Chen Wenkai, Xu Xueying, Zeng Zhidan, Zhou Mingsen, Chen Jiying, Hu Guangfu, Shen Anfu, Li Dapeng, Xiangjiang Liu
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
Nat Commun. 2025 Apr 5;16(1):3267. doi: 10.1038/s41467-025-58666-w.
The general association between longevity and energy metabolism has been well-documented for some time, yet the specific metabolic processes that regulate longevity remain largely unexplored. In contrast to the common active swimming daphnids (e.g., Daphnia sinensis), Simocephalus vetulus is notable for being sedentary and having a lower metabolic rate, yet it has a longer lifespan than D. sinensis. In this study, metabolomic analysis and drug validation experiments are employed to demonstrate that the lower pyruvate dehydrogenase (PDH) activity reduces the locomotor performance of S. vetulus and to identify PDH activity as a regulator of the lifespan of daphnids. Inhibition of PDH activity in daphnids by CPI-613 attenuates its ATP supply and locomotor performance but significantly induces longevity. The study also determines that the invertebrate neurotransmitter octopamine and temperature have a significant impact on PDH activity and modulate daphnids lifespan. And when the effects of temperature and octopamine on PDH activity are counteracted by inhibitors or agonists, the impact on lifespan becomes ineffective. These results support an important role for PDH in lifespan regulation and locomotor performance in daphnids and provide insights into the metabolic regulation of lifespan.
长寿与能量代谢之间的总体关联已经有一段时间被充分记录了，然而调节长寿的具体代谢过程在很大程度上仍未被探索。与常见的活跃游动的水蚤（如中华蚤）不同，老年低额溞以久坐不动和代谢率较低而著称，但它的寿命比中华蚤更长。在这项研究中，采用代谢组学分析和药物验证实验来证明较低的丙酮酸脱氢酶（PDH）活性会降低老年低额溞的运动能力，并将PDH活性确定为水蚤寿命的调节因子。CPI-613对水蚤PDH活性的抑制会减弱其ATP供应和运动能力，但会显著延长寿命。该研究还确定，无脊椎动物神经递质章鱼胺和温度对PDH活性有显著影响，并调节水蚤的寿命。并且当温度和章鱼胺对PDH活性的影响被抑制剂或激动剂抵消时，对寿命的影响就变得无效了。这些结果支持了PDH在水蚤寿命调节和运动能力中起重要作用，并为寿命的代谢调节提供了见解。
