Dataset Information

Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury.

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.

SUBMITTER: Zhu LY

PROVIDER: S-EPMC7073476 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury.

Zhu Lu-Ying LY Yu Li-Ming LM Zhang Wei-Hua WH Deng Jia-Jia JJ Liu Shang-Feng SF Huang Wei W Zhang Meng-Han MH Lu Yan-Qin YQ Han Xin-Xin XX Liu Yue-Hua YH

Stem cells international 20200304

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 r ...[more]

PMID: 32190060

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Project description:Single motor unit (SMU) analysis provides a means to examine the motor control of a muscle. SMUs in the genioglossus show considerable complexity, with several different firing patterns. Two of the primary stimuli that contribute to genioglossal activation are carbon dioxide (CO(2)) and negative pressure, which act through chemoreceptor and mechanoreceptor activation, respectively. We sought to determine how these stimuli affect the behavior of genioglossus SMUs. We quantified genioglossus SMU discharge activity during periods of quiet breathing, elevated CO(2) (facilitation), and continuous positive airway pressure (CPAP) administration (inhibition). CPAP was applied in 2-cmH(2)O increments until 10 cmH(2)O during hypercapnia. Five hundred ninety-one periods (each ? 3 breaths) of genioglossus SMU data were recorded using wire electrodes(n = 96 units) from 15 awake, supine subjects. Overall hypercapnic stimulation increased the discharge rate of genioglossus units (20.9 ± 1.0 vs. 22.7 ± 0.9 Hz). Inspiratory units were activated ? 13% earlier in the inspiratory cycle, and the units fired for a longer duration (80.6 ± 5.1 vs. 105.3 ± 4.2% inspiratory time; P < 0.05). Compared with baseline, an additional 32% of distinguishable SMUs within the selective electrode recording area were recruited with hypercapnia. CPAP led to progressive SMU inhibition; at ? 6 cmH(2)O, there were similar numbers of SMUs active compared with baseline, with peak frequencies of inspiratory units close to baseline, despite elevated CO(2) levels. At 10 cmH(2)O, the number of units was 36% less than baseline. Genioglossus inspiratory phasic SMUs respond to hypercapnic stimulation with changes in recruitment and rate coding. The SMUs respond to CPAP with derecruitment as a homogeneous population, and inspiratory phasic units show slower discharge rates. Understanding upper airway muscle recruitment/derecruitment may yield therapeutic targets for maintenance of pharyngeal patency.

Dataset Information

Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury.

Publications

Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury.

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