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Theoretical Gerontological approach
Darwinian terms: disposable soma theory
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Empirical Aging studies
Stochastic and Systemic
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Arking's Theories of aging
- 1. stochastic
- 2. systemic
- 3. intracellular
- 4. intercellular
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Stochastic mechanism
- ie: wear-and-tear theory
- STRENGTH: CAN account for differences WITHIN SAME species
- WEAKNESS: explaining wide range of mortality among DIFFERENT species (ie two types of mice)
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Intracellular Theory
- Major aging done WITHIN the cell
- DO NOT account for extracellular processes, wuch as glucose derived collagen
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Intercellular Theory
- Originate OUTSIDE of the cell
- CANNOT explain SINGLE cell organisms
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Which theories are STOCHASTIC, INTRACELLULAR theories
- Altered Protein
- Somatic mutation
- DNA damage and Repair
- Error catastrophe
- Dysdifferentiation
- Oxidative damage
- But, Posttranslational Protein Modification Theory is STOCHASTIC, INTercellular
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Altered Protein Theory
- STOCHASTIC, INTRACELLULAR
- Proteins undergo CONFORMATIONAL changes to ALTER function
- First proposed by ROTHSTEIN
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Somatic mutation Theory
- STOCHASTIC, INTRACELLULAR
- Altered DNA mutations that CAN be inherited
- Accumulate overtime in somatic cells, leading to EVENTUAL DEATH
- Leo Szilard first proposed this
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DNA damage and Repair theory
- STOCHASTIC, INTRACELLULAR
- Altered DNA mutations that CANNOT be inherited
- Cells DO NOT recognize these mutations as DNA damage
- ie: p53 tumor suppressor gene
- Sonneborn, Bernstein and Ames showed DNA damage in different organisms
- evidence against this is theoretical and argues that these theories only look at lifespan, NOT mortality rates
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Error Catastrophe Theory
- STOCHASTIC, INTRACELLULAR
- Altered Amino acid sequences in proteins May cause POSITIVE feedback loop leading to DEATH of cell
- Orgel first proposed this
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Dysdifferentiation Theory
- STOCHASTIC, INTRACELLULAR
- Inappropriate protein synthesis in aging differentiated cells
- Richard Cutler first proposed
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Oxidative Damage Theory
- STOCHASTIC, INTRACELLULAR
- STRONGEST stochastic theory
- Denham Harman first proposed: free radical theory
- Vit E and C important Antioxidants as well as MELATONIN
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Free radical theory biomarker studies
- Oxidative damage and anti-oxidant gene activity Increase in Dros: in short lived strains there is HIGH oxidative damage, and LOW anti-oxidant activity
- Lippofuscin accumulation is REDUCED in animals given Vit. E supplements
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Vitamin E
Found in inner leaflet of innermitochondrial membrane
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Vitamin C
Found in Highest concentration in cell cytosol
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Waste Accumulation Theory
- STOCHASTIC, INTRACELLULAR
- Failure of cells to REMOVE waste products (such as LIPOFUSCIN) resulting in BUILDUP of toxins
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Wear-And-Tear Theory
- Traditional explanation of aging (STOCHASTIC)
- Favored by Aristotle, Maimonides, Bacon and Weismann
- Molecularly this is correct, but mostly from intrinsic factors, not envir.
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Posttranslational Protein Modification Theory
- STOCHASTIC, INTerCELLULAR
- Structural changes to EXTRACELLULAR proteins lead to age related pathologies
- Bjorksten first suggested the CROSSLINKAGE of extracellular molecules
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Steps for glycation of collage
- from Posttranslational protein mod. theory
- 1. glucose attaches to lysine
- 2. Schiff base converted to Amadori product (IRREVERSIBLE)
- 3. Amadori product attaches to the 2nd lysine
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