Table 1.

Signalling pathways that influence ageing in model organisms and brain ageing in mammals

Pathway	Effects on ageing of model organism	Effects on mammalian brain ageing
Insulin/IGF-1 signalling	Decreased signalling promotes increased stress resistance and lifespan	Decreased signalling promotes decreased Alzheimer’s disease pathology; paradoxically, increased signalling may be neuroprotective
TOR signalling	Decreased signalling causes increased lifespan, increased autophagy and decreased protein translation	Regulation of autophagy and protein homeostasis may modulate toxic-protein aggregation in neurodegenerative disease
Mitochondrial function	Severely decreased function causes decreased lifespan, but modestly decreased function can cause increased lifespan	Progressively decreasing function during ageing contributes to decline and pathology. However, preliminary evidence suggests that modestly decreased function may engage beneficial pathways
Sirtuins	Can increase or decrease lifespan in different contexts	Can be neuroprotective or detrimental to neurons, depending on context
Caloric restriction	Optimal caloric restriction causes increased lifespan	Increased preservation of cognitive function during ageing

IGF-1, insulin-like growth factor 1; TOR, target of rapamycin.