AGEING AND THE

BRAIN

Bethy S. Hernowo
NBSS TWP
 Introduction
For many people approaching old age ,
deteriorating brain function is the aspect of
growing old that they most fear.
Some peoples brains age much better than others.
Why this might be?
How more of us can improve the chances of
preserving our brains as they age?
What changes occur in human brains with
ageing?
 Ageing of the human brain
Brain changes with ageing
First, young brains in develop world larger and
heavier by about 1gr/year.
Second, the number of very elderly brains examined
has been relatively low until recently.
Third, diseases that cause a reduction in brain
weight and volume are increase
Fourth, by brain imaging , the longitudinal measures
on the same brain have been possible to study
 Macroscopic brain changes with
age
Age 20-60 years, loss of brain weight 0.1% per
year , more rapid loss thereafter.
Weight remain stable until the age of 50 years
then progressively decrease.
Brain volume found to decrease with age.
Diffuse in white matter and some regional
differences in grey matter.Frontal and parietal
more affected than temporal and occipital cortex
 Cont
Brain volume reduction increase 0.1-
0.2%/year at age 30-50 years to 0.3-
0.5%/year at age >70 years.
Ventricular system expands, leptomenings
thicker slightly with age and subarachnoid
enlarges.
Microscopic brain changes with age

Loss of neurons occurs with age (10-60%)

Cerebral cortex, hypocampus, cerebral Purkinye
cells also affected except cranial nerve nuclei
Amyloid plaque and neurofibrillary tangles
formation in elderly brains over the age of 80
years.
30% reduction in neurons at dorsolateral
prefrontal cortex correlates with impairment on a
working memory task
 Cont
Neuron size decrease with age particularly
in cerebral cortex.
Neuron size is thought to reflect the extent
of the dendritic and axonal arborizations of
the cells.
Synapses reduction (46%) in spine number
and density in human over 50 years of age.
 Other microscopic alteration
Increase number of corpora amylacea around
blood vessel or close to pial or ependymal
surface or astrocyte processes.
Increase the amount of iron that can facilitate
oxidative stress.
Increase the amount of advance glycation end
products.
Increase the number and size of astrocytes and
microglya.
 Cont
Increase in the lipofuscin content of
neurons.
It tends to accumulate in large cortical and
thalamic neurons, inferior olive neurons
and motor neurons than in others.
Lipofuscins consist of material derived
from lysosomal degradation.
Cellular and molecular changes
High energy demands of neuron render
them vulnerable to ageing.
Oxygen free radicals, have the capacity to
damage proteins, nucleic acids and lipids.
DNA damage leads to reduced gene
expression. 4% of the 11000 genes studied
reduced expression after the age of 40 years.
Production s of advanced glycation end
products (AGEs).
 Cont.
Calcium dysregulation
Decreasing mitochondrial efficiency with
ageing increasing oxidative stress
Eleveted levels of intracellular Ca 2+
activated calcium proteases (caspases)
damaging effect of cells cell death by
apoptosis
 Cont..
Genes that influence brain ageing
Apolipoprotein E ( ApoE) gene
ApoE e2 is protective against AD and e4 is
risk factor for late onset of AD
Prion protein gene (PRNP)
PRNP play a role in protecting neurons from
the effect of cellular stress
Environmental factors and brain ageing

Diet deleterious effect on brain

metabolism
Calorie intake cholesterol and BP
Blood homocysteine risk factor for AD
and CVD
Beneficial influence on brain function :
Physical exercise, extended education,
cognitive stimulation, high intake of
polyunsaturated fatty acid and vitamins
 Cont
The influence of toxins in causing brain
damage :
Pesticide rotenone and the herbicide paraquat
in PD
 Conclusions
The brain undergoes subtle but definite decline in
structure and function with age .
This condition prove to be reversible because of :
Neurogenesis can persist into adulthood
Protective neurotrophic factor production can be
enhanced under certain conditions ( exercise, diet) and
Oxidative damage to the brain can be influenced by
diet and other lifestyle factors.
Ref: J Pathol 2007;211:181-187.
www.interscience.wiley.com/thejournalofpathology