No abstract

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.

To distinguish the respective potential of endurance and resistance training to increase the satellite cell pool, we investigated the effects of 14 weeks of concurrent lower body endurance and upper body resistance training (3 sessions/week) on vastus lateralis (VLat) and deltoid (Del) muscles of 10 active elderly men. NCAM+ satellite cells and myonuclear number were assessed in VLat and Del. After 14 weeks of training the NCAM+ satellite cell pool increased similarly (+38%) in both muscles, mainly in type II muscle fibers (P < 0.05). There was no significant change in myonuclear number or myonuclear domain in either muscle. Combining resistance training in the upper limbs with endurance training in the lower limbs is an efficient strategy to enhance the satellite cell pool in upper and lower body muscles in elderly subjects. Our results provide a practical reference for the determination of optimal exercise protocols to improve muscle function and regeneration in the elderly.

The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells improved when more fibers were included. Second, we report that small differences in counting satellite cells using CD56 and Pax7 antibodies can be attributed to the different staining profiles. Third, we provide support for the use of Ki67 in evaluating the proportion of active satellite cells. We observed very few (up to 1.3%) active satellite cells in healthy adult skeletal muscle at rest, but they increased significantly (up to 7-fold) following muscle activity. This study provides valuable tools to assess the behavior of satellite cells, both in pathological conditions and in response to physiological stimuli.

We investigated the effects of endurance training on satellite cells, which are a major component of the regenerative capacity of muscles. Muscle biopsies were obtained from the vastus lateralis of 11 men aged between 70 and 80 years who trained for 14 weeks (work load corresponding to 65-95% of peak oxygen consumption, VO(2) peak). Satellite cells were identified by immunohistochemistry. There was a significant increase in satellite cell number. Additionally, VO(2) peak, citrate synthase activity, and the area of type IIA fibers were significantly increased. Fiber type distribution and the myonuclear number were not significantly affected. The enhancement of satellite cell frequency and fiber area indicate that endurance training is an efficient strategy to improve muscle function in the elderly.

Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.

Muscle microvascularization is usually quantified in transverse sections, in absolute terms (capillaries around fibres, CAF, or capillary-to-fibre ratio, C/F) or as CAF related to fibre area (CAF/area, CAFA). The capillary-to-fibre perimeter exchange ratio (CFPE) has been introduced in order to assess the role of the capillary-to-fibre interface in resistance to O 2 diffusion. The ratio between the length of capillaries in contact with fibres and fibre perimeter (LC/PF) has also been used as an index for capillary tortuosity. The possibility of change in capillary tortuosity with endurance training was not considered in previous studies. Consequently, this study investigated the effect of 14 weeks of endurance training on muscle microvascularization, including microvessel tortuosity, in 11 elderly men (8th decade). Microvessels were analysed using the CD31 antibody. Together with the significant increase in peak oxygen exchange and citrate synthase activity, there was a significant increase in C/F. While CFPE and CAFA remained unchanged, an important finding was the clear increase in LC/PF (56%; P < 0.001) for a same sarcomere length. We also found a strong correlation between oxidative enzyme activity and LC/PF both before and after training. These results indicate that endurance training induces significant remodelling in the microvessel network in elderly men and that an increase in the degree of microvessel tortuosity would be an important mechanism of adaptation to endurance training.

The aim of this investigation was to study the distribution of satellite cells in slow (type I fibres) and fast (type II fibres) fibres from human vastus lateralis muscle. This muscle is characterised by a mixed fibre type composition and is considered as the site of choice for biopsies in research work and for clinical diagnosis. Biopsy samples were obtained from five healthy young volunteers and a total of 1,747 type I fibres and 1,760 type II fibres were assessed. Satellite cells and fibre type composition were studied on serial muscle cross-sections stained with specific monoclonal antibodies. From a total of 218 satellite cells, 116 satellite cells were found in contact with type I fibres (53.6+/-8% of the satellite cells associated to type I fibres) and 102 satellite cells in contact with type II fibres (46.4+/-8% of the satellite cells associated to type II fibres). There was no significant difference (P=0.4) between the percentages of satellite cells in contact with type I and with type II fibres. Additionally, there was no relationship between the mean number of satellite cells per fibre and the mean cross-sectional area of muscle fibres. In conclusion, our results show that there is no fibre type-specific distribution of satellite cells in a human skeletal muscle with mixed fibre type composition.