Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Abstract

ular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation. Experimental Gerontology, Elsevier, 2009, 44 (8) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT AbstractSarcopenia 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.

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

“…During development, some cells, including myoblasts, can migrate over large distances. Therefore, in the reorganisation that occurs during cell differentiation processes, adhesion molecules are involved [66]. We found Vcam1 and Ncam-180 up-regulated, both of which code for cell adhesion molecules and which contribute to myotube formation through fusion of myoblasts [39,40].…”

Impaired hypertrophy in myoblasts is improved with testosterone administration

“…Interestingly, similar morphology, transcript and signalling processes were also observed in cells isolated from aged human muscle [33][34][35] and in whole tissue biopsies [36,37]. Thus, these cells can be used as a representative model to investigate mechanisms of atrophic phenotypes (PD) vs. parental control cells (CON) that display hypertrophic phenotypes [7].…”

Primary human muscle precursor cells obtained from young and old donors produce similar proliferative, differentiation and senescent profiles in culture

“…Another concern is that some studies compare populations of MPCs that do not have equivalent proportions of cells expressing desmin (Beccafico et al, 2007;Pietrangelo et al, 2009). In human populations, desmin content reflects the proportion of CD56 positive, myogenic cells in the culture, with desmin negative cells being labelled by TE7 expression (Agley, Rowlerson, Velloso, Lazarus and Harridge, unpublished observations) and therefore determines differentiation potential of a cell population independently of age (Pietrangelo et al, 2009).…”