Keeping the Wolf from the Door: Life History Responses of Mammals to Living in an Energy Limited World

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Aging in Natural Populations Of Mammals
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Why and how do mammals get old and die? How is
this affected by a. Reproduction b. Natural
Stressors (competition, predators, etc.) c.
Maternal and Cohort Effects
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Senescence

• the process of decline in physiological
  functioning that results in increasing mortality
  rates with increasing age after some point in the
  lifespan

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Theory of Senescence
1. The age at which senescence is first
expressed depends on how much mortality
occurs independent of the effects of
senescence. 2. Senescence should not be
expressed until after the age at first
reproduction.
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Disposable Soma Hypothesis
Total Energy Reserve
Total Energy Reserve
Trade-offs
Somatic Maintenance
Reproduction
Maximizing Fitness
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Disposable Soma Hypothesis
High extrinsic mortality
Reproduction
Reproduction
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Disposable Soma Hypothesis
Low extrinsic mortality
Somatic Maintenance
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Principal Research Approach

• Target the
• STRESS AXIS -
• a crucial system for survival, allows animals to
  cope with challenges, and deteriorates with age.

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Stress

• Stress Response - the set of responses by birds
  and mammals by the stress axis to potentially
  harmful environmental challenges

• Stressor - anything that upsets the
• homeostatic balance within an animal
• Environmental
• Physical
• Psychological

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Response to Stressor is Crucial and Changes with
Age, Condition, Experience, etc.

• Crucial components
• Response to the stressor - how rapid is it and
  how intense?
• Negative Feedback - how rapidly is it terminated?

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Negative Feedback
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Hypothalamic-pituitary-adrenal Axis
Importance of the HPA Axis

• Role in somatic maintenance

HPA Axis
Reproduction
Stress
Metabolism
Immunity

• Crucial to organisms ability to deal with stress

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GR
Hippocampus
M
R


PVN
Hypothalamus
AVP
CRH
Anterior
Pituitary
ACTH
Adrenal
Cortex
Glucocorticoids
Mobilization Of Energy
Immuno- suppression
Suppression Of Growth
Suppression Of Digestion
Reproductive Suppression
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Stress Response
Good if short term Acute Response Classic
Flight or Fight Response Bad if long term
Chronic Response short term effects are
prolonged, with potential permanent
consequences - Brain changes,etc.
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LIVER
Cortisol has both these effects
GLUCOSE
GLUCONEOGENESIS
GLYCOGEN
ENERGY
SUPPLY
MUSCLE
FATTY
GLYCEROL
AMINO
GLUCOSE
ACIDS
ACIDS
LYMPHOID
SKIN
CONNECTIVE
ADIPOSE
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Methods to study stress response in Natural
Populations

• Before and After assessment (crude)

• Measurement in feces and urine (noninvasive,
  need rigor)

• Challenge Protocol
• Capture
• Hormonal

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ACTH Stimulation Test

• Inject ACTH
• Measure glucocorticoid levels
• Moderate increase is normal
• Excessive increase or reduced
• response (species dependent) indicative of
  chronic stress.

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Hormonal Challenge Protocol
Units
Time
0
30
60
120
BASE Bleed ACTH Injection
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HIPPOCAMPUS
ACTH
HYPOTHALAMUS
CRF
PITUITARY
ACTH
ACTH
ADRENALS
Cortisol / Corticosterone
BLOOD
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HIPPOCAMPUS
ACTH
HYPOTHALAMUS
CRF
PITUITARY
ACTH
ACTH
ADRENALS
Cortisol / Corticosterone
BLOOD
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Poor Condition
Free Cortisol
Good Condition
Time
ACTH
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Hormonal Challenge Protocol Progress to date

• - Carried out Challenge on 100 red squirrels
• 50 in 2003 on Lloyd
• 49 in 2004 on Kloo and Sulphur
• Data from 2004 best as exact ages of animals
  known
• (oldest 6 yrs old, 1998 about 11 or more)
• Blood Component Analysis
• Glucose Done
• Blood Hematolgy Done
• Free Fatty Acids and Albumin Pending
• Hormone Analysis - Cortisol - Pending
• Statistical Analysis - Pending

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Stress Response is not Static

1. May be modulated over annual cycle to optimize
   reproduction, survival, or both
2. Modified during development Programming of the
   Brain.
3. Modified by experience and AGE.

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Changes in the HPA with AGE
Either Age-Dependent Declines occur resulting in
death Or No change can be observed as Axis too
critical for any margin of error
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Glucocorticoid Receptor Regulation
Hippocampus
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GR
MR
CRH mRNA AVP mRNA
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Hypothalamic PVN
CRH
AVP
POMC mRNA
Anterior Pituitary
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POMC
ACTH
Adrenal Cortex
Cortisol
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Hippocampus
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The rodent hippocampus
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In Situ Hybridization
MR mRNA probe
GR mRNA probe
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1997 1998
1999
Increase
Peak
2000 2001
GR mRNA in situ images In snowshoe Hares
Decline
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• Age-dependent changes in
• brain organization
• collected 23 in 2003
• 39 in 2004
• critical need to age accurately
• using sectioning femurs.

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Time Frame hormone and brain sectioning and in
situhybridization by June-July
2005. Papers Papers on Age-dependent changes in
HPA axis a. hormonal changes b. Brain
changes Other Papers Territory Quality -
Physiology Correlates. Relationship to
reproduction and survival
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• Future Studies
• Individual variation and Quality
• use of noninvasive fecal analysis
• to make various comparisons
• amongst males, females, juvs
• Feeding Experiment -
• - use of blood sampling, stress tests
• and/or fecal analysis to compare
• squirrels on different treatments
• Need to assess first how good blood data
• already obtained predict or are related to
• Behavior, terrtory quality, etc.