No abstract

The human brain is a target of the aging process like other cell systems of the human body. Specific regions of the human brain exhibit differential vulnerabilities to the aging process. Yet the underlying mechanisms that sustain the preservation or deterioration of neurons and cerebral functions are unknown. In this review, we focus attention on the role of lipids and the importance of the cross-regionally different vulnerabilities in human brain aging. In particular, we first consider a brief approach to the lipidomics of human brain, the relationship between lipids and lipoxidative damage, the role of lipids in human brain aging, and the specific targets of lipoxidative damage in human brain and during aging. It is proposed that the restricted set of modified proteins and the functional categories involved may be considered putative collaborative factors contributing to neuronal aging, and that mitochondrial ATP synthase is a key lipoxidative target in human brain aging.

Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional throughout a healthy adult lifespan, yet the mechanisms that maintain function and protect against neurodegenerative processes during aging are unknown. Here we show that protein oxidative and glycoxidative damage significantly increases during human brain aging, with a breakpoint at 60 years old. This trajectory is coincident with a decrease in the content of the mitochondrial respiratory chain complex I-IV. We suggest that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function.