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Cell biology of normal brain aging: synaptic plasticity–cell death

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Abstract

Senescence of the brain seems to be related to increased levels of free oxygen radical (FOR). FOR may damage macromolecular compounds such as: proteins, lipids, and DNA. In the aging brain, increased FOR levels damage DNA, mitochondrial DNA (mtDNA), and nuclear DNA (nDNA). In DNA they damage single and double strands, leading to mutations in mtDNA and nDNA. Damage to mtDNA seems to result in decay of mitochondria, decreased production of ATP, and in the activation of the apoptotic process. In the aging brain, apoptosis does not seem to be activated in wild-type p53-expressing cells because the elevated levels of the p53 protein are no longer accompanied by decreased levels of the Bcl-2 protein and increased levels of the Bax protein. It seems that, in the aging brain, changes in the metabolism of neurons may lead to their decreased numbers in the cerebral and cerebellar cortex, hippocampus, basal nucleus of Meynert, locus ceruleus, and substantia nigra, as well as to decreased numbers of synapses and disturbed stimulation of synaptic plasticity in the senescent brain. Simultaneously, a decrease in neurogenesis in the aging brain may lead to a decline in the maintenance of tissue integrity, function, and regenerative response. Environmental enrichment and physical activity may improve hippocampal neurogenesis and induce neuronal plasticity. The morphological lesions in the senescent brain are undoubtedly followed by a disturbed balance between various types of neurons in the CNS. Nevertheless, the high plasticity of the CNS in humans most probably does not allow for the development of abnormalities in higher functions.

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The author wishes to acknowledge the help of Dr. Margarita Lianeri.

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  1. Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49, Przybyszewskiego St, 60-355, Poznan, Poland

    Jolanta Dorszewska

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Dorszewska, J. Cell biology of normal brain aging: synaptic plasticity–cell death. Aging Clin Exp Res 25, 25–34 (2013). https://doi.org/10.1007/s40520-013-0004-2

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