Fig. 7.

Neurons display high energy consumption with metabolic consumption of the brain representing 20% of the whole-body oxygen uptake. With increased evolutionary pressures as human cognitive and motor skills were fine-tunes neuronal energy demands increased. Energy deficiency induces mitochondrial dysfunction with failure of ATP production. Aging and senescence impair energy balance in homeostasis. At a cellular level this increases the tendency to protein degradation, aggregation and mis-localization with subsequent development of neurodegeneration (Henderson et al., 2022).