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Systemic mechanism
- Involves complex regulatory mechanisms
- STRENGTH: CAN Account for differences among DIFFERENT species
- WEAKNESS: Difficulty accounting for varied mortality rates of SAME species
- 2 main Systemic theories include METABOLIC and GENETIC
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Metabolic Theory
- Systemic and INTRACELLULAR
- one of 2 main systemic theory
- Include 2 subtheories: 1. Rate-of-living Theory and 2. Mitochondrial damage Theory
- longevity INVERSELY related to metabolic rate
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Rate-of-living theory
- one of the Metabolic theories
- First suggested by Max Rubner & Pearl: showed metabolic rates correlated with longevity
- Newer evidence now contradicts Pearls' rate-of-living theory
- evidence from exercised vs. non-exercised animals (do not show any difference in MAXIMUM lifespan)
- oxygen consumption rates similar for all types of Dros, even if they have different lifespans
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Mitochondrial Damage theory
- one of the Metabolic Theories
- First suggested by Jaime Miguel: showed Vitamin E, which positive correlation with longevity in Dros., is in HIGH concentration in INNER-Mitochondrial Membrane
- Suggested Vit. E was protecting mitochondria from age-related damage
- Recent hypotheses from Wallace look at mitochondrial DNA as most likely Functional Target of Age-related damage
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Mitochondrial DNA as target of Age-related damage hypotheses
- 1. Rates of free radical damage to mitochondrial DNA are 10x GREATER vs. rates of damage to nuclear DNA
- 2. DNA repair rates in Mitochondria are SLOWER and LESS Accurate vs. nuclear DNA
- 3. Mitochondrial DNA deletions found to be associated with human pathologies, suggesting age-related deletions may have fxnal consequences.
- 4. Rates of unrepaired MITOCHONDRIAL DNA damage MORE correlated with SPECIES-specific lifespans vs. rates of unrepaired NUCLEAR DNA damage
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Genetic Theories
- Systemic and INTRACELLULAR
- one of 2 main systemic theory
- longevity from Particular set of genes
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Types of Genetic theories
- 1. Antioxidant defense enzymes
- 2. Energy, Stress and long life: antioxidant activity shown to correlate with low mortality rates in response to stressors such as toxicity, heat shock and desiccation
- 3. Protein synthesis fidelity: slowing of protein synthesis due to slowing of transcription or translation (specifically elongation). Can be prevented by calorie restriction
- 4. Calorie restriction: increases rate of transcription of catalase, superoxide dismutase and heat shock protein. Also contributes to Protein DEGRADATION
- 5. Telomeres: Strehler hypothesis loss of redundant genes (rRNA) contributed to aging. Have NO effect of senescence in Podospora
- 6. Signal transduction: decrease in cell membrane signaling
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Apoptosis Theory
- Systemic and INTRACELLULAR
- Failure of cells to undergo programmed is thought to cause diseases (cancer)
- due to inactivation of p53 gene
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Phagocytosis Theory
- Systemic, INTRACELLULAR
- Loss of Normal surface antigens MARKS them for DESTRUCTION by macrophages
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Neuroendocrine Theory
- Systemic, INTerCELLULAR
- Loss of negative-feedback homeostasis in neuroendocrine system
- Evidence comes from reproductive analysis in mammals
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Immunological Theory
- Systemic, INTerCELLULAR
- Loss of immune regulation
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Systemic, INTRACELLULAR theories
- Metabolic
- Genetic
- Apoptosis
- Phagocytosis
- Neuroendocrine and Immunological Theories are Systemic, BUT INTercellular
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