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15 Cards in this Set
- Front
- Back
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Destructive agents
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1. UV radiation
2. Free Radicals (FRs)=ROS |
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OH
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Hydroxyl radical -> long lived, goes deep into cells
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O2-
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Superoxide radical short lived membrane damage
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OONO
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Peroxynitrite - forms very fast
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Tyrosine + NO + OONO-
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Nitrotyrosine; common in diseased tissues
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H2O2
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Hydrogen peroxide - not a FR but has an unpaired electron
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Formation of free radicals
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Ionizing radiation
Smoking Air pollution Inflammation Metabolism All equal DNA damage |
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Free radical damage
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DNA - Increases likelihood of mutations
Proteins - Induce cross linking by oxidising individual amino - acids (same for extracellular proteins such as collagen) Lipids - peroxidation leading formation of aldehydes |
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Naked mole rat
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Lives up to 31 years (much more than other rodent)
highly resistant to cancer and maintain vascular function longer Plasma membranes have much less DHA (docosahexanoic acid) and Phosphatidylchlines/ Phosphatidylserines |
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Antioxidants
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Not destabilised by electron donation
Enzymes: Glutathione peroxidase, superoxide dismutase (SOD) Micronutrients:Vitamins E, C, β-carotene, lycopene, α-lipoic acid Others: Selenium, Oestrogen, Reveratrol, Curcumin oil, N-Acetyl-cysteine |
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Oxidative Stress
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An increase in FR production coupled with a shortfall in available anti-oxidants causing:
-Increased anti-oxidative enzyme production, Production of chaperonins (HSPs), Expression of immediate early genes (IEGs), expression of DNA repair enzymes and expression of apoptosis-related proteins. BUT aged cells are less able to respond in these ways |
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Cell senescence
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Dipolid cells cease to divide. 'replicative senescence'
Senescent fibroblasts also contain lipofuscin and produce more collagenase and less TIMPS Senescent endothelial cells produce interleukin 1 leading to inflammation |
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Telomerase
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A specialised reverse transcription
hTERT is the part of the enzyme that synthesises the TTAAGG repeats - cells become immortalised |
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Genetic Instability
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1. Gene repression during ageing
2. Altered gene expression during ageing 3. DNA damage during ageing Nuclear DNA is inherently unstable |
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DNA damage that can be induced by FRs
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1. Point mutations - single bases
2. Translocation from one chromosome to another 3. Inversions 4. Single stranded DNA breaks 5. DNA stranded DNA breaks 6. Deletion of while genes 7. Insertion of viral DNA |
