Aging brain - Definition and Overview

The human brain goes through several large-scale changes as the individual progresses from embryo through to old age.

Pre-natal development

Developmental neurobiology concerns itself with the development of the brain. The process of neurogenesis populates the brain, then programmed cell death cuts the growing brain down to size.

Adolescence

During adolescence the brain goes through a process of synaptic pruning.

Aging

Over the years, the human brain shows a decline in function and a change in gene expression. This modulation in gene expression may be due to oxidative DNA damage at promoter regions in the genome. Genes that are down-regulated over the age of 40 include:

• GluR1 AMPA receptor subunit
• NMDA R2A receptor subunit (involved in learning)
• Subunits of the GABA-A receptor
• Genes involved in long-term potentiation e.g. calmodulin 1 and CAM kinase II alpha.
• Calcium signalling genes
• Synaptic plasticity genes
• Synaptic vesicle release & recycling genes

Genes that are upregulated include:

• Genes associated with stress response and DNA repair
• Antioxidant defence

Normal aging is distinct from Neurodegenerative disease. DNA damage due to oxidation increase as the brain ages, possibly due to impaired mitochondrial function.

Further reading

• Lu et al 2004 - Gene regulation and DNA damage in the ageing human brain (http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v429/n6994/full/nature02661_fs.html)