Molecular Mechanisms of Hibernation in Mammalian Systems

Hibernation in mammals represents a profound physiological adaptation enabling survival through prolonged periods of limited resources and extreme environmental stress. At the molecular level, hibernation is orchestrated by coordinated suppression of whole-body metabolic rate and body temperature, coupled with precise regulation of energy utilisation, tissue protection and cellular homeostasis. Central neural circuits within the hypothalamus integrate environmental cues and hormonal signals to trigger entry into torpor, while peripheral organs implement tissue-specific programmes. These include repression of mitochondrial respiration and induction of lipid catabolic pathways in adipose depots, activation of protein biosynthesis and inhibition of proteolysis in muscle and heart to prevent atrophy, and upregulation of anti-apoptotic and DNA repair pathways in the brain to ward off ischaemia–reperfusion injury. Epigenetic modifications, non-coding RNAs and specialised ion channels further refine the depth and duration of metabolic depression. The reversible nature of these mechanisms has inspired translational research aimed at exploiting hibernation-like states for organ preservation, metabolic disease management and neuroprotection in clinical settings.

Research from Nature Portfolio

Recent studies have demonstrated non-invasive induction of a torpor-like hypometabolic state in rodents via targeted transcranial ultrasound stimulation of preoptic hypothalamic neurons. This approach activates TRPM2 ion channels, engages dorsomedial hypothalamic circuits and suppresses thermogenic brown adipose tissue, establishing a blueprint for remote control of metabolic suppression. Complementing this, transcriptomic analysis of grizzly bears across seasonal cycles has revealed extensive remodelling in adipose, liver and skeletal muscle. Hibernation is characterised by downregulation of insulin signalling and proteolytic genes alongside coordinated upregulation of anabolic and lipid oxidation networks. Shared gene signatures across tissues suggest a conserved regulatory module that underlies reversible metabolic depression and organ protection, providing molecular targets to mimic hibernation physiology in non-hibernators.

Molecular Mechanisms of Hibernation in Mammalian Systems publication trend

The graph below shows the total number of articles in molecular mechanisms of hibernation in mammalian systems across all publications each year (not limited to Nature Index journals).

Technical terms

Torpor: A reversible state of reduced metabolic rate and lowered body temperature enabling energy conservation.

Hypometabolism: A downregulated metabolic condition with suppressed oxygen consumption and ATP turnover.

Brown Adipose Tissue (BAT): A specialised fat depot that generates heat via uncoupled mitochondrial respiration during arousal from torpor.

Transcriptomics: Genome-wide analysis of RNA transcripts used to profile gene expression changes across tissues and physiological states.

Interbout Arousal: Periodic return to normothermia and metabolic activity during prolonged hibernation.

Neuroprotection: Cellular mechanisms that preserve neuronal integrity under conditions of low perfusion and oxidative stress.

References

1. Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound. Nature Metabolism (2023).
2. Modulation of gene expression in heart and liver of hibernating black bears (Ursus americanus). BMC Genomics (2011).
3. Seasonal and Regional Differences in Gene Expression in the Brain of a Hibernating Mammal. PLOS ONE (2013).
4. Hibernation induces widespread transcriptional remodeling in metabolic tissues of the grizzly bear. Communications Biology (2019).
5. The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms†. Frontiers in Physiology (2021).