Abstract
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.
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Abbreviations
- CR:
-
Calorie restriction
- FT3:
-
Free triiodothyronine
- FT4:
-
Free thyroxine
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- HHE:
-
Hypoxic-hypercapnic environment
- HSP90AA1:
-
Heat Shock Protein 90 Alpha Family Class A Member
- i.p.:
-
Intraperitoneally
- MSCs:
-
Mesenchymal stem cells
- NMR(s):
-
Naked mole-rat(s)
- qPCR:
-
Quantitative real time polymerase chain reaction
- Vo2 :
-
Oxygen consumption
- Vco2 :
-
Carbon dioxide production
- UCP2:
-
Mitochondrial uncoupling protein 2
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Acknowledgements
We thank Dr. Irina Pishel for her assistance in conducting the experiments. This work was supported in part by the Fund in Memory of Dr. Amir Abramovich (to V.E.F.).
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Online Resource 2 (a) The head skin excision model, and (b) time-course of skin wound closure in young male C57Bl/6 mice upon chronic exposure to self-produced HHE. Each mouse was subjected to a single head punch wound. Wound area was expressed as percentage of the original wound size (PPTX 194 kb)
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Tolstun, D.A., Knyazer, A., Tushynska, T.V. et al. Metabolic remodelling of mice by hypoxic-hypercapnic environment: imitating the naked mole-rat. Biogerontology 21, 143–153 (2020). https://doi.org/10.1007/s10522-019-09848-9
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DOI: https://doi.org/10.1007/s10522-019-09848-9