Middle aged turn point in parameters of oxidative stress and glucose catabolism in mouse cerebellum during lifespan: minor effects of every-other-day fasting

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

“…In our studies, this explanation worked fine when comparing oxidative stress parameters between young and middle-aged mice [ 24 , 25 ], but did not explain why similar data were obtained in middle-aged and old mice. Despite the general belief that the intensity of oxidative stress is enhanced during aging, the data on the oxidative state of the cysteome (or redoxome) during lifespan are contradictive [ 72 , 73 , 74 ].…”

“…Despite an intensive oxidative metabolism, no highly efficient brain-specific ROS defense systems were described so far. Surprisingly, however, the levels of ROS-mediated lipid/protein oxidation products in the brain are comparable to those found in other organs [ 25 , 68 ].…”

“…Interestingly, virtually no differences in age-related changes were found between males and females. Since age-related profiles may differ for different markers of oxidative stress [ 3 , 4 ], when comparing the aged group with the younger cohort [ 24 , 25 ] the results obtained depend on at least two conditions: (1) the relative age of the younger group and (2) the nature of parameters under study.…”

“…This redistribution of the glucose intermediate fluxes between glycolysis and PPP may represent an efficient mechanism to strengthen the antioxidant defense and to prevent further intensification of oxidative stress. In our recent work, we have disclosed some molecular mechanisms underlying such changes [ 24 , 25 ]. In both, cortex and cerebellum, the activities of key glycolytic enzymes PFK and PK were lower in middle-aged and old mice relative to young ones ( Figure 3 ).…”

“…The brain is especially prone to ROS-mediated toxicity for several reasons: (i) the intense oxidative metabolism, (ii) the high levels of polyunsaturated fatty acids, serving as primary substrates for ROS-promoted oxidation and (iii) a rather high number of resident immune cells [ 20 ]. Recently, we discovered that crucial changes in the functional properties of microglia, the brain’s resident immune cells, as well as the energy and redox metabolisms, occur already at middle age [ 4 , 21 , 22 , 23 , 24 , 25 ]. Here, we discuss the interplay between the energy and redox metabolism of the brain and its immune system along the lifespan and focus on middle age as a critical point for the reorganization of energy and redox homeostasis as well as the operation of the brain’s immune system.…”