Aging in Natural Populations Of Mammals
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Transcript of Aging in Natural Populations Of Mammals
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Aging in Natural PopulationsOf Mammals
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Why and how do mammals get old and die?How is this affected by:a. Reproductionb. 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 SenescenceTheory of Senescence
1. The age at which senescence is first expressed1. The age at which senescence is first expresseddepends on how much mortality occursdepends on how much mortality occursindependent of the effects of senescence.independent of the effects of senescence.
2. Senescence should not be expressed until2. Senescence should not be expressed untilafter the age at first reproduction.after the age at first reproduction.
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Reproduction
SomaticMaintenance
Disposable Soma Hypothesis
Total EnergyReserve
Trade-offs
SomaticMaintenance
Reproduction
MaximizingFitness
Reproduction Somatic Maintenance
TotalEnergy Reserve
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Reproduction
Disposable Soma Hypothesis
High extrinsic mortality
Reproduction
SomaticMaintenance
DECREASEDLIFESPAN
Reproduction
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Reproduction
SomaticMaintenance
Disposable Soma Hypothesis
Low extrinsic mortality
INCREASEDLIFESPAN
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 Stress Response - the set of responses by birds and mammals by responses by birds and mammals by the stress axis to potentially harmful the stress axis to potentially harmful environmental challengesenvironmental challenges
Stressor - anything that upsets the Stressor - anything that upsets the
homeostatic balance within an animalhomeostatic balance within an animal EnvironmentalEnvironmental Physical Physical PsychologicalPsychological
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Response to Stressor is Crucial and Changes with Age,
Condition, Experience, etc.
Crucial components:Crucial components:
1.1. Response to the stressor - Response to the stressor - how rapid is it and how how rapid is it and how intense?intense?
2.2. Negative Feedback - how Negative Feedback - how rapidly is it terminated?rapidly is it terminated?
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PITUITARYPITUITARY
ADRENALSADRENALS
HIPPOCAMPUSHIPPOCAMPUS
BLOODBLOOD
HYPOTHALAMUSHYPOTHALAMUS
ACTH
CRFCRFCRFCRF
ACTHACTHACTHACTH
CortisolCortisolCortisolCortisol
STRESSSTRESS
NegativeNegativeFeedbackFeedback
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Hypothalamic-pituitary-adrenal Axis
Importance of the HPA Axis
• Role in somatic maintenance
• Crucial to organism’s ability to deal with stress
HPA Axis
Reproduction
Immunity Metabolism
Stress
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Hippocampus
Hypothalamus
AnteriorPituitary
GR
MR
AdrenalCortex
MobilizationOf Energy
SuppressionOf Growth
Immuno-suppression
SuppressionOf DigestionReproductive
Suppression
ACTH
Glucocorticoids
AVPCRH
PVN
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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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CATABOLICCATABOLIC
ANABOLICANABOLIC
LIVER
GLUCONEOGENESIS GLUCOSE
GLYCOGEN
MUSCLE
LYMPHOID
SKIN
ADIPOSE
ENERGYSUPPLY
FATTYACIDS
GLYCEROLGLUCOSE
CONNECTIVE
AMINOACIDS
Cortisol has both these effects:
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Methods to study stress response in Natural
Populations Before and After assessment (crude) Before and After assessment (crude)
Measurement in feces and urine Measurement in feces and urine (noninvasive, need rigor)(noninvasive, need rigor)
Challenge ProtocolChallenge Protocol CaptureCapture HormonalHormonal
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ACTH Stimulation Test
Inject ACTHInject ACTH Measure glucocorticoid levelsMeasure glucocorticoid levels
Moderate increase is normalModerate increase is normal
Excessive increase or reduced Excessive increase or reduced
response (species response (species dependent) dependent) indicative of chronic indicative of chronic stress. stress.
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Hormonal Challenge Hormonal Challenge ProtocolProtocol
00 3030 6060 120120
BASE BleedBASE BleedACTH InjectionACTH Injection
ACTH ACTH BleedsBleeds
UnitsUnits
TimeTime
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PITUITARYPITUITARY
ADRENALSADRENALS
HIPPOCAMPUSHIPPOCAMPUS
BLOODBLOOD
HYPOTHALAMUSHYPOTHALAMUS
ACTH
CRFCRFCRFCRF
ACTHACTHACTHACTH
Cortisol / Cortisol / CorticosteroneCorticosterone
Cortisol / Cortisol / CorticosteroneCorticosterone
ACTHACTH
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PITUITARYPITUITARY
ADRENALSADRENALS
HIPPOCAMPUSHIPPOCAMPUS
BLOODBLOOD
HYPOTHALAMUSHYPOTHALAMUS
ACTH
CRFCRFCRFCRF
ACTHACTHACTHACTH
Cortisol / Cortisol / CorticosteroneCorticosterone
Cortisol / Cortisol / CorticosteroneCorticosterone
ACTHACTH
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Poor ConditionPoor Condition
Good ConditionGood Condition
ACTHACTH
Free Free CortisolCortisol
Time
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Hormonal Challenge ProtocolHormonal Challenge ProtocolProgress to date:Progress to date:
- Carried out Challenge on 100 red squirrels50 in 2003 on Lloyd49 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 Declinesoccur resulting in deathOrNo change can be observed asAxis too critical for any marginof error
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Glucocorticoid Receptor Regulation
ACTH
Cortisol
CRH mRNAAVP mRNA
Hippocampus
_
_
_
HypothalamicPVN
AnteriorPituitary
AdrenalCortex
POMC mRNA
POMC
CRH
AVP
GR
MR
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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
CA 1/2
CA 3DG
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1997& 1998 1999
2000 & 2001
GR mRNA GR mRNA in situ imagesin situ imagesIn snowshoeIn snowshoeHaresHares
Increase Peak
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 changesb. Brain changes
Other Papers: Territory Quality - Physiology Correlates. Relationship to reproduction and survival
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Future Studies1.Individual variation and Quality
- use of noninvasive fecal analysisto make various comparisonsamongst males, females, juvs
2.Feeding Experiment -- use of blood sampling, stress tests
and/or fecal analysis to comparesquirrels on different treatments
Need to assess first how good blood dataalready obtained predict or are related toBehavior, terrtory quality, etc.