GABA Prevents Sarcopenia by Regulation of Muscle Protein Degradation and Inflammaging in 23‐ to 25‐Month‐Old Female Mice

IF 8.9 1区 医学
Gunju Song, Hyun‐Ji Oh, Heegu Jin, Hyein Han, Boo‐Yong Lee
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引用次数: 0

Abstract

BackgroundSarcopenia is the gradual decrease in skeletal muscle mass, strength and function in elderly individuals. Gamma‐aminobutyric acid (GABA) is a neurotransmitter naturally produced from glutamate by the enzyme glutamic acid decarboxylase. Age‐related decline in GABA is linked to age‐related motor and sensory decline and seems to affect sarcopenia, yet no detailed study has been conducted. In this study, we aimed to investigate the effect of GABA on improving sarcopenia by suppressing muscle protein degradation through supplementing decreased GABA in old mice.MethodsGABA (10 or 30 mg/kg/day) was orally administered daily to young (3 months) and old (21–23 months) C57BL/6 mice for 7 weeks. The body weight and grip strength of the mice were measured weekly at the same time. After sacrificing the mice, the quadriceps and gastrocnemius muscles were excised from their hind limbs, and the spleen and serum were collected. Histological, biochemical and molecular analyses were conducted in various experiments.ResultsThe administration of GABA increased muscle strength (+41%, +70% compared to the aged mouse control group, GABA at doses of 10 or 30 mg/kg/day respectively, p < 0.05) and muscle mass (quadriceps: +28%, +46%; gastrocnemius: +12%, +19%, p < 0.05) in old mice. This increase was accompanied by a cross‐sectional area (CSA) increase in the quadriceps and gastrocnemius muscle (p < 0.05). The administration of GABA increased IGF‐1 levels in serum (p < 0.05), leading to the activation of muscle protein synthesis. We found that GABA inhibits sarcopenia by regulating muscle protein degradation through the activation of Akt/mTOR/FoxO3a signalling pathways. GABA also regulates inflammaging, which is a hallmark of age‐related muscle atrophy. There was a significant increase in the F4/80 + CD11b + total macrophage ratio in gastrocnemius and spleen, especially the M1 macrophage ratio increased in old mice. However, GABA administration was effective in suppressing M1 macrophages (gastrocnemius: −40%, − 53%; spleen: −22%, −26%, p < 0.05). Pro‐inflammatory cytokines such as TNF‐α and IL‐6, primarily secreted by M1 macrophages, are also decreased by treatment with GABA (TNF‐α: −24%, −27%; IL‐6: −45%, −59%, p < 0.05).ConclusionsTogether, this study demonstrates the importance of GABA in maintaining muscle and low‐chronic inflammation during ageing. We suggest that GABA shows potential as a substance that can effectively address sarcopenia and enhance the overall lifespan and well‐being of older individuals.
GABA 可通过调节 23 至 25 个月大雌性小鼠的肌肉蛋白降解和炎症反应预防肌肉疏松症
背景疏松症是指老年人的骨骼肌质量、力量和功能逐渐下降。γ-氨基丁酸(GABA)是一种神经递质,由谷氨酸脱羧酶从谷氨酸中自然生成。与年龄相关的 GABA 下降与与年龄相关的运动和感觉衰退有关,并且似乎会影响到肌肉疏松症,但目前还没有进行过详细的研究。本研究旨在探讨 GABA 通过补充老年小鼠体内减少的 GABA 来抑制肌肉蛋白质降解,从而改善肌肉疏松症的效果。同时每周测量小鼠的体重和握力。将小鼠处死后,切除其后肢股四头肌和腓肠肌,收集脾脏和血清。结果服用 GABA 可增加老龄小鼠的肌肉力量(与老龄小鼠对照组相比,GABA 剂量分别为 10 或 30 毫克/千克/天时,分别增加 41% 和 70%,p < 0.05)和肌肉质量(股四头肌:分别增加 28% 和 46%;腓肠肌:分别增加 12% 和 19%,p < 0.05)。这种增加伴随着股四头肌和腓肠肌横截面积(CSA)的增加(p < 0.05)。服用 GABA 能提高血清中 IGF-1 的水平(p < 0.05),从而激活肌肉蛋白质的合成。我们发现,GABA 可通过激活 Akt/mTOR/FoxO3a 信号通路,调节肌肉蛋白降解,从而抑制肌肉疏松症。GABA 还能调节炎症反应,而炎症反应是与年龄有关的肌肉萎缩的标志。老年小鼠腓肠肌和脾脏中的F4/80 + CD11b + 总巨噬细胞比率明显增加,尤其是M1巨噬细胞比率增加。然而,服用 GABA 能有效抑制 M1 巨噬细胞(腓肠肌:-40%,-53%;脾脏:-22%,-26%,p <0.05)。主要由 M1 巨噬细胞分泌的促炎细胞因子如 TNF-α 和 IL-6 也会因 GABA 的治疗而减少(TNF-α:-24%,-27%;IL-6:-45%,-59%,p <0.05)。我们认为,GABA 具有作为一种物质的潜力,可有效解决肌肉疏松症,并提高老年人的整体寿命和福祉。
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来源期刊
Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle Medicine-Orthopedics and Sports Medicine
自引率
12.40%
发文量
0
期刊介绍: The Journal of Cachexia, Sarcopenia, and Muscle is a prestigious, peer-reviewed international publication committed to disseminating research and clinical insights pertaining to cachexia, sarcopenia, body composition, and the physiological and pathophysiological alterations occurring throughout the lifespan and in various illnesses across the spectrum of life sciences. This journal serves as a valuable resource for physicians, biochemists, biologists, dieticians, pharmacologists, and students alike.
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