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Biochem Block 5

Endocrine theory Biological clocks act with hormones to control the pace of aging. Aging decreases production of hormones like estrogen, testosterone, dehydroepiandrosterone, GH and melatonin Correlates with decrease in many physiological mechanisms
Immunological theory Programmed decline in immune system functions leading to infectious disease and thus aging and death
Wear & tear Cells/tissues have vital parts that wear out
Rate of living Lifespan is inversely proportional to organism’s rate of O2-based metabolism
Cross-linking Body processes are slowed by accumulation of cross-linked proteins that damage cells/tissues
Disposable soma ______ _____ somatic cells are maintained only to ensure continued breeding success – after reproduction, the soma is disposable (= life span theory)
Mutation accumulation mutations that adversely affect health at older ages are not selected against
Replicative Senescence Occurs at the cellular level Cells cease to divide, but continue to respond to hormones and other stimuli until they die.
Hayflick Limit No. of times cells can divide before they reach Replicative Senescence[RS] (in vitro)
Brain cells ______cells are a good example – reach Replicative Senescence after just a few divisions
Hayflick Limit The higher the _______ in the cells of an organism, the longer the lifespan.
Cancer cells ______cells are immortal and have no Hayflick Limit.
Dying, phenotype Cells that reach Replicative Senescence [RS] are more resistant to_____ and have a different ______.
fibroblasts Senescent _______may cause cancer by secreting enzymes that degrade extra-cellular matrix.
Telomeres _____may hold the clue to understanding Replicative Senescence [RS]
Telomerase Special enzyme which functions to repair telomeres by extending them. A protein with an RNA molecule. Works in association with DNA polymerase. Adds repeating frames (TTAGGG) to overhanging strand – DNA polymerase adds complementary strand
protective loop In the third action of telomerase an Extension continues and proteins attach and curl chromosome end into a ______ ______.
Dyskeratosis congenita [disorder]Only one functional telomerase gene. Telomeres shorten rapidly. Age prematurely – grey hair in teens etc. Die in early adulthood from bone marrow failure and inability to fight infections.
Telomeres Patients with Dyskeratosis congenital the ________shorten rapidly. Age prematurely – grey hair in teens etc. Die in early adulthood from bone marrow failure and inability to fight infections.
cellular senescence, cross-linking Georgia’s opossums on sapelo island used as an example to show that due to their lack of predators they had Reduced_____ ______. and Reduced levels of collagen _______-_______
Codon restriction Fidelity/accuracy of mRNA translation becomes impaired
Error catastrophe Fidelity of gene expression declines – results in increased fraction of abnormal proteins
Somatic mutation Accumulation of molecular damage to genetic material
Dysdifferentiation Gradual accumulation of random molecular damage impairs regulation of gene expression
Gene regulation Aging is caused by changes in gene expression regulating both development and aging
faster Mitochondrial DNA gets damaged____ than nuclear DNA
progeroid syndromes Familial accelerated aging disorders
Hutchinson-Gilford [HG] progeroid syndrome there is a problem with the LMNA gene, which codes for lamin A protein. Some animal models result from abnormal mitochondria or abnormal signal transduction.
lamin A Dysfunctional ______causes mislocalization of heterochromatin, nuclear blebbing and misregulation of gene expression
Wiedemann – Rautenstranch syndrome also known as neonatal progeroid syndrome, very rare genetic disorder characterized by an aged appearance at birth, growth delays before and after birth, deficiency or absence of the layer of fat under the skin . decreased life expectancy.
advanced glycation products (AGE’s) Glycoxidation – glucose + oxidation = ______ ______ ______ inflammation
Apoptosis Programmed cell death results from intrinsic damage and genetically determined events
Cellular senescence Stress-related, but similar to replicative senescence in that the phenotypes of aging are caused by an increase in senescent cells
Free Radical Theory of Aging Theory that Oxygen free radicals generated as a by-product of oxidative metabolism cause cumulative damage: Structural degeneration, Apoptosis, Functional decline, Age-related diseases
free radicals Atom or an atom in a molecule that has an unpaired electron. These are usually very reactive and will steal electrons
Homolytic fission _____ ______of a covalent bond will produce a pair of free radicals
Propagation Three phases of radical reactions: [1]Initiation, [2]______,[3]Termination
melanin An example of a Persistent radical is ____ which persists for 106 years
vitamin E An example of a Stable radical is_____ which is a conjugated π system
CoQ ____generates superoxide in mitochondria
superoxide CoQ generates _____in mitochondria
H2O2 _______permeates membranes easily and can enter all organelles
3.5 ml/kg/min At rest, oxygen usage is ____ ml/kg/min
P-450 Cytochrome ____ enzymes are a major source of free radicals “leaked” from reactions
P-450 enzymes Induction of _____ by alcohol, drugs, or chemical toxicants leads to increased cellular injury
Xanthine oxidase an enzyme in purine degradation that can reduce oxygen to O2.- or H2O2 in the cytosol, is thought to be a major contributor to ischemia-reperfusion injury, especially in intestinal mucosal and endothelial cells
Hydroxyl, hydrogen radicals Ionizing radiation has a high enough energy level that it can split water into the _____and____ _____, thus leading to radiation damage of the skin, mutations, cancer and cell death
monoamine oxidase Dopamine levels are reduced by _______ _______, which generates H2O2
chain reactions The RNOS and hydroxyl radical lead to radical _____ ______ that result in lipid peroxidation, protein oxidation, the formation of lipofuscin, and neuronal degeneration
lipofuscin The pigment ____consist of a heterogeneous mixture of crosslinked polymerized lipids and protein formed by reactions between amino acid residues and lipid peroxidation products, such as malondialdehyde.
“liver spots”, When these dark pigments appear on the skin of the hands in aged individuals, they are referred to as _____ _____a traditional hallmark of aging
NADPH ______is a key ingredient for the activity of macrophages and enzymes involved in defending against oxidative stress
Congenital methemoglobinemia metHb reductase deficiency – cyanotic Treatment with high doses of vitamin C
metHb Normally <1 % of Hb is _____?
Copper, Zinc Superoxide dismutase1 – a ___ and ____ containing cytosolic enzyme that catalyzes: O2-. + 2H+ + e- - H2O2
Vitamin E Vitamin C (fruits), ______(vegetable oils, nuts etc), Vitamin A (dairy products), and β-carotene (vegetables) all serve as antioxidants.
antioxidants Good _______ have relatively unreactive radical form, are easily repaired/replaced and decay to harmless products
aldehydes Reactive _____ are generated as; Products from sugar metabolism, Glycoxidation, Lipid peroxidation, Myeloperoxidase (HOCl)
2,4 dNP Carbonyl-proteins measured with ____ Increase is associated with disease and aging
CD36 scavenger Particles become oxidized by exposure to radicals and ROS (including NO2.). No longer good ligands for LDL receptors. Oxidation makes them good ligands for ____ _____ receptor
apoptosis Mitochondrial structure preserved nuclear fragments. [shrinking/blebbing->fragmentation]
necrosis Mitochondrial changes chromatin pattern is preserved.[ swelling->rupture]
Necrosis pathological cell death,Release of enzymes, Release of pro-inflammatory products, Ingress of neutrophils followed by macrophages, Active inflammation and scarring
Apoptosis programmed cell death Retention of cellular enzymes in apopotic bodies No release of pro-inflammatory products Ingestion by adjacent cells or tissue macrophages Atrophy, but no scarring
procaspase 9 Mitochondrial Cytochrome c released,Binds to Apaf-1, Associates with ______.Activates caspase 3 proteolytically, Caspase cascade culminates in apoptosis
Glycoxidation ________: glucose, the fundamental source of energy, reacts with and crosslinks essential molecules, including proteins and DNA
Amadori product Glucose reacts with a lysine to form an _____ ____or glycated protein. A good example is the reaction between HbA and glucose to form HbA1c
Pentosidine Glycated product with arginine and oxidation can link to another lysine cross-linking two proteins = ________ formation – an advanced glycosylation end-product (AGE)
Macrophages ______Have scavenger receptors for AGE’s. AGE’s are broken down and the breakdown products are exocytozed and eventually cleared via the kidneys
Cross-link breakers Drugs that break sugar-protein bonds in AGE’s
metformin The commonest drug used to treat diabetes Animal studies and investigations with ______-treated diabetics clearly show that ________ can prolong life expectancy
glucose Non-enzymic addition of ______to DNA gradually damages DNA and could lead to loss of gene function
Heat shock proteins Proteins produced by cells in response to stress (toxins, heavy metals, psychological stress).Function is to help cell dismantle and dispose of damaged proteins and to promote synthesis and transport of new proteins
HSP-70 _____levels lower in old versus young animals. _____ decreases in cultured human cells as they approach senescence.
Heat shock protein[HSP] In adrenal cortex, ______ ______ ______ expression is closely linked to release of stress hormones (epinephrine, glucocorticoids etc)
10,000 It is estimated that each cell in the body has to deal with __#__free radicals each day!
anti-oxidant defenses Superoxide dismutase - SOD-1 (Cu/Zn - cytosol), SOD-2 (Mn - mitochondria) and SOD-3 (Cu/Zn - extracellular),Catalase, Glutathione system, Melatonin (N-acetyl-5-methoxytryptamine),Uric acid, Ascorbate, α-tocopherol are all part of
Oxidative stress ___ _____ arises when there is an inbalance between radical formation and the antioxidant defences.
Synthetic antioxidants These are compounds like BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole), also propyl gallate and tert- butyl hydroquinone
plant Vitamin C (ascorbate), vitamin E (α-tocopherol and tocotrienols) and β-carotene are examples of ____ antioxidants.
plant antioxidants Curcumin, cyanidin, cholorgenic acid, reservatrol, lycopene, rutin are all _____ ______
Rutin (quercetin-3-O-rutinoside or sophorin) An antioxidant - attaches to Fe2+, preventing free radical formation from H2O2 - anti-platelet activity - Inhibitor of angiogenesis (? Cancer treatment)
Cyanidin An anthocyanidin found in red grapes and many berry fruits. Putative antioxidant/radical scavenger that protects against CVD and cancer. Also claimed to inhibit development of obesity and type II diabetes
Chlorogenic acid An antioxidant found in potato, peach, prune and coffee - may cause laxative effect of prunes. Modestly decrease BP; Reduce colon cancer in mice and Induce DNA repair enzymes PARP and PMS2
Resveratrol A stilbenoid - one of the most promising plant antoxidants - found in red grapes, juice and red wine.Putatively beneficial in CVD - high doses decrease BP
Lycopene Responsible for the red colour of tomatoes, water melon and pink guava. Absorbed from lipid micelles in the small intestine and transported in chylomicrons, it ends up in LDL and VLDL and fatty tissues like adipose, adrenal , prostate etc
folate the addition of ____ to flour and breads consumed by pregnant women to avoid neural tube defects in the developing child.
B12 atrophic gastritis which can lead to ___ deficiency
25 g, 35 g The DRI for fiber is the RDA set at 14 g/1000kcal, which is about ____ and ____ for women and men respectively. Most Americans consume less than half this amount
Eicosapentaenoic[EPA], docosahexaenoic[DHA] Fish oils:The n-3 fatty acids; _____ and _____ acids have beneficial effects for the heart – lowering BP, preventing arrhythmias, lowering TAGs etc
Allicin ____is the active principle of garlic. there is some evidence that it can slow development of atherosclerosis, balance lipoproteins, modestly reduce BP and show anti-thrombotic and anti-inflammatory activities.
α-galactosidase Beano contains_______ an enzyme that prevents gas formation after consuming beans etc.
ergogenic Dietary supplementation of protein above what is needed to maintain nitrogen balance does not furnish any extra ______ benefit
Valine, leucine, isoleucine ranched chain amino acids - it has been suggested that____, ____, and____ together with glutamine may affect central fatigue and exercise-induced immune suppression,but their ergogenic value during prolonged exercise is equivocal
Kwashiorkor protein deprivation is greater than the reduction in total calories,severe loss of visceral protein,children >1yo,stunted growth, edema, skin lesions, depigmented hair, anorexia, enlarged fatty liver, decreased plasma albumin concentration
Marasmus calorie deprivation is greater than the reduction in protein, children <1yo, arrested growth, extreme muscle wasting (shrunken with skin & bones only - old monk face), weakness and anemia. Intake of all nutrients decreased including carbohydrates
Cachexia (Gr. Kakos hexia) wasting syndrome – loss of body mass that cannot be reversed nutritionally even if calorie intake is increased –End-stage cancer TB and HIV/Aids (“slim disease”),Congestive heart failure,COPD,Severe schizophrenia (= vesanic cachexia)
Bacteria, mites _____, fungi and _____transform plain coagulated milk into noble cheeses
Microorganisms _______ transform salted minced meats into salamis and chorizos etc.
instant coffee Freeze drying is an industrial technique that use high vacuum to remove water from a product that has been frozen. its main use is in_____ _______ production.
Fermentation is a process of preservation that use micro-organisms to change a foodstuff into a different product that harmful bacteria can’t spoil – cabbage can be preserved as sauerkraut, also certain types of fish
trans-unsaturated Introducing ______-______ bonds into TAG acyl chains and increasing the risk of CHD
mercury The Institute for Agriculture and Trade Policy recently found high levels of ______ in about a third of leading products that listed HFCS or fructose as the first or second main ingredient!
Jeanne Louise Calment _________ passed away in 1998 aged 123 years
cancer, sarcopenia Leading causes of death-Present: heart disease, ________, neurodegenerative disease, _________
Programmed longevity theory that Aging is the result of switching on and off of certain genes that then cause senescence
Somatic DNA damage theory that Genetic mutations occur and accumulate with age, causing cells to malfunction. Damage to mitochondrial DNA leads to mitochondrial dysfunction
Antagonistic pleiotropy theory that genes that are beneficial at younger ages are harmful at older ages
hydroxyl radical thought to be the most dangerous ROS
respiratory burst The ______ _______ is a major source of superoxide, hydrogen peroxide, the hydroxyl radical, hypochlorous acid (HOCl), and RNOS
Created by: SabaMDJuan