Orentreich Foundation for the Advancement of Science, Inc., 855 Route 301, Cold Spring, NY, 10516, USA.
Sci Rep. 2023 Nov 23;13(1):20609. doi: 10.1038/s41598-023-47676-7.
Sulfur amino acid restriction (SAAR)-the reduction of methionine and cysteine concentrations either in the diet or by genetic manipulation-promotes health span and extends lifespan, but its effects on physical activity remain unclear. We investigated whether age of diet initiation and biological sex could influence physical activity in mice fed either a control diet (CF, 0.86% methionine w/w) or SAAR (0.12% methionine w/w). Quadriceps femoris muscle mass is smaller in SAAR than in CF mice. Young mice fed a chronic SAAR diet at 8 weeks of age exhibited improved wire hang and running wheel activities compared to young CF mice, while aged mice showed comparable results. The effects of chronic SAAR on physical activity was mildly influenced by sex as observed in middle-aged male SAAR mice who showed minor improvements than CF males while middle-aged females displayed no discernible effects. Muscle mass is minimally affected by changes in markers of protein synthesis, autophagy and atrophy. Improvements to physical activity in young SAAR mice could be partially attributed to increased skeletal muscle mitochondrial activity. Furthermore, SAAR in C2C12 myotubes increased citrate synthase protein expression and enhanced succinyl dehydrogenase enzyme activity compared to CF myotubes. Overall, our data reveal that SAAR can improve mouse physical activity without compromising muscle proteostasis. This is partially due to enhanced mitochondrial activity, but the effects are influenced by age of diet initiation and sex.
硫氨基酸限制（SAAR）-减少饮食或遗传操作中的蛋氨酸和半胱氨酸浓度-可促进健康寿命并延长寿命，但对体力活动的影响尚不清楚。我们研究了饮食起始年龄和生物性别是否会影响分别用对照饮食（CF，0.86％蛋氨酸 w/w）或 SAAR（0.12％蛋氨酸 w/w）喂养的小鼠的体力活动。与 CF 小鼠相比，SAAR 中的股四头肌肌肉质量较小。在 8 周龄时接受慢性 SAAR 饮食喂养的年轻小鼠在挂线和跑步轮活动方面表现出优于年轻 CF 小鼠的表现，而老年小鼠则表现出相似的结果。慢性 SAAR 对体力活动的影响因性别而异，中年雄性 SAAR 小鼠的影响较小，而中年雌性小鼠则没有明显的影响。肌肉质量受蛋白质合成、自噬和萎缩标志物变化的影响较小。年轻的 SAAR 小鼠体力活动的改善部分归因于骨骼肌线粒体活性的增加。此外，与 CF 肌管相比，C2C12 肌管中的 SAAR 增加了柠檬酸合酶蛋白表达并增强了琥珀酰脱氢酶酶活性。总体而言，我们的数据表明，SAAR 可以改善小鼠的体力活动而不会损害肌肉蛋白稳态。这部分是由于线粒体活性增强，但作用受饮食起始年龄和性别的影响。
