Presence of the vitamin D receptor and direct effects of vitamin D on the proliferation and differentiation of muscle precursor cells have been demonstrated in animal models. However, the effects and mechanisms of vitamin D actions in human skeletal muscle, and the presence of the vitamin D receptor in human adult skeletal muscle, remain to be established. Here, we investigated the role of vitamin D in human muscle cells at various stages of differentiation. We demonstrate that the components of the vitamin D-endocrine system are readily detected in human muscle precursor cells but are low to nondetectable in adult skeletal muscle and that human muscle cells lack the ability to convert the inactive vitamin D-metabolite 25-hydroxy-vitamin D3 to the active 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3). In addition, we show that 1α,25(OH)2D3 inhibits myoblast proliferation and differentiation by altering the expression of cell cycle regulators and myogenic regulatory factors, with associated changes in forkhead box O3 and Notch signaling pathways. The present data add novel information regarding the direct effects of vitamin D in human skeletal muscle and provide functional and mechanistic insight to the regulation of myoblast cell fate decisions by 1α,25(OH)2D3.

Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21–78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.

Maximal over-the-counter doses of ibuprofen attenuate strength and muscle hypertrophic adaptations to 8 weeks of resistance training in young adults. Thus, young individuals using resistance training to maximize muscle growth or strength should avoid excessive intake of anti-inflammatory drugs.

Tungsten microelectrodes were inserted percutaneously into the median nerve of alert human subjects for recording and stimulation of single nerve fibres. Impulses from mechanoreceptive units in the glabrous skin of the hand were recorded and single afferents were characterized with respect to unit type (FA I, FA II, SA I, and SA II), as well as size and shape of receptive field, and force threshold. The electrode was then reconnected to an electrical stimulator and short pulse trains (0.25 to 0.5 s, 20 to 100 Hz) were delivered at successively increasing current intensity, while the subject was asked to report any sensation that he noticed in the hand. The first sensation was always that of a localized skin deformation within a small area, typically 2 to 3 mm in diameter, often coinciding with the receptive field of the recorded unit. Spatial matching was also found in many cases for the size, shape and orientation of the perceptive and receptive fields, strongly suggesting that the sensation was accounted for by the recorded unit that had been selectively activated by the current pulses. There were clear differences between group data associated with the four types of units with regard to the quality of the percepts. Vibratory sensation was reported with all FA II units and was common with FA I units, whereas a sustained indentation was often associated with SA I units. Indirect evidence suggested that activation of SA II units usually did not elicit a sensation. It was confirmed that a single impulse in a single FA I unit may elicit a sensory response in the attending subject, whereas a much larger input was required from SA I units, which are also less sensitive to mechanical stimuli. This was one of several findings supporting the impression that differential receptive properties, even within a group of afferents, were associated with different sensory responses. It was concluded that a train of impulses in a single tactile unit may produce within the brain of the subject a construct which specifies with great accuracy the skin area of the unit's terminals as well as a tactile subquality which is related to unit properties.