The aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low... Show moreThe aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low muscle strength, while high acute pro-inflammatory response is associated with high muscle strength. Show less
ABSTRACT: INTRODUCTION: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim... Show moreABSTRACT: INTRODUCTION: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. METHODS: As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation. RESULTS: After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group. CONCLUSIONS: In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. Show less
Background: There is growing recognition of the serious consequences of sarcopenia on the functionality and autonomy in old age. Recently, the age-related changes in several inflammatory mediators... Show moreBackground: There is growing recognition of the serious consequences of sarcopenia on the functionality and autonomy in old age. Recently, the age-related changes in several inflammatory mediators have been implicated in the pathogenesis of sarcopenia. The purposes of this systematic review were two-fold: (1) to describe the patterns of muscle strength loss with age in the general population, and (2) to quantify the loss of muscle strength in rheumatoid arthritis as representative for an underlying inflammatory state. Handgrip strength was used as a proxy for overall muscle strength. Results: Results from 114 studies (involving 90,520 subjects) and 71 studies (involving 10,529 subjects) were combined in a meta-analysis for the general and rheumatoid arthritis population respectively and standardized at an equal sex distribution. For the general population we showed that between the ages of 25 years and 95 years mean handgrip strength declined from 45.5 kg to 23.2 kg for males and from 27.1 kg to 12.8 kg for females. We noted a steeper handgrip strength decline after 50 years of age (rate of 0.37 kg/year). In the rheumatoid arthritis population handgrip strength was not associated with chronological age between the ages of 35 years and 65 years and was as low as 20.2 kg in male and 15.1 in female. Rheumatoid arthritis disease duration was inversely associated with handgrip strength. Conclusions: This meta-analysis shows distinct patterns of age-related decrease of handgrip strength in the general population. Handgrip strength is strongly associated with the presence and duration of an inflammatory state as rheumatoid arthritis. The putative link between age-related inflammation and sarcopenia mandates further study as it represents a potential target for intervention to maintain functional independence in old age. (C) 2010 Elsevier B.V. All rights reserved. Show less
