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The NO-Age and NO-AD Seminar Number 25 by Dr. Jane Reznick, CECAD Research Center University Hospital Cologne
‘Molecular insights into cardiometabolic health from a long-lived mammal the naked mole-rat’

The naked mole–rat has recently emerged as a rodent model of interest to biomedicine due to its extraordinarily long and healthy lifespan (>36 years). Naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose and sucrose. Global expression of fructose specific transporter GLUT5 and ketohexokinase (KHK) were identified in the naked mole-rat suggesting a rewired transcriptome to enable fructose metabolism across the entire organism. We have combined transcriptomics and in vivo stable isotope resolved metabolomics analyses and showed that under hypoxia the naked mole-rat activates the polyol pathway to synthesise fructose in the heart whilst enhancing fructolysis in heart and brain. Unexpectedly, when supplied with fructose mouse brain also showed a preference for fructose under hypoxic conditions. Our findings reveal a new role for fructose metabolism under hypoxic contexts and suggest that fructose dependent metabolism could be protective under hypoxic conditions. Our analysis identified further unique features in the naked mole-rat heart at the transcriptomic and metabolomic level which serve as adaptive mechanisms to combat hypoxia and promote longevity thus providing novel insights into the biology of low oxygen tolerance and a long healthspan.

Sep 20, 2021 02:00 PM in Oslo

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