# The Brown Bear and Hibernating Mammals as a Translational Model for Human Resilience: Insights for Space Medicine, Critical Care, and Austere Environments

## TL;DR

Hibernating animals like brown bears maintain health during long immobility, offering insights for preventing human health issues in space and critical care.

## Contribution

The paper identifies specific biological mechanisms in hibernators that could inspire new clinical approaches for human resilience in extreme conditions.

## Key findings

- Hibernating bears maintain muscle and bone health without exercise or food during hibernation.
- Hibernators recycle waste into nutrients and preserve retinal and heart function during prolonged inactivity.
- Mechanisms like RBM3, mTOR, and microbiome-based nitrogen salvage suggest translational applications for human health.

## Abstract

Spaceflight, bed rest, and critical illness each cause the body to be severely stressed. Muscle atrophy, bone loss of density, weakening of the heart, failure of the immune system, and sight impairment are very common. Diet and exercise interventions can halt these occurrences, but cannot hold them off entirely. Hibernating animals, however, like brown bears, tolerate months of immobility, fasting, and very low heart rates with no long-term consequences. They emerge from hibernation with preserved muscle strength, unbroken bones, and functioning brain and eyes. Even the waste products are recycled into useful nutrients rather than being lost. In this review, we explain how hibernating bears and smaller mammals achieve such resilience during hibernation. We highlight the natural mechanisms that keep their organs healthy and explore how these lessons may translate into novel clinical approaches. Applications range from protecting astronauts on extended spaceflight to helping recovery in critically ill patients and avoiding common age-related conditions such as osteoporosis, muscle wasting, and loss of memory. Studies of hibernators allow medicine to move beyond mending after damage and into preventing damage, and these consequences extend to both human spaceflight and terrestrial health.

Long-term spaceflight induces multisystem stress, including cardiovascular deconditioning, skeletal muscle atrophy, immune suppression, and neuro-ocular syndromes. Current countermeasures reduce symptoms but cannot replicate the synergistic resilience needed for extended missions or critical illness. Hibernating animals, specifically brown bears (Ursus arctos), survive prolonged immobility, starvation, and bradycardia without resultant pathology. This review incorporates adaptations observed in bears and certain torpid species, including reversible insulin resistance, suppression of muscle atrophy genes MuRF1 and Atrogin-1, and maintenance of the heart despite seasonal production decline. The thirteen-lined ground squirrels (Ictidomys tridecemlineatus) maintain retinal structure and synaptic stability throughout torpor, avoiding neuro-ocular complications despite prolonged inactivity. Mechanisms span from RBM3-dependent synaptic maintenance, titin isoform remodeling under the control of RBM20, mTOR and FOXO pathway regulation, remodeled hydrogen sulfide metabolism, and microbiome-mediated nitrogen salvage. These adaptations are different from human adaptation to microgravity and disuse and offer translational candidates for synthetic torpor, probiotic engineering, neuroprotection, and protein-sparing therapy. Hibernators are not passive stress subjects; they perform coordinated anticipatory responses in multiple organs. Comparing these systems in large and small hibernators, we aim to uncover a biologically realistic path to human resilience. These findings guide a shift from reactive, pharmacological measures for preserving human health during space flight, intensive care, and extreme environments towards proactive, biologically initiated measures.