Biozentrum, University of Basel, Basel, Switzerland.
Swiss Institute of Bioinformatics, Basel, Switzerland.
Commun Biol. 2024 Aug 10;7(1):974. doi: 10.1038/s42003-024-06679-4.
Calorie restriction (CR) and treatment with rapamycin (RM), an inhibitor of the mTORC1 growth-promoting signaling pathway, are known to slow aging and promote health from worms to humans. At the transcriptome and proteome levels, long-term CR and RM treatments have partially overlapping effects, while their impact on protein phosphorylation within cellular signaling pathways have not been compared. Here we measured the phosphoproteomes of soleus, tibialis anterior, triceps brachii and gastrocnemius muscles from adult (10 months) and 30-month-old (aged) mice receiving either a control, a calorie restricted or an RM containing diet from 15 months of age. We reproducibly detected and extensively analyzed a total of 6960 phosphosites, 1415 of which are not represented in standard repositories. We reveal the effect of these interventions on known mTORC1 pathway substrates, with CR displaying greater between-muscle variation than RM. Overall, CR and RM have largely consistent, but quantitatively distinct long-term effects on the phosphoproteome, mitigating age-related changes to different degrees. Our data expands the catalog of protein phosphorylation sites in the mouse, providing important information regarding their tissue-specificity, and revealing the impact of long-term nutrient-sensing pathway inhibition on mouse skeletal muscle.
热量限制(CR)和雷帕霉素(RM)治疗,一种 mTORC1 生长促进信号通路的抑制剂,已知可减缓衰老并促进从蠕虫到人类的健康。在转录组和蛋白质组水平上,长期 CR 和 RM 治疗具有部分重叠的作用,而它们对细胞信号通路中蛋白质磷酸化的影响尚未进行比较。在这里,我们测量了从接受对照、热量限制或 RM 饮食的成年(10 个月)和 30 个月(老年)小鼠的比目鱼肌、胫骨前肌、肱三头肌和腓肠肌中的磷酸蛋白质组。从 15 个月大开始,我们可重复地检测到并广泛分析了总共 6960 个磷酸化位点,其中 1415 个不在标准库中。我们揭示了这些干预措施对已知的 mTORC1 途径底物的影响,CR 显示出比 RM 更大的肌肉间变异性。总体而言,CR 和 RM 对磷酸蛋白质组具有大致一致但数量上不同的长期影响,在不同程度上减轻了与年龄相关的变化。我们的数据扩展了小鼠中蛋白质磷酸化位点的目录,提供了有关其组织特异性的重要信息,并揭示了长期营养感应途径抑制对小鼠骨骼肌的影响。