Healthy brain aging: Interplay between reactive species, inflammation and energy supply

Brains' high energy expenditure with preferable utilization of glucose and ketone bodies, defines the specific features of its energy homeostasis. The extensive oxidative metabolism is accompanied by a concomitant generation of high amounts of reactive oxygen, nitrogen, and carbonyl species, which will be here collectively referred to as RONCS. Such metabolism in combination with high content of polyunsaturated fatty acids creates specific problems in maintaining brains' redox homeostasis. While the levels of products of interaction between RONCS and cellular components increase slowly during the first two trimesters of individuals' life, their increase is substantially accelerated towards the end of life. Here we review the main mechanisms controlling the redox homeostasis of the mammalian brain, their age-dependencies as well as their adaptive potential, which might turn out to be much higher than initially assumed. According to recent data, the organism seems to respond to the enhancement of aging-related toxicity by forming a new homeostatic set point. Therefore, further research will focus on understanding the properties of the new set point(s), the general nature of this phenomenon and will explore the limits of brains' adaptivity.