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Unformatted text preview: Clicker Question Which of the following is not part of the “fight or flight” not part response to stress? A. B. C. D. E. Dilation of the bronchi Release of sugar from the liver Dilation of arteries that bring blood to the heart and brain Constriction of the arteries that bring blood to the stomach Increased secretion of amylase from the salivary glands Where are we?
• Last time I discussed…
– homeostasis, the mechanisms the body uses to maintain stability of the internal milieu that surrounds the cells of the body. – allostasis, the mechanisms the body uses to switch from the “rest and allostasis, digest” mode to the unsustainable “fight or flight” mode. – I also discussed stress (hypostress, hyperstress, eustress, and distress) hypostress, hyperstress, eustress, and why too much stress is harmful. Aging • This time I will discuss…
– – – – – how too much sugar and oxygen can speed up senescence (aging). too (aging). the virtue of moderation death organ donation burial There are many factors that influence aging, including genetic environmental genetic, environmental and nutritional factors.…and we nutritional factors.…and all age…. Jennifer Jennifer Gray Erik Estrada 1 Melanie Griffith Michael Douglas Cher Cher Sharon Stone Mickey Rouke Farrah Fawcett 2 Wayne Newton Cybill Shepherd Kathleen Turner Cheryl Tiegs Keith Richards 3 Sugar, Oxygen and Aging
• I am going to discuss two factors that promote the sugar aging process: sugar and oxygen oxygen. • These are two things we These are two things we surely can’t surely can’t live without; and in many cases, two things that may accelerate may dying. • Moderation: too much of a good thing is not necessarily a good thing. Popular Science Monthly 4 5 6 We Would Never Fall for These Ads Today, But… We Won’t Get Fooled Again! www.openhappiness.tv Calories in Food Come from Carbohydrates, Proteins and Fat. Although Low-Fat Can Mean More Protein and/or More Carbohydrate, it Often Means High Sugar. Thinking in Terms of False Dichotomies Gives Rise to Good Guys or Bad Guys What if It's All Been a Big Fat Lie? “Sugar is Good!” “Sugar is Bad!” “Fat is Good!” “Fat is Bad!” “Protein is Good!” “Protein is Bad!”
New York Times, July 7, 2002 7 False Dichotomies? The Middle Way
"To go beyond is as wrong as to fall short.”
--From the Analects by Confucius The Analects The Doctrine of the Mean Confucius Family and DNA Testing Meden Agan: Nothing in Excess Agan: Little Known Chemistry of Sugar and Oxygen The Maillard Reaction
• Louis Camille Maillard (1912) was a French physician and chemist who, after studying the chemical reactions that led to the color of urine, was trying to figure out how amino acids bonded together to form proteins. In doing so, he heated amino acid am ids with sugars (which he used as a sugars dehydrating agent) and noticed that a nonnon-enzymatic browning reaction occurred serendipitously occurred serendipitously. • He suggested that the reaction might take place in the human body, and he even imagined the critical role we now know it plays in diabetes. diabetes 8 Food Science and the Maillard Reaction
that developed in the powdered eggs eaten by GIs during WWII. Food scientists originally studied the Maillard Maillard reaction to understand the cause of the horrible flavors Food Science and the Maillard Reaction
• Then Food scientists studied the Maillard reaction; Food Maillard to learn how it improves the color, aroma and flavor of cooked foods.
– Colors of toast, beer, coffee, chocolate and maple syrup are due due to the Maillard reaction. – Aromas of bread, popcorn, tortillas and aromatic rice are due of to the Maillard reaction. – Flavors of browned or roasted beef are due to the Maillard reaction. Maillard Reaction: Color • Still, the biologists ignored Maillard’s work until 1968. ignored Maillard’s Maillard Maillard Reaction: Aromas Maillard Reaction: Flavor 9 The Maillard Reaction Occurs In Mixtures of Proteins and Sugars The Maillard Reaction Gives the Brown Color to Humus in the Soil Albumen (mixture of white proteins) that makes up the that egg white was used to make photographic prints. The browning of the albumin is due to the Maillard reaction.
http://users.telenet.be/thomasweynants/stereohttp://users.telenet.be/thomasweynants/stereo-nudes.html http://albumen.stanford.edu/library/c20/messier1991a.html Samuel Rahbar
Samuel Rahbar (1960s) serendipitously serendipitously found, while searching for mutations in the mutations in the hemoglobin hemoglobin molecule in the ethnically diverse population of Iran, that diabetics had glucose diabetics had glucose attached attached to their hemoglobin hemoglobin. Enzymatic vs. Non-Enzymatic Reactions
Up until now, I have emphasized how important enzymes are in catalyzing a diverse array of chemical reactions in the body. Enzymatic reactions have Enzymatic reactions have the advantage of being controlled and controllable. But just because most reactions are catalyzed by enzymes, it does not mean that nonenzymatic reactions can’t also occur in the body. Enzymatic Enzymatic vs. Non-Enzymatic Reactions: Another NonCase of Monocausal Thinking Static Static Cling (an inability to accept change) glycation Until Rahbar discovered glycation (non of enzymatic addition of glucose) of hemoglobin in diabetics, biologists had ignored the Maillard nonreaction, thinking that the non-enzymatic addition of glucose to the amino-containing gl noproteins groups of proteins required the high temperature attained while cooking, not the low temperatures found in the human body. Besides, it was already known that biological systems used enzymes to put sugars on proteins, a process known as glycosylation…and one cause glycosylation…and was enough. 10 The Maillard Reaction Can Affect Many Proteins • Rahbar's discovery of Advanced Advanced Glycation End Products (AGE) glycated glycated hemoglobin
changed our way of thinking. • Soon it was discovered that many proteins can participate in the Maillard Reaction. • The Maillard Reaction can occur with any protein if there is Maillard too much sugar around. long protein • A long lived protein, like the protein that makes up the lens of the eyes, can bind many sugars. The glycated protein is further attacked by other glucose molecules. Such proteins are called, “advanced glycation end products” (AGEs). AGEs). Advanced Glycation End Products (AGE)
• AGEs can crosslink to other AGEs and form networks of glycated proteins that are irreversibly damages irreversibly damages. • The formation and crosslinking of AGEs is free enhanced by free radicals. Correlation of AGEs with Aging and Disease
• AGEs accumulate with age. age elevated • Because of their elevated blood sugar, diabetics accumulate AGEs earlier in life. • Depending where AGEs occur, they they can cause impaired function of that organ. www.immortalhumans.com • The buildup of AGEs is correlated with kidney disease, eye damage, heart disease, atherosclerosis, nerve damage and Alzheimer's disease. The A1c Now Monitor Measures Glycated Hemoglobin AntiAnti-Aging Cream Treats and Controls AGEs
“The same glucose (sugar) that provides energy for our cells can also react with proteins, including the skin’s collagen. This reaction results in the formation of Advanced Glycation End-products (AGEs), Gl (AGE which can contribute to loss of elasticity, wrinkles, inﬂammation, inhibited skin cell growth and accelerated aging . Because we understand these triggers, skin care skin • Pyridorin (pyridoxamine), a member of the vitamin B6 family, blocks AGE formation. This and other inhibitors of the Maillard reaction may soon be available as medications. nephrogenex professionals are better equipped to effectively treat, and control, the signs of skin aging.”
www.dermalogica.com Kiss and Make Up 11 Joseph Priestley
Joseph Priestley discovered that we need oxygen to live and and plants produce that oxygen. He also suggested that too much oxygen may be detrimental. Joseph Priestley Tried the Pure Air He Produced on Himself
“The feeling of it to my lungs was not sensibly different from that of common air; but I fancied that my breast felt particularly light and easy for some time afterwards. Who can tell but that, in time, this pure air may become a fashionable article in luxury….From the greater strength and vivacity of the flame of a candle, in this pure air, it may be conjectured, that it might be particularly salutary to the lungs in certain morbid cases, when the common air would not be sufficient to carry off the putrid effluvium fast enough.” Oxygen Bars: You Can Sell Anything Oxygen Bars: Rent Them for Parties Joseph Priestley: A moralist
“But, perhaps, we may also infer from these experiments, that though pure dephlogisticated air [oxygen] might be very useful as a medicine, it might not be so proper for us in the usual healthy state of the body; for, as a candle candle burns out much faster in dephlogisticated than in common air, so we might, as may be said, live out too fast and the animal powers be too soon exhausted in this pure kind of air. A moralist, at least, may say, that the air which nature has provided for us is as good as we deserve.” Free Radicals
• Oxygen is typically reduced to oxygen dihydride (water, H2O, OH2) OH at the end of the respiratory chain in the mitochondria. Some of the oxygen (O2) is partially reduced to form superoxide by the electron su transport chain. Superoxide (O2.- ) is free a free radical. • A free radical is a chemical with an free unpaired electron. Free radicals are very very reactive because electrons like to pair up to form stable twotwoelectron bonds in uncontrolled nonnonenzymatic reactions. 12 The Production of Superoxide Starts a Chain Reaction
O2 + 4H+ + 4e- → → 2H20 (>95% of the time) → 2O2.- (<5% of the time) When the oxygen becomes a free radical, it free steals an electron from another molecule in the cell. The electron donating molecule is then electron left with an unpaired electron, causing it to become become a free radical too. Thus a selfselfperpetuating chain reaction occurs where the structure and function of many molecules can be altered very rapidly. Superoxide Can Enter Our Lungs from Cigarette Smoke
Superoxide Superoxide and other free radicals also di occur in cigarette smoke. Oxidative Damage
The free radicals formed by the electron transport chain and cigarette smoke can cause oxidative damage to: id
– Lipids in the cell membrane which causes leakage into and out of cells. – Proteins, leading to loss of enzyme activity. – DNA, leading to mutations. Theory of Aging
Aging Aging and its associated diseases may result, in part, from the from the Albert Szent-Gyorgyi thought that antioxidants, Szentwhich quench free radicals, were important for good health, but was ignored accumulated accumulated changes that happen
to molecules and cells that are initiated by glucose and free glucose and free radicals. 13 Addison’s Disease and Browning
• Szent-Gyorgyi was interested in the function of the cortex of the adrenal gland. Addison’s disease is a malfunction in the adrenal gland and a patient’s skin becomes brown before the person dies of the disease. • Szent-Gyorgyi realized that a similar browning reaction occurs with certain fruits and vegetables, like apples, bananas and potatoes.
JFK had Addison’s disease. Addison’s Disease and Browning
• Szent-Gyorgyi was convinced that there are in principle no (except for the cost of doing experiments) when it comes to basic biological mechanisms. So he set out to study the browning reaction in the potato. • He did this in the hope of discovering the key to the understanding of adrenal function. fundamental differences between animals and plants, or cabbages and kings A Dead End
• Szent-Gyorgyi showed that potatoes contain an enzyme called, polyphenol oxidase. • Since the enzyme is in the plastids and the polyphenol is in the vacuole in an polyphenol is in the vacuole, in an undamaged potato, the enzyme and the substrate do not combine and the potato stays white. • When the cells are damaged, the enzyme oxidizes polyphenol to quinone. The quinones then polymerize and form brown pigments. A Dead End
• However, this system was a dead end and gave him no information about adrenal function and Addison’s disease. • So Szent-Gyorgyi turned to plants like turnip and cabbage, which do not turn brown when they are bruised. Peroxide and Benzidine → Blue
• These plants contain a peroxidase. This enzyme can oxidize various reduced molecules as it molecules as it reduces peroxide (H2O2) to make water (2H2O). • If benzidine is added to purified peroxidase, a deep-blue color appears immediately. Discovery of a New Antioxidant or Reducing Substance
• When Szent-Gyorgyi added benzidine to some juice that had been squeezed from the plant, the blue pigment appeared, but only after a small delay of about a second. • Szent-Gyorgyi isolated large quantities of the substance that inhibited the oxidation of benzidine th th from Hungarian peppers. He showed that it had the formula C6H8O6 and was thus related to the carbohydrates. • Szent-Gyorgyi isolated the same substance from adrenal glands. • “There was great excitement in my little basement room in Groningen, when I found that the adrenal cortex contained a similar reducing substance in relatively large quantities.” 14 A Rose by any other Name…
5H+ + 5eAscorbic Acid Does Not Become A Free Radical After Donating (or Losing) Electrons 8H+ + 8e- 7H+ + 7e- • Szent-Gyorgyi called this chemical ignose because after isolating it he was ignorant of most of its properties. • Arthur Harden, the journal editor, refused to accept SzentGyorgyi’s paper on ignose, so Szent-Gyorgyi changed its name to Godnose. • Szent-Gyorgyi finally accepted the editor’s proposed moniker “hexuronic acid” since it was a six carbon sugar acid. • Eventually, Szent-Gyorgyi discovered that hexuronic acid prevented scurvy and was thus vitamin C. He renamed it ascorbic acid for its antiscorbutic activity and won the Nobel Prize in and won the Nobel Prize in 1937. • Szent Gyorgyi suggested that vitamin C and other antioxidants antioxidants could be very important to human health since they neutralize free free radicals. Addison’s Disease and Cortisol
• Szent-Gyorgyi found that ascorbic acid could not replace the faulty adrenal glands, but it could prevent the increased pigmentation in patients with Addison’s disease. • We now know that added cortisol can be used to treat Addison’s disease, which results from the lack of production of cortisol by the adrenal cortex. • This shows us that the production of the stress hormone, cortisol, is not “bad” but required for a healthy life. SzentSzent-Gyorgyi Discovered Vitamin C, because he was aware of a 1 sec time lag.
“Discovery consists of looking at the same thing as thin everyone else and thinking something different.” Albert Szent-Gyorgyi Szent(1962) Antioxidant Protection After the Nazis took over, Szent-Gyorgyi helped his Jewish friends, including Hans Krebs to escape and was wanted by the Gestapo. He emigrated to Woods Hole, MA in 1947, after the Communists took control of Hungary. • Antioxidants, including vitamins C and E neutralize free vitamins radicals by donating one of their own electrons, ending the "electron"electron-stealing" reaction. • Antioxidants do not become free radicals in the process because they remain stable after donating an electron. 15 Antioxidants and Commercial Products Cure for Aging?
The The U.S. Food and Drug Administration consuming recommends consuming many fruits and vegetables. They believe that a diet rich in fruits and vegetables is more effective than supplements because each fruit fruit and vegetable has hundreds of phytochemicals phytochemicals. The protection from disease is likely a result of a combination rather than any single factor. The extensive research on the effects of these antioxidants on both aging and disease, indicates, that, like diseases, some aspects of aging can be prevented. neimanmarcus.com Nuskin Science of Aging Superoxide Superoxide Dismutase
• An important part of the antioxidant defense system inside cells are the antioxidant antioxidant enzymes. • For example, superoxide dismutase (SOD) For example superoxide dismutase (SOD) converts converts superoxide into the less reactive chemicals (peroxide and oxygen). SOD → H2O2 + O2 They Were Laughed At
In 1968, Joe McCord and Irwin Fridovich serendipitously superoxide discovered superoxide dismutase (SOD) as a contaminant of other enzymes They suggested that it enzymes. They suggested that it functioned functioned in the body as a defense defense against endogenously generated superoxide. Although
they were laughed at, at the time, today, their discovery is recognized as the basis of a whole field of biology and medicine. 2O2.- + 2H+ Lou Lou Gehrig’s Disease
• Amyotrophic lateral sclerosis (ALS), better Lou known as Lou Gehrig's disease. results from the degeneration degeneration of motor neurons. • The gene for gene for is defective in 20% of people with inherited amyotrophic lateral sclerosis (ALS). Superoxide Superoxide Dismutase in Commercial Products superoxide superoxide dismutase 16 Some Contributors to Aging
• Nutritional Influences: – Too many sugars speed up the aging process by forming sugars speed AGEs AGEs by the non-enzymatic Maillard reaction. nonMaillard – Free radicals, formed in the presence of oxygen speed up oxygen speed the aging process by causing damage to lipids (membranes), li proteins (enzymes) and DNA (mutations) and promote crosscross-linking of AGEs, which results in heart disease, kidney disease, eye damage, nerve damage, atherosclerosis and Alzheimer’s. antioxidants vitamins – Lots of antioxidants, including vitamins C and E slow scavenging down the aging process by scavenging free radicals. Some Contributors to Aging
• Environmental Influences: – Smoking speeds up the aging process by forming free free radicals. • Genetic Influences: – A defective superoxide superoxide dismutase enzyme speeds up the aging process by not being able to remove the free super oxide free radical.
www.glisodininfo.com www.cell-logic.com Aging Eventually Leads to Death Woody Allen
“I am not afraid of death, I just don’t want to be there when it happens.” If you would behold the spirit of death, open your heart wide unto the body of life. For life and death are one, even as the river and sea are one. -- from The Prophet by Kahlil Gibran 17 Stopping by Woods on a Snowy Evening Robert Frost Do not Go Gentle into that Good Night Dylan Thomas Stopping by Woods on a Snowy Evening Do nor go gentle into that good night Death Before Aging
• On September 29, 1998, after being viciously bullied, 13 year-old Jared yearHigh called his father at High called his father at work work to say goodgoodbye. While on the phone with him, Jared shot himself, dying instantly. • He never got to age.
www.bullycide.org Death before Aging
• On January 14, 2010, after being viciously bullied, 15 year-old bullied, 15 year old Phoebe Phoebe Prince went home and hung herself. • She never got to age. Death Allows the Adequate Food Supply Necessary for Civilization
When When the Navajo came into the world, they asked, “Will we die or will we live forever?” Coyote decided the question by throwing a stone into the water. He said, “If it floats, we will live forever; if it sinks, sinks, we will die.” It sank, and the Navajo became angry. Coyote explained to them that “If we all live and continue to increase as we have done in the past, the earth will be too small to hold us, and there will be no room for the cornfields. It is better that each of us should live but a limited time on this earth, then leave and make room for the children.” Cherry Blossoms or Dandelions
• Does the degree that we take ourselves and each other for granted depend on out out life span? • If we lived for hundreds of years would we treat each other more like dandelions than cherry blossoms? 18 Organ and Tissue Donation: A Miraculous Gift that the Dead can Give to the Living
• Skin, cornea, bone, cartilage, blood, veins, bone marrow, kidney, liver, heart, pancreas, liver intestine or lung can be donated from cadavers. cadavers • Bone marrow, a kidney, portions of a liver or a lung, and umbilical cord stem cells can be donated from one living person to another.
organdonor.gov liverfoundation.org transplants.org marrow.org “DEATH‘S stamp gives value to the coin of life, making it possible to buy with life what is truly precious.”
--- From Stray Birds by Rabindranath Tagore Statistics on Organ Transplants Organ Trafficking www.humantrafficking.org There are More Potential Organ Receivers than Donors
• Would you accept an organ to save your life? • Would you donate organs when you die? when you die? • Should a potential donor have priority in getting an organ over a declared nonnondonor? • Should a gift have any strings attached to it? • What is fair? Burial in a Sarcophagus
• Long ago, people believed that the human body was decomposed decomposed by the limestone that made up the sarcophagus sarcophagus itself itself. • This is how the sarcophagus got its name. Sarco is Greek for flesh and phagus is Greek flesh for eating. eating • Now we know that microorganisms microorganisms and small animals cause the body to decompose. 19 Embalming Prevented the Decomposition of Union Soldiers Killed on the Battlefield so that they could be Shipped Home for Burial. From Parlour to Living Room
• When death from disease was a commonplace and unpredictable, the recentlyrecentlydeceased were laid out in the parlour while the funeral arrangements were being made. • With the decrease in the death rate from disease, the parlour parlour was replaced with the “living room” and parlours reappeared as funeral parlours. parlours. nationalgeographic.com National Museum of Funeral History Green Cemeteries A. Carl Leopold
Carl Leopold, son of Aldo Leopold, who wrote A Sand County Almanac, Sand was a founder of Greensprings. Greensprings. Carl completed the circle begun by the his father’s quest to understand how to live on the land without spoiling it. Carl’s molecules and minerals will be recycled into the fruits of the native bushes that will feed the native birds and provide energy for their songs. • There are seven natural cemetery preserves in the United States. • Greensprings Natural Cemetery Preserve on Irish Hill Road in Newfield is New York State's first natural cemetery.
– – Embalming fluid is not used Caskets are biodegradable, made from local wood or optional.
www.naturalburial.org Good Good Luck on Prelim I
• There will be an optional review session in Call Auditorium on Wednesday, February 24 at 9:05. • There will not be a clicker question question. • I will sum up the first part of the semester during that session and answer any questions you may have. • Remember what Louis Pasteur said, “chance favors a prepared “chance mind.” 20 ...
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This document was uploaded on 11/09/2010.
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