Oxygen Consumption Rates Between Skeletal Muscle Cells Derived From Young and Old Human Donors Elucidate Mitochondrial Dysfunction

Abstract

Mitochondrial oxidative phosphorylation plays a significant role in cellular functions such as nutrient metabolism, ATP synthesis, and respiratory capacity. Mitochondria’s branching network, the reticulum, is active through the fusion (connection) and fission (fragmentation) dynamics. As humans age, however, there is a loss of mitochondrial fusion which increases fragmentation and this results in the loss of mitochondrial function. Therefore, the purpose of this study is to investigate mitochondrial dysfunction in human skeletal muscle derived cells (SkM). The discrepancies of the oxygen consumption rate (OCR) of the mitochondria between the young versus old human cells may reflect the driving factor behind aging. In order to determine mitochondrial dysfunction, OCR was measured between a primary human SkM from an 18 year‐old‐male (18M) and 66 year old male (66M) were purchased from Cook MyoSite Inc. (Pittsburgh, PA). OCR was measured using the Cell Mito Stress Test by SeaHorse Analytics XFp Analyzer (Agilent Technologies; Santa Clara, CA). Data generated by Seahorse Report Generator (Mean±SEM). Basal OCR and Maximal OCR were higher in 18M compared to 66M (Basal: 28.51 ± 1.61 and 20.43 ± 2.18; Maximal: 54.98 ± 6.74 and 28.68 ± 3.91 pmol/min). In addition, the results reflected that ATP production as well as Spare Respiratory Capacity (SRC) were higher in 18M compared to 66M (ATP Production: 23.88 ± 1.37 and 16.84 ± 2.04; SRC: 26.47 ± 5.13 and 8.25 ± 1.73 pmol/min). Basal OCR, Maximal OCR, ATP Production, and SRC of the 18M cells were higher than those of the 66M cells, revealing a greater mitochondrial function in the primary skeletal muscle‐derived cells derived from the young compared to the old. This could be accounted for by the fact that the young cells have a higher stress adaptability compared to the old cells. The discrepancies in the OCR between the young versus the old human cells, therefore, augment our understanding of how mitochondrial dysfunction may serve as a driving force behind aging in humans. Combining data from additional samples to be obtained, this study will elucidate the various mechanisms that propel age‐related mitochondrial dysfunction and provide crucial information to prevent skeletal muscle pathologies. Therefore, this project will unveil the effects of aging on skeletal muscle mitochondrial dysfunction and mitigate age‐related muscle pathologies.