Metabolic remodelling of mice by hypoxic-hypercapnic environment: imitating the naked mole-rat

Biogerontology. 2020 Apr;21(2):143-153. doi: 10.1007/s10522-019-09848-9. Epub 2019 Oct 31.


We hypothesised that hypoxic-hypercapnic environment (HHE) could induce metabolic suppression and associated benefits for health and longevity, as observed in the naked-mole rat (NMR). We developed a model of self-produced HHE (similar to a natural habitat of NMRs), which is simple, reliable and natural, and does not require external sources of gases or complex technical equipment. Here, we showed for the first time that a chronic exposure of mice to HHE could be a unique tool for NMR-like metabolic remodeling, resulting in a long-term and substantial decrease in metabolic rate, body temperature, and food consumption, without significant changes in expression of stress-related genes. Unexpectedly, the HHE accelerated skin wound healing, despite the lower energy expenditure. The self-produced HHE could be considered a model of voluntary calorie restriction. All in all, a chronic exposure to HHE offers a potential of being a lifespan-extending intervention as well as an efficient tool for treating the overweight and associated metabolic disorders.

Keywords: Age; Hypercapnia; Hypometabolism; Hypothermia; Hypoxia; Mice; Voluntary calorie restriction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization*
  • Age Factors
  • Animals
  • Body Temperature Regulation
  • Caloric Restriction
  • Ecosystem*
  • Energy Metabolism*
  • Hypercapnia / metabolism*
  • Hypercapnia / physiopathology
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology
  • Longevity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mole Rats
  • Species Specificity
  • Time Factors
  • Wound Healing