

Considerable variation exists between people in the muscle response to resistance training, but there are numerous ways muscle might adapt to overload that might explain this variable response. Therefore, the aim of this study was to quantify the range of responses concerning the training-induced change in maximum voluntary contraction (MVC) knee joint torque, quadriceps femoris (QF) maximum muscle force (F), physiological cross-sectional area (PCSA) and specific tension (F/PCSA). It was hypothesized that the variable change in QF specific tension between individuals would be less than that of MVC. Fifty-three untrained young men performed progressive leg-extension training three times a week for 9xa0weeks. F was determined from MVC torque, voluntary muscle activation level, antagonist muscle co-activation and patellar tendon moment arm. QF specific tension was established by dividing F by QF PCSA, which was calculated from the ratio of QF muscle volume to muscle fascicle length. MVC torque increased by 26xa0±xa011% (Pxa0<xa00.0001; range −1 to 52%), while F increased by 22xa0±xa011% (Pxa0<xa00.0001; range −1 to 44%). PCSA increased by 6xa0±xa04% (Pxa0<xa00.001; range −3 to 18%) and specific tension increased by 17xa0±xa011% (Pxa0<xa00.0001; range −5 to 39%). In conclusion, training-induced changes in F and PCSA varied substantially between individuals, giving rise to greater inter-individual variability in the specific tension response compared to that of MVC. Furthermore, it appears that the change in specific tension is responsible for the variable change in MVC.

Variation in the determinants of power of chemically skinned human muscle fibres

We have explored the extent to which the maximal velocity of unloaded shortening (Vmax), the force generated per unit cross‐sectional area (P0) and the curvature of the force–velocity relationship (a/P0 in the Hill equation) contribute to differences in peak power of chemically skinned single fibres from the quadriceps muscle of healthy young male subjects. The analysis was restricted to type I and IIA fibres that contained a single type of myosin heavy chain on electrophoretic separation. Force–velocity relationships were determined from isotonic contractions of maximally activated fibres at 15°C. Mean (±s.d.) peak powers were 1.99 ± 0.72 watts per litre (W L−1) for type I fibres and 6.92 ± 2.41 W L−1, for type IIA fibres. The most notable feature, however, was the very large, sevenfold, range of power outputs within a single fibre type. This wide range was a consequence of variations in each of the three components determining power: P0, Vmax and a/P0. Within a single fibre type, P0 varied threefold, and Vmax and a/P0 two‐ to threefold. There were no obvious relationships between P0 and Vmax or between P0 and a/P0. However, there was a suggestion of an inverse relationship between a/P0 and Vmax, the effect being to reduce, somewhat, the impact of differences in Vmax on peak power. In searching for the causes of variation in peak power of fibres of the same type, it appears likely that there are two factors, one that affects P0 and another that leads to variation in both Vmax and a/P0.

Age‐related neuromuscular changes affecting human vastus lateralis

Skeletal muscle size and strength decline in older age. The vastus lateralis, a large thigh muscle, undergoes extensive neuromuscular remodelling in healthy ageing, as characterized by a loss of motor neurons, enlargement of surviving motor units and instability of neuromuscular junction transmission. The loss of motor axons and changes to motor unit potential transmission precede a clinically‐relevant loss of muscle mass and function.

Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18–30xa0years and 260 subjects aged 69–81xa0years) recruited within the framework of the European research network project “Myoage”. The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.

Diagnostic measures for sarcopenia and bone mineral density.

SummaryCurrently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia.IntroductionDiagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome.MethodsIn the European cross-sectional study MYOAGE, 178 young (18–30xa0years) and 274 healthy old participants (69–81xa0years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height2), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models.ResultsLean mass and ALM/height2 were positively associated with BMD (Pu2009<u20090.001). Significance remained in all sex and age subgroups after further adjustment for fat mass, except in old women. Lean mass percentage and ALM percentage were inversely associated with BMD in old women (Pu2009<u20090.001). These inverse associations disappeared after adjustment for body mass. Knee extension torque and handgrip strength were positively associated with BMD in all subgroups (Pu2009<u20090.01), except in old women. Walking speed and TUG were not related to BMD.ConclusionsThe associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Diagnostic criteria for sarcopenia and physical performance

Relative and absolute muscle mass and muscle strength are used as diagnostic criteria for sarcopenia. We aimed to assess which diagnostic criteria are most associated with physical performance in 180 young (18–30xa0years) and 281 healthy old participants (69–81xa0years) of the European study MYOAGE. Diagnostic criteria included relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height squared and total lean mass), knee extension torque, and handgrip strength. Physical performance comprised walking speed, Timed Up and Go test (TUG), and in a subgroup physical fitness. Diagnostic criteria for sarcopenia and physical performance were standardized, and the associations were analyzed using linear regression models stratified by age category, with adjustments for age, gender, and country. In old participants, relative muscle mass was associated with faster walking speed, faster TUG, and higher physical fitness (all pu2009<u20090.001). Absolute muscle mass was not associated with physical performance. Knee extension torque and handgrip strength were associated with faster walking speed (both pu2009≤u20090.003). Knee extension torque was associated with TUG (pu2009=u20090.001). Knee extension torque and handgrip strength were not associated with physical fitness. In young participants, there were no significant associations between diagnostic criteria for sarcopenia and physical performance, except for a positive association between relative muscle mass and physical fitness (pu2009<u20090.001). Relative muscle mass, defined as lean mass or ALM percentage, was most associated with physical performance. Absolute muscle mass including ALM/height squared was not associated with physical performance. This should be accounted for when defining sarcopenia.

Age-dependent motor unit remodelling in human limb muscles

Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40xa0% fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50xa0% and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements.

Thigh muscle volume in relation to age, sex and femur volume.

Secular changes and intra-individual differences in body shape and size can confound cross-sectional studies of muscle ageing. Normalising muscle mass to height squared is often suggested as a solution for this. We hypothesised that normalisation of muscle volume to femur volume may be a better way of determining the extent of muscle lost with ageing (sarcopenia). Thigh and femur muscle volumes were measured from serial magnetic resonance imaging sections in 20 recreationally active young men (mean age 22.4xa0years), 25 older men (72.3xa0years), 18 young women (22.1xa0years) and 28 older women (72.0xa0years). There were no age-related differences in femur volume. The relationship between thigh muscle volume and femur volume (R2u2009=u20090.76; exponent of 1.12; Pu2009<u20090.01) was stronger than that with height (R2u2009=u20090.49; exponent of 3.86; Pu2009<u20090.01) in young participants. For young subjects, the mean muscle/bone ratios were 16.0 and 14.6 for men and women, respectively. For older men and women, the mean ratios were 11.6 and 11.5, respectively. The Z score for the thigh muscle/bone volume ratio relative to young subjects was −2.2u2009±u20090.7 for older men and −1.4u2009±u20090.8 for older women. The extent of sarcopenia judged by the muscle/bone ratio was approximately twice that determined when normalising to height squared. These data suggest that the muscle/bone ratio captures the intra-individual loss of muscle mass during ageing, and that the age-related loss of muscle mass may be underestimated when normalised to height squared. The quadriceps seems relatively more affected by ageing than other thigh muscles.

Skeletal muscle adaptations to physical inactivity and subsequent retraining in young men

Skeletal muscle structure and function are markedly affected by chronic disuse. With unloading, muscle mass is lost at rate of about 0.4xa0%/day but little is known about the recovery of muscle mass and strength following disuse. Here we report an extensive data set describing in detail skeletal muscle adaptations in structure and function in response to both disuse and retraining. Eight young men (23xa0±xa02.2xa0years) underwent 3xa0weeks of unilateral lower limb suspension (ULLS) followed by a 3-week resistance training recovery program. Knee extensor isometric torque, voluntary activation, quadriceps femoris (QF) muscle volume (QFvol), fascicle length (Lf) and pennation angle (θ), physiological cross-sectional area (PCSA) of all four heads of the QF muscle, were measured before, after ULLS, and post-ULLS-resistance training. Needle biopsies were taken from the vastus lateralis muscle of a subgroup (nxa0=xa06) of the same subjects and cross sectional area of individual muscle s and myosin content of muscle samples were determined. Following 3xa0weeks of ULLS, isometric torque decreased by 26xa0%, PCSA by 3xa0%, QFvol by 10xa0%. Lf and θ of all four heads of QF significantly decreased (pxa0≤xa00.05). Following the 3-week retraining period, isometric torque, PCSA, QFvol, Lf and θ of all four heads of QF were all fully restored to pre ULLS values. CSA of individual muscle fibres and myosin content of muscle samples decreased by 26 and 35xa0% respectively (post-ULLS) and recovered to almost pre-ULLS values following retraining. There were no significant changes in voluntary activation of the quadriceps muscles in response to either ULLS or subsequent retraining. These results indicate that: (1) the loss of muscle force with 3-week unloading in humans is mostly explained by muscle atrophy and by a decrease in myosin content and, (2) all the neuromuscular changes induced by this model of disuse can be fully restored after a resistance training intervention of equal duration.