Sixty years old is the breakpoint of human frontal cortex aging

Abstract

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.

R.C. received predoctoral fellowships from the Autonomous Government of Catalonia. We thank T. Yohannan for editorial help. Research reported in this publication was supported by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (FIS Grants PI14/00757 and PI14/00328), and the Autonomous Government of Catalonia (2014SGR69 and 2014SGR168) to I.F. and R.P. This study was co-financed by FEDER funds from the European Union (‘a way to build Europe’).