Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles.
Chris G FaulkesThomas R EykynJan Lj MiljkovicJames D GilbertRebecca L CharlesHiran A PragNikayla PatelDaniel W HartMichael P MurphyNigel C BennettDunja AksentijevićPublished in: Nature communications (2024)
The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.
Keyphrases
- genome wide
- cardiovascular disease
- south africa
- oxidative stress
- ischemia reperfusion injury
- left ventricular
- endothelial cells
- healthcare
- physical activity
- poor prognosis
- type diabetes
- metabolic syndrome
- heart failure
- copy number
- mass spectrometry
- risk assessment
- mental health
- gene expression
- transcription factor
- weight loss
- climate change
- cardiovascular events
- cardiovascular risk factors
- human health