During aging, skeletal muscles show reduced mass and functional capacity largely due to loss of the regenerative ability of satellite cells (SCs), the quiescent stem cells located beneath the basal lamina surrounding each myofiber. While both the external environment and intrinsic properties of SCs appear to contribute to the age-related SC deficiency, the latter ones have been poorly investigated especially in humans. In the present work, we analyzed several parameters of SCs derived from biopsies of vastus lateralis muscle from healthy non-trained young (28.7 ± 5.9 years; n = 10) and aged (77.3 ± 6.4 years; n = 11) people. Compared with young SCs, aged SCs showed impaired differentiation when cultured in differentiation medium, and exhibited the following: (1) reduced proliferation; (2) higher expression levels of S100B, a negative regulator of myoblast differentiation; (3) undetectable levels in growth medium of full-length RAGE (receptor for advanced glycation end products), a multiligand receptor of the immunoglobulin superfamily, the engagement of which enhances myoblast differentiation; and (4) lower expression levels of the transcription factors, MyoD and Pax7. Also, either overexpression of full-length RAGE or knockdown of S100B in aged SCs resulted in enhanced differentiation, while overexpression of either a non-transducing mutant of RAGE (RAGE?cyto) or S100B in young SCs resulted in reduced differentiation compared with controls. Moreover, while aged SCs maintained the ability to respond to mitogenic factors (e.g., bFGF and S100B), they were no longer able to secrete these factors, unlike young SCs. These data support a role for intrinsic factors, besides the extracellular environment in the defective SC function in aged skeletal muscles.
Several studies have examined the effects of vibrations on muscle mass and performance in young healthy people. We studied the effects of vibrations on muscles of elderly male and female volunteers (65-85 years of age) diagnosed with sarcopenia. We applied mechanical vibrations locally (local vibrational training) to the thigh muscles at 300 Hz for a period of 12 weeks, starting with a session of 15 min stimulation once a week and increasing to three sessions of 15 min per week. Treated muscles displayed enhanced maximal isometric strength and increased content of fast MyHC-2X myosin. Single muscle fiber analysis did not show any change in cross-sectional area or in specific tension. Analysis of transcriptional profiles by microarray revealed changes in gene expression after 12 weeks of local vibrational training. In particular, pathways related with energy metabolism, sarcomeric protein balance and oxidative stress response were affected. We conclude that vibration treatment is effective in counteracting the loss of muscular strength associated with sarcopenia and the mode of action of vibration is based on cellular and molecular changes which do not include increase in fiber or muscle size.
Sarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage evidences. The aim of the present study was to determine the effects of aging on myoblasts and myotubes obtained from human skeletal muscle, and characterize the transcriptional profile as molecular expression patterns in relation to age-dependent modifications in their regenerative capacity. Our data show that the failure to differentiate does not depend on reduced myogenic cell number, but difficulty to complete the differentiation program. Data reported here suggested the following findings: (i) oxidative damage accumulation in molecular substrates, probably due to impaired antioxidant activity and insufficient repair capability, (ii) limited capability of elderly myoblasts to execute a complete differentiation program; restricted fusion, possibly due to altered cytoskeleton turnover and extracellular matrix degradation and (iii) activation of atrophy mechanism by activation of a specific FOXO-dependent program.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.