The Relationships of Age, Physical Activity Level, Adiposity, and Diet, with Human Satellite Myogenesis, and Metabolism
Fausnacht, Dane Weston
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In healthy individuals, satellite cells are partly responsible for muscle repair and preventing atrophy. Previous studies have linked the loss of muscle mass associated with aging to satellite cell dysfunction, postulating that satellite cell function diminishes with age. New evidence suggests that this may not be true as satellite cells collected from healthy aged participants appear indistinguishable from their healthy young counterparts. Satellite cell dysfunction appears to be more mechanistically linked to poor lifestyle factors such as low physical activity, improper diet, and increased adiposity. For this study, satellite cell function was evaluated against the effects of aging, diet, activity level, and adiposity. Satellite cells were collected from the vastus lateralis of sedentary (<2 hours/week activity) male donors categorized into young (18-30 years) and older (60-80 years) groups, as well as a young endurance trained group (18-30 years, 5+ hours/week of running/cycling). Cells were collected in young sedentary males before and after a four-week, high fat (55% of kcal), and hypercaloric (+1000 kcal over DEE) diet (HFHCD). Cells were also subjected to an in-vitro, high substrate media (HSM) challenge, then grown in media with a fivefold increase in glucose (25 mM) and an additional 400 uM of fatty acids (2:1 palmitate:oleate) before seven days of serum starved differentiation. The cells were evaluated for their proliferation rate, ability to differentiate (fusion index), rate of reactive oxygen species (ROS) production, and capacity for substrate oxidation (glucose and fatty acid). The young group exhibited a lower proportion of body fat than the older group (22.4%±8.1 vs. 28.3%±6.3). When compared to the older group, the young group also presented elevated oxidative efficiency (68%, p<0.05) and reduced pyruvate oxidation (-60%, p<0.05) in measures of muscle tissue homogenate. However, isolated satellite cells from the young and older group demonstrated no observable differences in any measures (proliferation rate, fusion index, ROS production, or substrate oxidation), other than increased oxidative efficiency in cells from older vs. younger donors. Cells from young endurance trained donors demonstrated faster proliferation rates (39%, p<0.05) and elevated early stage fusion (33%, p<0.05) when compared to cells from older individuals. Compared to pre-diet measures, cells collected post HFHCD revealed significantly reduced proliferation rates (-19%, p<0.05). When grown in HSM (as compared to control media), cells from young lean (<25% BF) and trained participants had blunted proliferation rates (-4.8% and -12.6%, p<0.05), fusion index scores (p<0.05), and ROS production rates. Cells collected from participants with higher adiposity (>25% BF) and those collected post HFHCD experienced increased proliferation and fusion when exposed to the HSM. This data suggests that donor activity level, adiposity, and diet but not age are mediating factors for satellite cell function. The cells appear to develop a preference for their in-vivo environment, as cells collected from the leaner and trained participants had their proliferation and fusion rates reduced when exposed to HSM. Conversely, exposure to the HSM accelerated the proliferation and fusion of cells collected from donors with higher body fat and those collected post HFHCD.
- Doctoral Dissertations