The Decline of Adaptive Homeostasis & Adaptive Proteostasis in Ageing

Abstract

Homeostasis classically considers a range of capacities, extending above and below a mean value, but cells, simple organisms, and even mammals, can temporarily expand the homeostatic range by undergoing transient adaptation. Such adaptive responses depend on altered gene expression, orchestrated by signal transduction pathways, such as Nrf2-Keap1 that allow us to cope with transient changes in environments, or stressors. Thus, in addition to the ‘normal’ range of homeostatic capabilities, there is an additional range of adaptive capacity that I propose should be called, ‘Adaptive Homeostasis’ (Davies, K.J.A. Adaptive Homeostasis. Molecular Aspects of Medicine. 49: 1–7, 2016). Important features of adaptive homeostasis include its mediation by discrete signal transduction pathways, as a result of small changes in signaling molecules/events, rather than in response to overt damage. Adaptive increases in oxidative stress-resistance through induction of the Proteasome and the mitochondrial Lon protease are examples of the plasticity of proteostasis (‘adaptive proteostasis’) and adaptive homeostasis in young mice, young flies, and young worms. However, adaptive proteostasis and homeostasis decline with age which may make older people more susceptible to stress and disease.