Figure 2.

Relationship between ageing and neurodegeneration. The process of ageing (top panel) can be seen as a continuous decrease of the homeostatic reserve, defined as the capacity of cells to fight various metabolic stressors and maintain the cells/organ on the steady-state level of homeostasis. With age, acute surges of metabolic activity become more dangerous as they reach the limits of homeostatic reserve defences, a process that underlies the age-dependent increased in vulnerability. When the homeostasis line intersects the homeostatic reserve line, the biological system becomes unstable and severe dysfunction/death ensues. The process of neurodegeneration, characterized by extensive neuronal death, becomes mostly manifest at the older ages, on the background of decreased homeostatic reserve, and could result either from (a) an increased level of metabolic load or from (b) an accelerated reduction of the homeostatic reserve or from a combination of both.