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Abstract
Aging is believed to be the result of alterations of protein expression and accumulation of changes in biomolecules. Although there are numerous reports demonstrating changes in protein expression in brain during aging, only few of them describe global changes at the protein level. Here, we present the deepest quantitative proteomic analysis of three brain regions, hippocampus, cortex and cerebellum, in mice aged 1 or 12 months, using the total protein approach technique. In all the brain regions, both in young and middle-aged animals, we quantitatively measured over 5,200 proteins. We found that although the total protein expression in middle-aged brain structures is practically unaffected by aging, there are significant differences between young and middle-aged mice in the expression of some receptors and signaling cascade proteins proven to be significant for learning and memory formation. Our analysis demonstrates that the hippocampus is the most variable structure during natural aging and that the first symptoms of weakening of neuronal plasticity may be observed on protein level in middle-aged animals.
Highlights
Aging is associated with general decline in cognitive functions [1]
We found that the total protein expression in middle‐aged brain structures is practically unaffected by aging, there are significant differences between young and middle‐aged mice in the expression of some receptors and signaling cascade proteins proven to be significant for learning and memory formation
Our analysis demonstrates that hippocampus is the most variable structure during natural aging and that in middle-aged animals, the machinery involved in the formation of various forms of hippocampal neuronal plasticity is significantly altered
Summary
Aging is associated with general decline in cognitive functions [1]. The technique used by Walther and Mann to study differences between young adult (5 months) and old (26 months) rats has revealed a relative stability of brain structures proteomes during aging [7]. More recent proteomic studies on age-associated changes in various brain structures, e.g. on aging of human and mice hippocampus [10,11], are roughly in line with the results of Walther and Mann, they have demonstrated significant changes in titers of enzymes catalyzing regulatory reactions in energy metabolism which is reflected by basically different organization of www.aging‐us.com astrocyte-neuron crosstalk in young and old hippocampus [11]. One of the most recent quantitative study on aging of human brain structures [12] has presented data from a very small group which makes the data hard to interpret
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