TABLE 1.
Summary of the aging process in the brain.
| Gross changes | Microscopic changes | |
| Structural Aging | ||
| ● Volume loss | ● Lipofuscin accumulation | |
| ● Neurodegeneration in the GM, Demyelination in the WM, Ventricular enlargement | ● Neurofibrillary tangles, amyloid plaque formation | |
| ● Sulci widening | ● Dendritic tree decrease, axon number decreases, demyelination | |
| ● Cerebrovascular diseases | ||
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| Acetylcholine | Monoamine | Neurosteroid |
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| Biochemical and Metabolic Aging | ||
| ● Dysfunction in the cholinergic system: memory decline | ● Disturbed dopaminergic pathway | ● Decreased testosterone disturbs BBB, and invoke inflammation activity |
| ● Nicotinic binding ability lost | ● Disturbed serotonergic pathway | ● Decreased androgen and estrogen reduce receptor expression and synapse density. |
| ● Nicotinic acetylcholine receptors decrease | ● Decreased receptors and binding ability | |
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| Changes in the nucleus | Mitochondrial dysfunction |
Accumulation of oxidatively damaged molecules |
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| Cellular and Molecular aging | ||
| ● Alteration in gene expression | ● mtDNA damage | ● ETC damage |
| ● Decrease in synaptic function | ● Disturbed ATP production | ● Lipid, protein DNA/RNA damage |
| ● Increase in stress responses | ● Apoptosis induced | ● Disturb cellular metabolic pathway or homeostasis |
| ● Telomere shortening | ||
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| Impaired lysosome and proteosome function |
Electrophysiological Changes in the Brain by Aging |
Dysregulation of neuronal calcium homeostasis |
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| ● Autophagy and UPS reduction ● Increase cellular wastes |
● AP threshold changes: changes in voltage-gated Na+ channel activation prperties and subtypes expression pattern. ● AP amplitude decrease. ● AP axonal conduction rate decrease |
● Plasma membrane proteins: - Decreased NMDAR function - Post-translational alterations in receptors - Increased VDCC number ● Changes in Ca2+ influx and disturb cellular Ca2+homeostasis - Cellular organelles - Mitochondria : Depolarization disturbs electrochemical gradients - ER : Ca2+regulating receptors changes. : Changes in calcium-binding protein : Decreased expression and disturbs Ca2+buffering |
GM, gray matter; WM, white matter; BBB, brain blood barrier; mtDNA, mitochondrial DNA; ETC, electron transport complex; UPS, ubiquitin proteasome system; AP, action potential; NMDAR, N-methyl-D-aspartate receptor; VDCC, voltage-dependent calcium channel; ER, endoplasmic reticulum; ATP, adenosine triphosphate.