Wu Wenbo, Sunagawa Genshiro A, Chen Hong
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA.
Nat Metab. 2025 Aug;7(8):1511-1523. doi: 10.1038/s42255-025-01345-3. Epub 2025 Jul 31.
Torpor is a naturally occurring state of metabolic suppression that enables animals to adapt and survive extreme environmental conditions. Inspired by this adaptation, researchers have pursued synthetic torpor-an artificially induced, reversible hypometabolic state with transformative medical potential. Achieving synthetic torpor has been pursued for over a hundred years, with earlier work focused on identifying drugs for systemically suppressing metabolism. Breakthroughs in 2020 identified key torpor-regulating neurons in mice, opening new opportunities for neuromodulation-based metabolic control. Synthetic torpor has been applied in animal models for various medical applications, including ischaemic protection, organ preservation, radiation protection and lifespan extension. This Perspective examines the fundamental concepts of natural torpor, advances in approaches to induce synthetic torpor and medical applications of synthetic torpor. The capability of synthetic torpor to suppress whole-body metabolism has the potential to transform medicine by offering novel strategies for medical interventions.
蛰伏是一种自然发生的代谢抑制状态,能使动物适应并在极端环境条件下生存。受这种适应性的启发,研究人员一直在探索人工诱导的、具有变革性医学潜力的可逆性低代谢状态——合成蛰伏。实现合成蛰伏的研究已经进行了一百多年,早期的工作主要集中在寻找系统性抑制新陈代谢的药物。2020年的突破确定了小鼠中关键的蛰伏调节神经元,为基于神经调节的代谢控制开辟了新机会。合成蛰伏已应用于各种医学应用的动物模型中,包括缺血保护、器官保存、辐射防护和寿命延长。本观点文章探讨了自然蛰伏的基本概念、诱导合成蛰伏方法的进展以及合成蛰伏的医学应用。合成蛰伏抑制全身新陈代谢的能力有可能通过提供新的医学干预策略来变革医学。