Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, QC H3A 2B4, Canada; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, QC H4A 3J1, Canada.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Trends Endocrinol Metab. 2023 Mar;34(3):158-169. doi: 10.1016/j.tem.2023.01.003. Epub 2023 Jan 20.
We propose a two-mode (pursuit/maintenance) model of metabolism defined by usable resource availability. Pursuit, consisting of anabolism and catabolism, dominates when usable resources are plentiful and leads to the generation of metabolic waste. In turn, maintenance of a system is activated by elevated metabolic waste during resource depletion. Interaction with the environment results in pendulum-like swings between these metabolic states in thriveless attempts to maintain the least deleterious organismal state - ephemeral homeostasis. Imperfectness of biological processes during these attempts supports the accumulation of the deleteriome, driving organismal aging. We discuss how metabolic adjustment by the environment and resource stabilization may modulate healthspan and lifespan.
我们提出了一种由可用资源可用性定义的双模式(追求/维持)代谢模型。当可用资源丰富时,追求(由合成代谢和分解代谢组成)占主导地位,并导致代谢废物的产生。反过来,当资源耗尽时,代谢废物的升高会激活系统的维持。与环境的相互作用导致这些代谢状态在无生命的尝试中来回摆动,以维持最无害的机体状态——短暂的内稳态。在这些尝试中,生物过程的不完美性支持了 deleteriome 的积累,从而导致机体衰老。我们讨论了环境和资源稳定对代谢的调节如何调节健康寿命和寿命。