Transcript Document

Regeneration, Repair, and
Plasticity
Chapters 6, 7, 8, 10
P.S. Timiras
The Theories of Aging
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Decay of mitochondria
Cell senescence
Oxidative Stress
Shortening of telomeres
Evolutionary theories
• Disposable soma
• Antagonistic pleiotropy
• Mutation accumulation
• System theories
• Neuroendocrine
• Immune
• Rate of living
Neuroendocrine Theory
The Nervous System
Peripheral
Central
Autonomic
(whole-body innervation)
(brain, spinal cord)
(regulation of visceral
organs, tissues)
The Endocrine System
Pancreas: Insulin
GI hormones
Hypothalamus
Limbic system
Hypophysiotropic
hormones:
ADH
Oxytocin
Pituitary hormones:
Gonadotropins
Adrenal steroids
Thyroid hormones
Growth hormone
Prolactin
Brain Plasticity and
CNS Regenerative Potential
• From the beginning of the 20th Century until
the 1990s, it was stated that neurons DID NOT
proliferate.
• The fact that they COULD NOT proliferate did
not exclude the possibility of proliferation
under “specific conditions.”
• In fact, the CNS has a considerable
regenerative potential depending on the
special conditions of the neuronal
environment.
Neurons that may proliferate into
adulthood include:
• Progenitor “precursor” neurons lining the
cerebral ventricules
• Neurons in the hippocampus
• Neurons usually “dormant” with potential for
neuron and glia proliferation
• Neuroglia (astrocytes, oligodentrocytes) and
microglia (immune cells) with the ability to
perpetually self renew and produce the three
types of neural cells
Regenerative potential depends on
changes in whole body and neural
microenvironment
• Whole body changes:
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Physical exercise
Appropriate nutrition
Good circulation
Education
Stress
others
• Neural microenvironment
changes:
–Brain metabolism (oxygen
consumption, free radicals,
circulatory changes)
–Hormonal changes
(estrogens, growth factors,
others)
–others
Death Rates in 1986 among Persons 25- 64 Years Old in Selected
Education and Income Groups According to Race and Sex.
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Group
White
Men
Black
Women
Men
Women
deaths per 1000
Education- yr
Completed
School
0-11
12
College
1-3
4
7.6
4.3
3.4
2.5
4.3
2.8
2.1
1.8
5.0
6.0
3.2
2.2
Income-$
<9,000
9,000-14,999
15,000-18,999
19,000-24,999
>25,000
16.0
10.2
5.7
4.6
2.4
6.5
3.4
3.3
3.0
1.6
19.5
10.8
9.8
4.7
3.6
7.6
4.5
3.7
2.8
2.3
13.4
8.0
6.2
3.9
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Pappas, G., Queen, S., Hadden, W., and Fisher, G. The increasing disparity in mortality between socioeconomic groups in the United
States, 1960 and 1986. N. Engl. J Med. 329, 103-109, 1993.
Proportion of Remaining Life Expected to be Lived with a Disability in
Activities of Daily Living and Death Rates
________________________________________________________
At Age
65
At Age
75
At Age
85
Death Rates
per 1,000
White men
Low education
.11
Higher education .10
.21
.19
.45
.37
7.6
2.8
White women
Low education
.15
Higher education .14
.24
.23
.45
.40
3.4
1.8
Black men
Low education
.13
Higher education .11
.22
.18
.36
.31
13.4
6.0
Black women
Low education
.15
.22
.36
6.2
Higher education .14
.21
.31
2.2
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From: Guralink, J.M., et al., Educational status and active life expectancy among older blacks and whites, N Engl. J Med., July 8,
1993, Vol. 29:110-116
Mechanisms of Education Effects
Better access to medical care
Better access to recreational activity
Better nutrition
Higher income
Responsibility to health behaviors
No alcohol intake
No smoking
Increased brain reserve capacity?
More dendritic branching, cortical synapses?;
Better cerebral blood flow?;
Better neural cell efficiency, adaptability, redundancy, survival and growth
Fig. 7-4: “Denudation” of the neurons. Changes in
pyramidal neurons of the aging human cerebral cortex
Anatomical Correlates of Educational Protective Effects*
Educational Level
Anatomical Correlate
Increasing levels from <12 to >12
grades
total dendritic length
mean dendritic length
dendritic segment count
Location
Pyramidal cells in layer 2,3 of
Wernicke’s area
Variable Studied
Gender
Hemisphere
Education
Personal history
Hormonal Correlate
Thyroid Hormones
Glucocorticoids
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* From Jacobs et al., J Comp. Nuerol., 327, 97, 1993
dendritic number and length
reactive synaptogenesis