During a long-duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed-loop bioregenerative life-support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics 'hibernation', could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation-like state (synthetic torpor) in non-hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (Tb ) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor-arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor-arousal transition in both non-flying hibernating mammals and non-hibernating species, and aim to provide translational insights into long-duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long-duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.

中文翻译：

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人类麻木：将大自然的洞察力转化为载人深空探险

在长期载人航天任务中，例如飞往火星及更远的地方，所有机组人员将在具有闭环生物再生生命支持系统的独立航天器中度过很长时间。节省资源和降低医疗风险，尤其是精神健康方面的风险，是阻碍人类深入太空探索的关键技术差距。在 1960 年代，几位科学家提出，模拟“冬眠”的人类新陈代谢受抑制的诱导状态可能是应对太空飞行中许多问题的理想解决方案。近年来，随着特定方法的引入，在非冬眠物种中诱导人工冬眠状态（合成麻木）变得越来越可行。自然麻木是一种迷人而又神秘的生理过程，其中代谢率 (MR)、在严酷的季节性条件下，降低身体核心温度 (Tb) 和行为活动以节省能量。它采用复杂的中枢神经网络来协调代谢减退、体温过低和活动减退的稳态状态，以应对环境挑战。中枢神经系统 (CNS) 内的解剖和功能连接是控制合成麻木的核心。尽管已经取得了进展，但对活跃调节麻木-觉醒过渡的确切机制及其对神经功能和行为的深远影响（这些是安全和可逆的人类麻木的关键问题）仍然知之甚少。在这次审查中，我们特别强调阐述在非飞行冬眠哺乳动物和非冬眠物种中协调麻木-觉醒转变的中枢神经机制，并旨在为长期载人航天提供转化见解。此外，确定未来的困难和挑战将强调人类工程合成麻木的重要问题。我们认为，合成麻木可能不是载人长期航天飞行的唯一选择，但在可预见的未来，它是最可行的解决方案。从自然麻木研究中转化可用的知识不仅有利于载人航天，而且有利于许多试图操纵能量代谢和神经行为功能的临床环境。并旨在为长期载人航天飞行提供转化见解。此外，确定未来的困难和挑战将强调人类工程合成麻木的重要问题。我们认为，合成麻木可能不是载人长期航天飞行的唯一选择，但在可预见的未来，它是最可行的解决方案。从自然麻木研究中转化可用的知识不仅有利于载人航天，而且有利于许多试图操纵能量代谢和神经行为功能的临床环境。并旨在为长期载人航天飞行提供转化见解。此外，确定未来的困难和挑战将强调人类工程合成麻木的重要问题。我们认为，合成麻木可能不是载人长期航天飞行的唯一选择，但在可预见的未来，它是最可行的解决方案。从自然麻木研究中转化可用的知识不仅有利于载人航天，而且有利于许多试图操纵能量代谢和神经行为功能的临床环境。我们认为，合成麻木可能不是载人长期航天飞行的唯一选择，但在可预见的未来，它是最可行的解决方案。从自然麻木研究中转化可用的知识不仅有利于载人航天，而且有利于许多试图操纵能量代谢和神经行为功能的临床环境。我们认为，合成麻木可能不是载人长期航天飞行的唯一选择，但在可预见的未来，它是最可行的解决方案。从自然麻木研究中转化可用的知识不仅有利于载人航天，而且有利于许多试图操纵能量代谢和神经行为功能的临床环境。