Inspiration gleaned from the natural world has long propelled scientific innovation, particularly in the realm of medicine and bioengineering. Over the past century, researchers have intensively explored the phenomenon of torpor — a biological state wherein certain mammals and birds drastically reduce their metabolic rate and body temperature to conserve energy under extreme environmental conditions. This innate survival mechanism enables these animals to endure periods of scarcity or harsh climates by effectively “pausing” their physiological demands. Intriguingly, a newly emerging frontier in biomedical science aims to mimic this torpor-like state synthetically, with transformative implications for human health and medicine.
At the forefront of this pioneering work is Hong Chen, a professor of biomedical engineering at the McKelvey School of Engineering and a neurosurgeon at WashU Medicine. Chen and her interdisciplinary team have recently achieved a milestone in inducing a reversible torpor-like state using a noninvasive technique. Their method centers on delivering focused ultrasound stimulation to a precise region in the brain known as the hypothalamus preoptic area, a critical hub responsible for the homeostatic regulation of body temperature and metabolic function. Remarkably, this approach not only replicated torpor in mice, natural torpor-capable mammals, but also induced the state in rats, which do not typically enter torpor, signaling its potential broad applicability.
The induction of synthetic torpor through ultrasound neuromodulation harnesses a unique capability: the ability to penetrate the skull safely and activate deep brain structures with surgical precision without the need for invasive implants or genetic modification. The hypothalamus preoptic area, when stimulated, orchestrates systemic metabolic downregulation manifesting in several hallmark features of natural torpor. In Chen’s experiments, mice treated with the wearable ultrasound transducer exhibited a controlled drop in core body temperature by approximately 3 degrees Celsius sustained for around an hour at room temperature. Additionally, these mice underwent a metabolic fuel shift, curtailing carbohydrate metabolism in favor of fat utilization, a key metabolic hallmark of the torpor state. Concurrently, their heart rates decreased sharply by nearly half, further underscoring the systemic nature of induced metabolic suppression.
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This noninvasive ultrasound-based method marks the first of its kind to safely and reversibly induce synthetic torpor in mammals by targeting neural circuits directly. It stands in sharp contrast to prior approaches that relied on pharmaceuticals, including experimental human trials involving hydrogen sulfide, which were prematurely halted due to safety risks. While prior methodologies have exhibited the capacity to mediate hypometabolism pharmacologically or through complex neural modulation, they often lacked scalability or demonstrated potential for significant side effects. Ultrasound neuromodulation sidesteps many of these challenges, opening a new translational pathway towards harnessing synthetic torpor for clinical use.
Potential therapeutic applications of synthetic torpor extend across a vast spectrum of medical challenges. The classical paradigm in acute care focuses heavily on restoring and augmenting energy supply to compromised organs and tissues, such as the efforts to reestablish cerebral blood flow following ischemic strokes. Synthetic torpor retrenches this orthodoxy by seeking to proactively reduce energy demands throughout the body. This metabolic reprogramming offers a promising avenue for protecting vulnerable tissues during periods of compromised oxygenation or nutrient delivery, thereby mitigating irreversible damage.
One of the most tantalizing prospects lies in organ preservation for transplantation. Current preservation techniques limit the viability window of donor organs substantially, impeding the transplantation process logistically and medically. By inducing a synthetic torpor-like state, metabolic activity in organs destined for transplantation could be dramatically suppressed, potentially prolonging their functional viability outside the body. Beyond transplantation, the protective metabolic downscaling could extend to radiation shielding in the context of long-duration space travel, where human physiology must endure prolonged exposure to cosmic radiation and oxygen deprivation.
Despite the promise, significant translational hurdles remain. Chief among these is the challenge of interspecies metabolic variation: results gleaned from small animal models such as mice and rats do not always extrapolate linearly to human physiology. Moreover, defining the precise parameters and dosages required to induce torpor safely, reversibly, and effectively in humans entails extensive research. This complexity arises from fundamental differences in neural circuitry, metabolic regulation, and systemic response dynamics between species. As Wenbo Wu, a doctoral student in Chen’s lab and first author of a recently published Perspectives article, articulates, collaboration spanning neuroscience, clinical medicine, engineering, and ethics is essential to realize synthetic torpor’s full potential in human health.
The potential implications of synthetic torpor extend well beyond acute organ protection. Preliminary data suggest possible applications in oncology—with metabolic suppression potentially inhibiting tumor growth—and neurodegenerative diseases linked to tau protein pathology, such as Alzheimer’s disease. Metabolic downregulation could retard pathogenic protein accumulation and cellular stress processes, offering novel therapeutic avenues. Nevertheless, the underlying mechanisms linking brain regions, peripheral organ systems, and cellular metabolic pathways during induced hypometabolism remain incompletely understood. Hence, ongoing research must also rigorously evaluate long-term safety, risks, and the possibility of unintended side effects.
Technological innovation will play a pivotal role in further advancing synthetic torpor. Chen’s team advocates for a dual intervention strategy: combining neural circuit modulation with peripheral systemic treatments, potentially including targeted pharmaceuticals or peripheral neuromodulation techniques. Such an integrative approach could more comprehensively recapitulate the intricate physiological balance of natural torpor, optimally suppressing metabolism system-wide while preserving reversibility and safety.
As a testament to the multidisciplinary synergy powering this breakthrough, Chen’s collaboration extends internationally, notably with Genshiro Sunagawa at Japan’s RIKEN Center for Biosystems Dynamics Research. This partnership underscores the global scientific community’s recognition of synthetic torpor’s transformative potential and the imperative for diverse expertise spanning molecular neuroscience, bioengineering, and clinical translational research.
The field of synthetic torpor is evolving rapidly from theoretical curiosity to an emerging paradigm with profound medical implications. By integrating fundamental neuroscience with cutting-edge bioengineering, researchers like Chen and her colleagues aim to rewrite the boundaries of therapeutic metabolic control. Their work introduces a viable, noninvasive pathway to inducing a torpor-like state, signaling a future wherein medical professionals might safely dial down human metabolism on demand to safeguard tissues, expand treatment windows, and innovate therapeutic strategies across a variety of diseases and clinical scenarios.
In Chen’s vision, the future of synthetic torpor hinges not only on technical refinement but on forging cross-disciplinary collaborations. Such alliances will bridge gaps between experimental models and human physiology, harmonizing innovation with ethical clinical translation. Ultimately, synthetic torpor may transition from a biological phenomenon exploited by animals into a powerful medical tool enabling new frontiers in patient care, trauma treatment, and beyond.
Subject of Research: Synthetic Torpor and Metabolic Regulation
Article Title: Synthetic torpor: Advancing metabolic regulation for medical innovations
News Publication Date: July 31, 2025
Web References:
Perspectives Article DOI: https://www.nature.com/articles/s42255-025-01345-3
Original Findings DOI: https://www.nature.com/articles/s42255-023-00804-z
References:
Wu W, Sunagawa GA, Chen H. Synthetic torpor: Advancing metabolic regulation for medical innovations. Nature Metabolism, July 31, 2025. DOI: 10.1038/s42255-025-01345-3
Keywords: Medical equipment, Biomedical engineering, Regenerative medicine
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