Aging and Antioxidants: finding a magic bullet in a biological battlefield of free radicals

Rich in phytonutrients and antioxidants,
these fruits help protect your body against free radicals.
Photo credit: Click here

Why do we age? Scientists have been searching to elucidate the mechanisms involved in the aging process for many years and have come up with several explanations. Because of the information we have, we are now able to slow the maturity rate of our bodies. Life spans are longer today than they were generations ago and many age-related diseases, although still among us, are more preventable and manageable.  We do not know how to completely stop aging, but we do know that it is a progressive process involving oxidation, free radicals, and various complex activities that occur at the cellular level. And we also know that intervention with antioxidants is highly effective in slowing this process.
 

Reactive Oxygen Species (ROS).
Photo credit: Joyce E.M. Wall
(original artwork; Copyright ©2009 Joyce E.M. Wall)

Oxidation and Free Radicals [1]
In the body, oxidation is a natural process that turns oxygen into energy. It also produces free radicals, which are toxins that damage cells and DNA. More specifically, free radicals are atoms that have one or more unpaired electrons and can have a positive, negative or neutral charge. There are various types of radicals, which include nitric acid, ozone, and transition metals such as iron and copper; but those of most concern in biological systems are derived from oxygen, which are known as reactive oxygen species (ROS). Oxygen has two unpaired electrons in separate orbitals in its outer shell. It is this electronic structure that makes oxygen especially susceptible to radical formation. Sequential reduction of molecular oxygen leads to the formation of ROS:
   •    superoxide anion
   •    peroxide (hydrogen peroxide)
   •    hydroxyl radical

Oxygen-derived radicals are formed in mitochondria as oxygen and reduced along the electron transport chain. They are generated on a continual basis and are part of normal aerobic life. ROS are formed as intermediates in a variety of enzyme reactions but may be overproduced in cells in certain situations:
   •    White blood cells such as neutrophils produce oxygen radicals, which are used in the host defense to kill invading pathogens.
   •    Cells exposed to abnormal environments means that cells that have undergone hypoxia or hyperoxia generate abundant ROS, which can be damaging. Several drugs have oxidizing effects on cells and lead to production of oxygen radicals.
   •    Ionizing radiation generates oxygen radicals within biological systems and produces more damaging effects in well oxygenated tissues rather than in oxygen deficient tissues.

Free radicals play a crucial role in the immune system by protecting the body from potentially harmful pathogens or foreign particles that enter it. The free radicals are formed as necessary intermediates in a variety of normal biochemical reactions, but when generated in excess or not controlled, they can wreak havoc on a broad range of molecules. They have extremely high chemical reactivity, which explains their normal biological activities as well as how they inflict damage on cells. Phagocytic cells generate free radicals to kill invading pathogens and they are also involved in intercellular and intracellular signaling. For example, addition of the ROS superoxide or hydrogen peroxide to various types of cultured cells results in an increased rate of DNA replication and cell proliferation (the radicals function as mitogens in that they encourage cell division or mitosis). But ROS can also be toxic to cells since they possess an unpaired electron making them highly reactive and able to damage cellular membranes and macromolecules, which include lipids, proteins and nucleic acids. Oxidative damage from free radicals is linked to several diseases associated with age, which includes cancer and neurodegenerative diseases (i.e. Alzheimer’s and Parkinson’s diseases).

Antioxidants neutralize free radicals.
Photo credit: Joyce E.M. Wall
(original artwork; Copyright ©2009 Joyce E.M. Wall)

Antioxidants [2]
Antioxidants destroy free radicals before they have the opportunity to harm us and as we age, this process becomes less efficient. Dietary intake of antioxidants through foods and vitamin supplementation can limit the harmful effects of oxidative damage and slow the aging process.  An antioxidant neutralizes a free radical by donating an electron to it; thus blocking the oxidative process. The antioxidant itself does not become a free radical even though it gives up an electron (it is stable in either form) but it does become oxidized and so there is a constant need for replenishment. Antioxidants work by either of these methods:
   •    Chain-breaking: A free radical releases or steals an electron, a second radical is formed, which in turn does the same thing to a third molecule and so on. This generation of unstable products is a continuing process that will go on until termination occurs whereby either the radical is stabilized by a chain-breaking antioxidant (beta-carotene, vitamins C, E) or simply decays into a harmless product.
   •    Preventive: Antioxidants prevent oxidation by reducing the rate of chain initiation. They scavenge initiating radicals, and so can thwart an oxidation chain from ever starting. They also prevent oxidation by stabilizing transition metal radicals (copper and iron).
Antioxidants include: [3]
Vitamins:
   •    A (retinol), synthesized from beta-carotene
   •    C (ascorbic acid)
   •    E (tocepherol)
Cofactors and Minerals:
   •    Coenzyme Q10
   •    Manganese (when part of superoxidase dismutase (SOD))
   •    Iodide
Hormones:
   •    Melatonin (plays a role in the regulation of circadian rhythms or sleep/wake cycle)
Carotenoid terpenoids:
Example: carrots, broccoli, green leafy vegetables, and tomatoes
   •    Alpha and beta-carotene
   •    Astaxanthin, Canthaxanthin, and Zeaxanthin (plant pigments)
   •    Lutein
   •    Lycopene
Flavonoids Polyphenolics:
Example: berries, walnuts, soy, peanuts, bananas, red grapes, coffee and tea
   •    Flavones: Apigenin, Luteolin, Tangeritin
   •    Flavonols: Isorhamnetin, Kaempferol, Myricetin, Proanthocyanidins, Tannins, Quercetin
   •    Flavanones: Eriodictyol, Hesperetin, Naringenin
   •    Flavanols and polymers: Catechin, Gallocatechin, Epicatechin, Theaflavin, Thearubigins
   •    Isoflavone phytoestrogens: Daidzein, Genistein, Glycitein
   •    Stilbenoids: Resveratrol, Pterostilbene
   •    Anthocyanins: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin
Phenolic acids and Ester derivatives:
Example: Echinacea, cinnamon, blueberries, tomatoes, brown rice, whole wheat, oats, peanuts, pineapples, strawberries, witch hazel, sage, oregano, willow bark
   •    Chicoric acid, Chlorogenic acid, Cinnamic acid (ferulic acid), Ellagic acid, Gallic acid, Rosmarinic acid, Salicylic acid
Nonflavonoid Phenolics:
Example: milk thistle
   •    Curcumin, Flavonolignans, Xanthones, Eugenol
Other:
Example: broccoli, pumpkin seeds, beans, metabolic products in the body
   •    Bilirubin, Citric acid, Oxalic acid, Phytic acid, Lignan, N-Acetylcysteine, R-α-Lipoic acid, Uric acid

Aging—why we do it [4][5]
Senescence (Latin=senex, means “old man”) refers to the biological changes and all the processes the body undergoes as it ages. Antioxidants are rescuing our cells from oxidative damage, but still we continue to age. Explanations about why we age include:

Problems with proteins:
Dr. Oz explains that the reason we age is because our body has problems producing the proteins that are essential for our health, which is due to free radicals. The free radicals attach to other molecules to stabilize themselves and create more free radicals. This chain reaction occurs until the cells are dead. It is this oxidation process from the free radical chain that is aging and slowly killing us. We can halt this process, however, with antioxidants.  A good example of the effects of oxidative stress from free radicals is the apple. Slice an apple in half and leave it exposed to the air and it will turn brown. This is oxidation and is what occurs in the body.  Coat the other half of the apple with an antioxidant and it is more likely that the apple will be preserved in a healthy state. So, the oxidation process causes the body to deteriorate and die. Free radicals disturb the process of protein synthesis and so contribute to the aging process.

Telomeres
In the 1970s, Elizabeth Blackburn (Yale University) identified telomeres, which are cap-like structures that protect DNA as it is copied in the process of cell division. Telomeres are DNA sequences at the tips of human chromosomes that shorten as we age and are thought to have a significant impact on cells. Research is focused on the enzyme telomerase (replenishes telomeres in the cell) and finding out if short telomeres cause aging or age-related diseases.

DNA Damage and Repair
DNA is damaged by internal and external toxins at any given moment. The body has developed intricate repair systems that maintain the integrity of our genetic code, our cells and their functional properties. Over time, DNA repair systems falter and the accumulation of uncorrected DNA damage over years may have a significant impact on aging.

Mitochondrial Aging
Mitochondria are responsible for energy conversion in the cell. But they also produce free radicals, which can damage the cells and DNA. The mitochondria themselves are vulnerable to the injurious effects of the free radicals they produce. That injury is a critical part of the aging process, and perhaps a cause of various age-related diseases.

Cellular Senescence
Cellular senescence is the phenomenon by which normal diploid cells in the body lose the ability to divide, typically after about 50 cell divisions in vitro (it is a cellular trait known as replicative senescence and is thought to prevent against cancer). So, most human cells can only reproduce a limited number of times before they lose their ability to divide. The benefits of cellular senescence decline as life span increases, which results in a biological compromise of the senescent cells in comparison with non-senescent cells.

Scientists are working to understand senescence and the various mechanisms involved that elicit changes during the life cycle. These changes affect cells, tissues, and organs during the aging process. Most, if not all, of them have some association and correlation with oxidative stress from free radical formation. Events such as this modify the cell and impair its ability to replicate, synthesize new proteins, and maintain its overall structural and functional integrity. Gene expression, enzymatic activity, signaling pathways and an unhealthy accumulation of aggregates inside and outside of the cell are also consequential effects. Repairs to the cell are a result of these events, but if the repairs are outpaced by the cumulative effects of the harmful modifications, then the cell deteriorates over time. The repair mechanisms slow down, damaged cells release chemicals that destroy other healthy cells, the immune system becomes less efficient, stem cells stop dividing and regenerating tissues, and health is compromised. So, in order to slow or even halt the aging process to prolong and maintain a healthy life in a biological battlefield of free radicals, antioxidants may indeed be the anti-aging magic bullet to accomplish just that.

Click here to enlarge
Senescence (biological changes and all the processes the body undergoes as it ages) results in observable changes to the body, which affects both its structural and functional capabilities. [6]
The body undergoes a complexity of biological processes and free radicals, in excess, have an influential role in these changes.
Photo credit: TISSUE, ORGAN, & WHOLE BODY: PHYSIOLOGY & PATHOLOGY
Arrangement, text, & art by John D. Furber
Rev. 9 June 2009  © 2000 - 2009 John D. Furber, All rights reserved.   
johnfurber@LegendaryPharma.com  
PO Box 14200  Gainesville FL 32604-2200  USA
http://legendarypharma.com/chartbg.html
" Image © 2009 John D. Furber. Used by permission."

Reference links:
1.    http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/radicals.html
2.    http://health.howstuffworks.com/life-stages/aging/antioxidant1.htm
3.    http://en.wikipedia.org/wiki/List_of_antioxidants_in_food
4.    http://www.squidoo.com/oprahcom-and-dr-oz
5.    http://websites.afar.org/site/PageServer?pagename=IA_bio_h
6.    http://legendarypharma.com/senescence.html#Mechanisms
 

Copyright ©2009 Joyce E.M. Wall