Abstract
Aging of population brings related social problems, such as muscle attenuation and regeneration barriers with increased aging. Muscle repair and regeneration depend on muscle stem cells (MuSCs). Obstructive sleep apnea (OSA) rises in the aging population. OSA leads to hypoxia and upper airway muscle injury. However, little is known about the effect of increasing age and hypoxia to the upper airway muscle. The genioglossus (GG) is the major dilator muscle to keep the upper airway open. Here, we reported that muscle fiber and MuSC function declined with aging in GG. Increasing age also decreased the migration and proliferation of GG MuSCs. p53 and p21 were high expressions both in muscle tissue and in GG MuSCs. We further found that hypoxia inhibited GG MuSC proliferation and decreased myogenic differentiation. Then, hypoxia enhanced the inhibition effect of aging to proliferation and differentiation. Finally, we investigated that hypoxia and aging interact to form a vicious circle with upregulation of p53 and p21. This vicious hypoxia plus aging damage accelerated upper airway muscle injury. Aging and hypoxia are the major damage elements in OSA patients, and we propose that the damage mechanism of hypoxia and aging in GG MuSCs will help to improve upper airway muscle regeneration.
Highlights
The root source of obstructive sleep apnea (OSA) is repeated hypoxia during sleep [1, 2], and OSA has a higher prevalence at advanced age [3, 4]
To investigate whether GG muscle was altered by increasing age, we first examined the cross-sectional area (CSA) of muscle fibers which derived from four age groups
Our results suggested that hypoxia and aging interact to form a vicious circle with upregulation of p53 and p21, and this vicious hypoxia plus aging damage accelerated upper airway muscle injury
Summary
The root source of obstructive sleep apnea (OSA) is repeated hypoxia during sleep [1, 2], and OSA has a higher prevalence at advanced age [3, 4]. The effect of increasing age to GG function and the related mechanism remains to be elucidated. Muscle stem cells (MuSCs) are responsible for muscle growth and injury repair throughout the life [8]. MuSCs can differentiate into myocytes and fuse with each other to repair damaged muscle [9, 10]. Muscle is a homeostatic tissue and can tolerate daily wear-and-tear by repair and regeneration [11]. The important reason of progressive weaken and regenerative dysfunction is the functional decline muscle MuSCs [12]. There are inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis [13]. GG repair and regeneration are very important to OSA patients. The influence of aging to GG MuSCs is still unknown
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