Nature is often the best model of science. For almost a century, scientists have tried to recreate the capacity of certain mammals and birds to survive to extreme environmental conditions for brief or prolonged periods by going into torpor, when their body temperature and their decrease in the metabolic rate, allowing them to preserve energy and heat.
Inspired by nature, Hong Chen, professor of biomedical engineering at the McKelvey School of Engineering and Neurosurgery at Washu Medicine, and an interdisciplinary team induced a reversible state of torpor in mice, using ultrasonic focused to stimulate the preoptic zone of the hypothalamus in the brain, which bodily and metabolism. In addition to the mouse, which naturally enters the torpor, Chen and his team induced torpor in a rat, which does not. Their results, published in 2023 in Metabolism of natureshowed the first non -invasive and safe method to induce a state of torpor by targeting the central nervous system.
From now on, the team is translating induced or synthetic torpor into potential solutions for humans, for example when there is a reduced blood flow to tissues or organs, to preserve organs for transplantation or to protect radiation during space trips.
Conventional medical interventions focus on increasing energy supply, such as restoration of blood flow to the brain after a stroke. Synthetic torpor seeks to do the opposite by reducing energy demand.
“The ability of synthetic torpor to regulate the metabolism of the whole body promises to transform medicine by offering new strategies for medical interventions,” said Chen in an article of perspective published in Metabolism of nature July 31.
Synthetic torpor has been successfully used in preclinical models with drugs and specialized targeting of the neural circuit, but there are challenges to adapt these methods for humans. Previous human trials with hydrogen sulfide were interrupted early due to safety problems.
“Our challenges include overcoming it the metabolic differences between animals and humans, the choice of good dose of drugs and the creation of means to allow a reversible state in the form of a torpor,” said Wenbo Wu, a doctoral student in biomedical engineering in the laboratory of Chen and the first author of the Riken Paper, a collaboration between Dynamics Research biosysm in Japan. “Collaboration between scientists, clinicians and ethicians will be essential to develop safe, effective and scalable solutions so that synthetic torpor becomes a practical medicine solution. »»
The Chen team, including Yaoheng (Mack) Yang, who was a postdoctoral research associate in his laboratory and is now a deputy professor of biomedical engineering at the University of Southern California, targeted the neural circuit with their torpor solution induced in mice. They created a portable ultrasound transducer to stimulate neurons in the preoptic area of the hypothalamus. When stimulated, mice showed a drop in body temperature of approximately 3 degrees C for about an hour. In addition, mouse metabolism has shown a change compared to the use of carbohydrates and fats for energy at only fat, a key characteristic of torpor and their heart rate has dropped by around 47%, all at room temperature.
Ultrasound is the only non -invasive energy modality capable of securely penetrating the skull and precisely targeting the deep brain structures. Although ultrasonic neuromodulation lacks cell type specificity compared to genetic neuromodulation, it provides a non -invasive alternative to induce synthetic torpor without the need for genetic changes. “”
Hong Chen, professor of biomedical engineering, McKelvey School of Engineering and Neurosurgery, Washu Medicine
Chen and his team indicate that synthetic torpor offers a promising therapeutic strategy with additional applications, in particular the inhibition of tumor growth and the potential development of new therapies for diseases related to TAU proteins, such as Alzheimer’s disease. However, many things remain unknown on how brain regions, peripheral organs and cellways coordinate metabolic suppression and excitement. Researchers must also study long -term risks and potential side effects and call for more preclinical studies and technological innovations that will facilitate a double approach, which would include the modulation of neural circuits associated with hypometabolism and influencing peripheral metabolic routes through systemic interventions, such as drugs or peripheral neuromodulation.
“Synthetic torpor is no longer just a theoretical concept – it is an emerging field with the potential to redefine medicine,” said Chen. “The Commission of Fundamental Neurosciences, Bio-Engineering and Translational Medicine will be the key to overcoming current challenges and advancing synthetic torpor to real world applications. Synthetic torpor could go from scientific curiosity to human reality through interdisciplinary collaborations. »»