On the first day of Siniša Hrvatin’s Introduction to Biology class, he asks his Massachusetts Institute of Technology undergraduate students the same question: “What technology could emerge in your lifetime that could profoundly benefit society — and how can you help make it a reality?”  

It’s the question that the HHMI Freeman Hrabowski Scholar has been asking himself since childhood — and it led him to the topic of hibernation, a state that he considers rich with largely untapped scientific and medical potential.

In hibernating animals, biological processes slow dramatically, yet cells remain viable and resilient to stress, suggesting mechanisms that could one day be harnessed to improve human health.  

“Hibernation allows an animal to slow down biological processes — essentially, to turn down the dial of time,” Hrvatin explains.  

A Survival State with Surprising Benefits 

Hrvatin now studies hibernation as well as the related state, torpor. Many people use these terms interchangeably, but they are distinct. Torpor is a short-term, controlled drop in metabolism and temperature. Hibernation is the longer seasonal pattern built from repeated episodes of torpor.  

These states vary widely across species. At the mild end, fasting mice can enter a brief daily torpor, slightly lowering their body temperature for a few hours before returning to normal. At the extreme, arctic squirrels may enter torpor for weeks at a time, dropping their body temperature to 0°C and only briefly rousing during the season.  

Regardless of the form that it takes, some aspects of hibernation appear to be consistent. Animals that hibernate tend to live longer than their related counterparts and show greater resilience to cold, aging-related decline, and some disease processes, including cancer. 

Like anything else, hibernation has drawbacks. Hibernating animals are largely immobile, making them easy prey. Their immune systems are also suppressed — a cost partly offset by slower pathogen growth in extreme cold. Nevertheless, as an adaptation meant to help animals endure inhospitable environments, hibernation is a powerful survival mechanism.  

How Hibernation Slows the Biological Clock 

Scientists have long known that hibernation expands lifespan, but the mechanism has remained unclear.  

“Torpor is characterized by several different physiological outcomes at once: a lower metabolic rate, change in core body temperature, and caloric restriction,” Hrvatin explains. “We wanted to engineer a controllable way to induce a torpor-like state so we could disentangle which of these mechanisms might be driving longevity.”  

Hrvatin’s lab at the Whitehead Institute for Biomedical Research at MITexternal link, opens in a new tab identified the neuronsexternal link, opens in a new tab that regulate daily torpor. They used this insight to induce an extended, torpor-like state in mice and test which factors drive its benefits. They tapped into the “blood epigenetic clock,” a molecular biomarker that measures how fast or slow a creature is aging compared to their chronological age, as well as specific frailty metrics, adapted from human clinical settings. 

By carefully manipulating the amount of food the mice received, the room temperature, and other settings that affect metabolism, they tested all three variables. They found that, much more than caloric restriction or changes in metabolic rate, greater drops in body temperature led to biomarkers and metrics associated with improvements in healthexternal link, opens in a new tab.   

Finding Hibernation’s Neural Switch 

Recognizing that induced torpor is significantly shallower than the naturally occurring deep torpor of hibernating animals, Hrvatin’s team next studied hibernating Syrian hamsters to determine which neurons signal entry into deep torpor.   

They identified the anterior preoptic area of the hypothalamus as a key regulating region. Using single-cell profiling and new genetic tools, they then pinpointed a specific group of cellsexternal link, opens in a new tab — Samd3-positive neurons  — active during hibernation entry. These neurons proved both necessary and sufficient to trigger a prolonged, hibernation-like state. It is the first time scientists have defined a specific neural population that can switch on a hibernation-like state. 

Now that he’s identified the specific neural trigger that induces key features of torpor and hibernation, Hrvatin plans to study whether other, non-hibernating species — including mammals — possess these neurons, and whether they can be stimulated in animals that don’t normally hibernate.  

The work represents a step toward the kind of future-shaping objectives he has long challenged himself, and his students, to imagine: a technology that could affect how humans endure and recuperate from disease and stress. 

“If we can harness these mechanisms,” Hrvatin says, “we could transform how we treat disease, injury, and aging.”