Body Temperature: The Key to Anti-aging? A Study in a Nature Sub-journal Shows: Activating the "Energy-saving Mode" Significantly Slows Down Aging

In nature, in order to cope with food scarcity or harsh environmental conditions, many mammals have their own unique survival strategies. For example, some animals choose to enter a state of torpor, while others hibernate. During torpor, an animal's metabolic rate significantly decreases, and its core body temperature drops. This state can last for several hours or even days. Hibernation, on the other hand, is a seasonal behavior composed of multiple torpor periods, during which the animal will periodically wake up and return to its normal body temperature. In simple terms, torpor is a short-term and flexible "energy-saving mode," while hibernation is a long-term and deep dormancy "survival strategy."

Some earlier studies have found that torpor and hibernation seem to be related to an extended lifespan in animals. However, until now, it has remained unclear how torpor affects the aging process and what the underlying mechanisms are. Additionally, it has been an open question whether it is possible to slow down aging and extend healthy lifespan by artificially inducing a state of low body temperature and low metabolism.

Recently, researchers from the Massachusetts Institute of Technology published a research paper titled "A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan" in the journal *Nature Aging*. This study has made a significant discovery: inducing a torpor-like state (TLS) in mice can effectively slow down the epigenetic aging of their blood and extend their healthy lifespan. This research not only reveals that body temperature plays an independent and crucial role in the regulation of aging but also provides a new target for anti-aging research. Moreover, it fully demonstrates the powerful capabilities of the chemogenetic model in analyzing complex physiological processes.

In this study, the research team employed a clever approach. They activated the anterior ventral medial and lateral preoptic areas (avMLPA) in the preoptic area (POA) of the hypothalamus in mice through chemogenetics, successfully inducing a torpor-like state (TLS). Mice in the TLS state exhibited a series of obvious changes: the core body temperature decreased by an average of 7°C, the metabolic rate dropped by 56%, food intake reduced by 81%, and there was also a significant decrease in activity levels.

To simulate the natural hibernation pattern, the research team exposed the mice to repeated cycles of TLS. The results were astonishing: the rate of epigenetic aging in the blood of mice that were in a long-term TLS state slowed down by 76%! Moreover, this anti-aging effect was cumulative and persistent. Even after the TLS state was terminated, this effect continued for three months. In addition, this deceleration of epigenetic aging was not uniform across all tissues. For example, the epigenetic age of the liver decreased by 20%, while there were no significant changes in the kidneys and the cerebral cortex.

The researchers also found that the frailty index of mice in the TLS state was significantly lower than that of the control group. This indicates that the rate of decline in physiological function was reduced in these mice, and their healthy lifespan was significantly improved.

Upon in-depth exploration of the underlying mechanisms, it was discovered that the decrease in body temperature is the core factor contributing to the slowdown of aging and the extension of healthy lifespan. By controlling the environmental temperature to rule out the influence of changes in metabolic rate, it was found that simply reducing the body temperature was sufficient to slow down the epigenetic aging of the blood. Conversely, when simulating the decrease in metabolic rate and food intake associated with TLS but without a corresponding decrease in body temperature, the anti-aging effect of TLS could not be replicated.