Department of Kinesiology, University of Wisconsin - Madison, Madison, WI, USA.
Department of Plastic and Reconstructive Surgery, The Ohio State University, Columbus, OH, USA.
J Nutr Health Aging. 2024 Jun;28(6):100219. doi: 10.1016/j.jnha.2024.100219. Epub 2024 Apr 5.
Pathological, age-related loss of muscle function, commonly referred to as sarcopenia, contributes to loss of mobility, impaired independence, as well as increased risk of adverse health events. Sarcopenia has been attributed to changes in both neural and muscular integrity during aging. Current treatment options are primarily limited to exercise and dietary protein fortification, but the therapeutic impact of these approaches are often inadequate. Prior work has suggested that a ketogenic diet (KD) might improve healthspan and lifespan in aging mice. Thus, we sought to investigate the effects of a KD on neuromuscular indices of sarcopenia in aged C57BL/6 mice.
A randomized, controlled pre-clinical experiment consisting of longitudinal assessments performed starting at 22-months of age (baseline) as well as 2, 6 and 10 weeks after the start of a KD vs. regular chow intervention.
Preclinical laboratory study.
Thirty-six 22-month-old mice were randomized into 2 dietary groups: KD [n = 22 (13 female and 9 male)], and regular chow [n = 15 (7 female and 8 male)].
Measures included body mass, hindlimb and all limb grip strength, rotarod for motor performance, plantarflexion muscle contractility, motor unit number estimations (MUNE), and repetitive nerve stimulation (RNS) as an index of neuromuscular junction transmission efficacy recorded from the gastrocnemius muscle. At end point, muscle wet weight and blood samples were collected to assess blood beta-hydroxybutyrate levels.
Primary analyses were two-way mixed effects ANOVA (diet and time × diet) to determine the effect of a KD on indices of motor function (grip, rotarod) and indices of motor unit (MUNE) and muscle (contractility) function.
Beta-hydroxybutyrate (BHB) was significantly higher at 10 weeks in mice on a KD vs control group (0.83 ± 0.44 mmol/l versus 0.42 ± 0.21 mmol/l, η = 0.265, unpaired t-test, p = 0.0060). Mice on the KD intervention demonstrated significantly increased hindlimb grip strength (diet, p = 0.0001; time × diet, p = 0.0030), all limb grip strength (diet, p = 0.0005; time × diet, p = 0.0523), and rotarod latency to fall (diet, p = 0.0126; time × diet, p = 0.0021). Mice treated with the KD intervention also demonstrated increased MUNE (diet, p = 0.0465; time × diet, p = 0.0064), but no difference in muscle contractility (diet, p = 0.5248; time × diet, p = 0.5836) or RNS (diet, p = 0.3562; time × diet, p = 0.9871).
KD intervention improved neuromuscular and motor function in aged mice. This pre-clinical work suggests that further research is needed to assess the efficacy and physiological effects of a KD on indices of sarcopenia.
病理性的、与年龄相关的肌肉功能丧失，通常称为肌肉减少症，导致运动能力丧失、独立性受损以及不良健康事件风险增加。肌肉减少症与衰老过程中神经和肌肉完整性的变化有关。目前的治疗选择主要限于运动和饮食蛋白质强化，但这些方法的治疗效果往往不足。先前的工作表明，生酮饮食（KD）可能会改善衰老小鼠的健康寿命和寿命。因此，我们试图研究 KD 对衰老 C57BL/6 小鼠的神经肌肉减少症指标的影响。
一项包括纵向评估的随机对照临床前实验，从 22 个月大（基线）开始，以及开始 KD 与常规饮食干预后 2、6 和 10 周进行。
临床前实验室研究。
36 只 22 个月大的小鼠被随机分为 2 种饮食组：KD [n = 22（13 只雌性和 9 只雄性）]和常规饮食 [n = 15（7 只雌性和 8 只雄性）]。
测量包括体重、后肢和四肢握力、旋转棒测试运动表现、跖屈肌收缩力、运动单位数量估计（MUNE）以及重复性神经刺激（RNS）作为从比目鱼肌记录的神经肌肉接头传递效率的指标。在终点时，收集肌肉湿重和血液样本，以评估血液β-羟丁酸水平。
主要分析采用双因素混合效应方差分析（饮食和时间×饮食），以确定 KD 对运动功能（握力、旋转棒）和运动单位（MUNE）和肌肉（收缩性）功能指标的影响。
KD 组小鼠的β-羟丁酸（BHB）在 10 周时明显高于对照组（0.83 ± 0.44 mmol/L 与 0.42 ± 0.21 mmol/L，η = 0.265，未配对 t 检验，p = 0.0060）。接受 KD 干预的小鼠表现出明显增强的后肢握力（饮食，p = 0.0001；饮食×时间，p = 0.0030）、四肢握力（饮食，p = 0.0005；饮食×时间，p = 0.0523）和旋转棒跌倒潜伏期（饮食，p = 0.0126；饮食×时间，p = 0.0021）。接受 KD 干预的小鼠还表现出 MUNE 的增加（饮食，p = 0.0465；饮食×时间，p = 0.0064），但肌肉收缩力（饮食，p = 0.5248；饮食×时间，p = 0.5836）或 RNS（饮食，p = 0.3562；饮食×时间，p = 0.9871）没有差异。
KD 干预改善了衰老小鼠的神经肌肉和运动功能。这项临床前工作表明，需要进一步研究 KD 对肌肉减少症指标的疗效和生理影响。
