FIGURE 3.

Physiological clustering of cell senescence, tissue hypoxemia and repressed NRF2–KEAP1 expression seem to be drivers of a state of inflammation, increased oxidative stress, mitochondrial dysfunction and metabolic imbalance that drives a cluster of burden of lifestyle diseases that associate with premature ageing. Novel approaches to intervene in this scenario include nutraceutical and synthetic senolytic and NRF2-stimulating therapies, as well novel interventions targeting tissue hypoxia, such as sodium glucose cotransporter 2 inhibitors, stimulators of mitochondrial biogenesis and hypoxia-inducible factor (HIF) stabilizers.