Ageing

Contents

Origin of Ageing

		shows that there is considerable deviation from a linear relationship, and Figure 02 displays many exceptions including the primitive sea anemone, which can survive up to 70 years. Signs of senility, or extreme old age, are seldom seen in the wild. Animals living under natural conditions rarely approach their maximum possible age because of very high death rates due to infant mortality, diseases, predators, bad weather, accidents, or competition for food and shelter. For this reason, most of the reliable information about the length of the life span comes from the zoos.
Figure 01 Life Span[view large image]	Figure 02 Bio-longevity[view large image]

There are three theories on the origin and evolution of ageing. They are not mutually exclusive. The combination actually provides a consistent hypothesis.


1. Mutation Accumulation - As mentioned above, most animals in the wild do not have the opportunity to reach senescence. Natural selection has no chance to operate on a wide range of alleles with late deleterious effects. They are allowed to accumulate over the generations with little or no check. Thus, the problems with senescence occurs only in modern human or animals in the zoos within an environment, where "life expectancy" of living organisms have been artificially extended. Life expectancy is the average (over the population) total number of years (or days, or hours) that an organism expects to live. It is fundamentally different from life span, which is the maximum time interval that an organism can live.
2. Antagonistic Pleiotropy^¶ - This theory suggested that pleiotropic genes with good early effects would be favoured by selection even if these genes had bad effects at later ages, i.e., a small beneficial effect early in life can outweight a late deleterious effect even if the latter results in senescence and death.
3. Disposable Soma - This theory suggests that organism will benefit by investing any spare resource into reproduction or survival, rather than into better repair capacity, even though this means that damage will eventually accumulate to cause ageing.

Ageing Process and Symptoms

		The ageing process occurs over all the body and for everyone, but the pace may be different depending on the type of organ or individual. Certain cells in our tissues simply stop working after a while. When enough tissue is rendered dysfunctional, we come face to face with the debilitation of ageing. However, these cell deaths do not happen all at the same time. Some tissues remain viable for many decades, some wear out rather quickly. And ageing does not occur in the same way in every human being. It turns out that people's lifestyles also has additional influence on ageing. Table 01 lists the ageing symptoms for a few selected organs and biological functions to illustrate "how we age". Number inside the parenthesis indicates the age when ageing kicks in. More details can be found in Figure 03 and 04 for some of the organs.
Figure 03 Symptoms 1 [view large image]	Figure 04 Symptoms 2 [view large image]

Table 01 Ageing Symptoms

Table 02 Leading Causes of Death in the U.S.

Causes

Ageing is caused by the accumulation of damage to the cells. Some of the causes are unavoidable such as ultraviolet radiation, free radicals, and genetic effects; others involve environmental and behavioral influences. Figure 05a summarizes the major causes of ageing, and the consequences.



One characteristic shared by all species is the accumulation of unrepaired somatic damage. Thus, lifelong accumulation of various types of damage; along with random errors in bio-informational processes are the major causes of ageing. Interventions that remove damage might counter some of the adverse effects. But macromolecular damage comes in many forms, many of which have yet to be identified. It might seem more efficient to eliminate damaging molecules, rather than the damage itself. However, some damaging molecules are crucial for normal cellular function we cannot do without. Some time interventions are two edges sword. For example, tissue regeneration elevates cancer risk by increasing the chance

Figure 05a Causes of Ageing [large image]

of acquiring DNA mutations or epi-mutations. While tumour suppressor mechanisms either eliminate cells that acquired extensive damage (apoptosis) or permanently prevent their proliferation (senescence). When damage levels are not high enough to elicit an apoptotic

or senescence response, a potentially more serious situation ensues that is difficult to counter: the gradual accumulation of random changes in DNA or protein, turning tissues into cellular mosaics. Such stochastic (random) changes can reset gene regulatory loops, and randomly alter gene expression patterns on a cell by cell basis. These changes, in aggregate, might compromise tissue function, without eliciting immediate cellular responses. Stochastic gene regulatory drift would be difficult to correct. Followings are more detailed descriptions for some specific causes.



DNA Damage - Usually DNA damages (such as from uv light) are corrected by repair enzymes. When the repair mechanism breaks down, it causes a progressive process in ageing, in many age-related diseases like cancer and in genetic diseases such as Down´s syndrome, cystic fibrosis and Werner´s syndrome. People with DNA repair disorders often have broken chromosomes, following exposure to ionizing radiation or chemicals that affect cell division. Figure 05b depicts two processes to repair DNA damage inflicted by UV light, which causes an extra covalent bond to form between adjacent pyrimidines, particularly thymines. The emzymes called photolyases absorb energy from visible light and

Figure 05b DNA Repair [large image]

use it to detect and bind to pyrimidine dimers, then break the extra bond.

• Free Radicals in Metabolism - Even though if cellular damage by external causes can be avoided, an inherent problem is bound to arise by internal metabolism. The metabolic pathway in mitochondria relies on the transportation of free electrons, which eventually attach to oxygen and are normally neutralized by hydrogen ion to form water. This is usually referred to as respiration. Sometimes the process breaks down; the electrons do not attach to the oxygen and instead, attach to other oxygen species. Specific molecules, each carrying a wayward electron, were created. They are call free radicals (such as hydroxyl, superoxide and peroxide - collectively called reactive oxygen species or ROS, Figure 06a). These free radicals are highly reactive and can do tremendous damage to the cell. The ROS can indiscriminately damage anything that gets in their way - proteins, fats, RNA, and DNA. The effect is cumulative and a serious problem will occur if ROS numbers get too high. Not surprisingly, the cell has responded to this threat by creating various enzymes that bind to free radicals and inactivate them. Collectively, molecules that destroy free radicals are called anti-oxidants.

  		Aging is probably the result of the breakdown in the cellular safety nets - not enough anti-oxidants are produced naturally. In addition, modern life has enormously increased the number of toxic free-radicals introduced into our bodies every day from the surrounding environment. The most significant sources of excess free-radicals are dietary or environmental. Dietary sources are usually fats, either rancid or hydrogenated fats, and fats that have been heated to high temperatures during cooking. Environmental pollutants include automobile exhaust, cigarette smoke and numerous other chemicals, physical exercise, stress, and radiation. Table 03 summarizes the variety of defenses prevent or repair molecular damage caused by free radicals, but as a group they are thought to be imperfect. Some evidence indicates that certain of the defenses also become less effective over time (ageing). New study found that in the course of ageing, certain people are more vulnerable than others to age-related
  Figure 06a ROS [view large image]	Table 03 Defenses [view large image]	damage from ROS, and genes related to memory and learning appear to be more vulnerable than other genes. Further research is needed to identify the causes.

  Lately in 2008, it is suggested that drinking or eating isotopes can slow down the chemical reactions with ROS. It is because the heavy isotopes form stronger covalent bonds than their lighter counterparts. While the effect applies to all heavy isotopes, including those with the elements of life such as carbon-13, nitrogen-15 and oxygen-18, it is most marked with deuterium (heavy water with one extra neutron) as it is proportionally so much heavier than hydrogen. Deuterated bonds can be up to 80 times stronger than those containing hydrogen (Figure 06b). The idea has been tested on fruit flies. It is found that large dosages were deadly, smaller quantities increased lifespans by up to 30%, and herein lies some problems with this big idea:

  Figure 06b ROS Damage Control [view large image]

  • Safety - Although carbon-13 and the other elements of life seem to be essentially non-toxic, the tolerant limit for deuterium in mammals is at about the 20% mark, and at 35% it becomes lethal.
  • Cost - The current market price for deuterium is about US$300 per liter - much more expensive than gasoline. Method is available to extract deuterium from water, but there is no incentive to produce them in bulk.
  • Delivery - Another problem is to deliver the isotopes to the specific sites. Something called "ifood" has been developed to do the job. It adds the isotopes to the essential amino acids not produced by the body, the reinforced amino acids will thus incorporate into the proteins. Another possibility is to feed deuterated water or isotope-enriched amino acids to farm animals.
  • Ageing Causes - It is now understood that ageing has multiple underlying causes. Free radical damage alone cannot account for all the biological changes that happen with old age. It is doubtful that drinking deuterium laced water alone would stop ageing altogether.
  
  
• AGEs (Advanced Glycation End products) - Another prominent causes of somatic damage is related to "reducing sugars", which react with carbohydrates and free amino groups, resulting in difficult-to-degrade AGEs. They accumulate in long-lived structural proteins, such as collagen and elastin increasing the stiffness of blood vessels, joints and the bladder, and impairing function in the kidney, heart, retina and other organs.




Telomere - The telomeres lie at the tips of the chromosome. They have hundreds to thousands of repeats of a specific 6-nucleotide DNA sequence. The telomeres lose 50 to 200 of these nucleotides at each mitosis; gradually shortening the chromosome. After about 50 divisions, a critical amount of telomere DNA is lost, which somehow signals the cell to stop mitosis. The cell may remain alive for a while but is unable to divide further. Some have likened the process of telomere shortening to a genetic biological clock that winds down over time. Today, researchers continue to probe the telomeric "timepiece," hoping to better understand the aging process. For example, It is found that in yeast, the est1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senes-cence in higher eukaryotic cells. It is also found that the amount and length of telomeric DNA in human fibroblasts§ does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo. But it is not yet clear whether this loss of DNA has a causal role in senescence. Research in 2007 found the critical telomere length to be 12.8

Figure 07 Telomere etc. [view large image]

repeats long - any shorter and the chromosomes began to fuse together at their ends. Another study in 2008 found people who exercised vigorously 3 hours/week had longer telomeres and were biologically 9 years younger than people who did under 15 minutes.

It has been known for some time that the telomerase enzyme, which is present naturally in some mammalian cells, can prevent the telomeres from unraveling. One of the 2008 studies confirms that at least one type of human cell can indeed be restored to a youthful state by boosting telomerase levels. The other suggests that boosting telomerase can result in longer life in mice. The concerns are on its side effect in promoting the growth of cancer cells as well. It is proposed that the treatment to extend human lifespan could be combined with cancer drugs to offset any enhanced cancer risk. In short, we want the best of both worlds - allowing cell division to happen when we need it (in normal cells) but not to happen when we don't (e.g., in cancer cells).


• Program Death - Recent research in 2003 points to another biological clock, which determines the life span of an organism. It is found that although the yeast cell normally goes through about 30 cell divisions in its five-day life span, DNA errors in daughter cells started appearing 100 times faster than normal after about 25 cell divisions - the equivalent of middle age in humans. It is noticed that about 80 percent of cancers are diagnosed in people over 55. Since both yeasts and humans use similar mechanism for copying DNA, so the rapid accrual of mutations after midlife is probably not coincidental. It could have something to do with an accumulation of damaged proteins within the cell or with breakdown in the proteins that control DNA replication and repair or with damage in the DNA itself - there is no definite answer at this point. But there seems to be a powerful force in all cells that operates on its own clock with a predetermined expiration date. (The idea that ageing is programmed was missed by evolutionary geronotologists, who recognized that natural selection could not, and would not, bring about such a fate except in very special circumstances).



• The Genes of Ageing - Another recent research on ageing has identified a gene in the roundworm called daf-2. When this one gene is mutated (its function destroyed), the life span of the organism is doubled. This daf-2 gene can be considered a "master gene" of aging. This is because its protein can control the activities of many other genes. Its expression gradually shuts down the cellular repair mechanism as we aged. Cellular damages are inevitable; all multicelluar organisms eventually succumb to the exposure of chemicals, pathogen, extreme temperature and UV radiation because of the crumbling repair mechanism.



• Longevity Genes - Longevity is known to be primarily a matter of environment such as diet, smoking, ... Genetics are thought to contribute to only about 25-30% of the variation in survival to 85 years of age - roughly the average lifespan in developed countries. However, research in 2010 reveals that a cluster of 150 variants in DNA sequence can be used to predict (with 77% accuracy) whether a person has the genetic wherewithal to live to 100 year old. The key factor seems to be the ability to overcome the adverse effects rather than the absence of bad genes. Much more studies are needed to confirm this finding.



• Mitochondrial Theory of Ageing - Mitochondria are little pockets of energy within cells, shouldering the important task of converting food into usable energy forms. To meet demands, every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes, which encode a few mitochondrial proteins. This theory proposes that accumulation of mutations in mitochondrial DNA leads to progressive bioenergy deficiency, cellular damage, degeneration and eventually death. To test the theory, mice were genetically engineered to have

mtDNA polymerase with poor proof-reading activity, and hence an enhanced mutation rate. These mice develop signs of premature ageing and die aged about a year instead of 2-3 years. The finding strongly support the idea that mutations in mitochondrial DNA can cause at least some features resembling ageing instead of just correlative (the manifestations of growing old). Figure 08a compares the mutating mice (mut) with the littermate wild-type (wt) at the age of ~ 40-45 weeks. It shows the mtDNA-mutator mice with reduced body size, kyphosis (curving of the spine), reduced hair density and different stages of alopecia (baldness) - delineated by dashed line (from bottom to top).

Figure 08a Mutating Mice [view large image]

New study on human have linked unhealthy mitochondria to Alzheimer's, Parkinson's, type 2 diabetes and other degenerative diseases.

It is reported in 2006 that a new method enables the determination of aging in different parts of the human body. It is found that the body's front-line cells endure the roughest life, last the briefest time and are constantly replaced - these include the epithelial cells lining the gut (five days), the epidermal cells covering the skin's surface (2 weeks). Figure 08b shows the average age of other types of cell (yellow circles); those indicate by red circles are still under investigation. Now if the skin is so young, why don't we retain a smooth complexion even into old age? The answer lies with the mtDNA, which accumulates mutations at a faster rate than DNA in the nucleus. In skin, for instance, mitochondrial mutations are thought to be responsible for the gradual loss in the quality of collagen, the skin's scaffolding, which is why skin loses its shape and forms wrinkles. If we ever find ways to protect or repair mtDNA, this new discovery means that we could significantly delay ageing.

Figure 08b Ageing

Reliefs

		keeping the body and mind active and by maintaining a sensible diet. The record holder of maximum longevity belongs to France's Jeanne Calment (see Figure 10), who lived to be 122 years and 164 days old. Longevity ran in her family. Calment's mother lived until she was 86 and her father until he was 94. Her personal outlook of life may also contribute; it is said that she was immune to stress. She was once quoted: "If you can't do anything about it,
Figure 09 Fountain of Youth [view large image]	Figure 10 Jeanne Calment [view large image]	don't worry about it."

Defence Against Free Radicals and Diets - To increase the defence against these ROS, it is suggested that consumption of special kinds of foods, herbs, and dietary supplements (including vitamins C and E, beta carotene and selenium) will scavenge excess free-radicals and provide raw materials necessary for the body to produce antioxidant enzymes. Many of the foods high in antioxidants are vegetable matter. Tomatoes, broccoli, cauliflower, peppers...are all excellent choices (Figure 11a). The key is to focus on eating those fruits and vegetables that have rich hues of color. These are high in what are known as phytonutrients. Phytonutrients are nutrients concentrated in the skins of many vegetables and fruits, and are responsible for not just their color, but scent, and flavor as well. Phytonutrients are the best antioxidant foods that exist in nature. Clinical trials are now revealing that phytonutrients can enhance the strength of the immune system, and may play a role in preventing certain cancers. Blueberries and bilberries are two

Figure 11a Vegetables [view large image]

of the best antioxidant foods you can buy -- and are very rich in phytonutrients.

Study in 2006 reveals that antioxidants are beneficial only from natural food sources. Double-blind randomised controlled trials indicated that supplements failed to pass the test time and again. At best, they are a waste of time and money. At worst they could be harmful. For examples, beta carotene supplement is found to increase the risk of lung cancer in smokers; vitamin C may accelerate atherosclerosis in some people with diabetes; vitamin E is clearly doing something, but it loses its antioxidant power inside the body. These vitamins are useful only in people with such deficiency already. No one knows for sure why the supplements do not work. One explanation argues that because the antioxidant in fruits and vegetables are bound into tough, fibrous material, they hang around in the stomach and colon, where they can neutralise free radicals. Figure 11b lists the top 20 antioxidant foodstuffs rated by the US Department of Agriculture in 2004. TE = Trolox Equivalents. Trolox is a vitamin E derivative which is used as the standard benchmark for antioxidant power. By way of comparison, 100g of wholegrain bread contains 1421 mol of TE.

Figure 11b Antioxidants [view large image]

Table 04 Link Between Foods and Genes

pH Level - Similar to the body temperature, which has to be maintained at 98.6^o F; the pH level in the various body fluids are kept at a narrow range (see Figure 12a) for the metabolic reactions to proceed properly. Figure 12b shows the pH levels for various substances (pH = 7.0 is neutral, pH < 7.0 is acidic, pH > 7.0 is alkaline). The Saliva pH test is a simple test to measure the susceptibility to cancer, heart disease, osteoporosis, arthritis, and many other degenerative diseases. In the saliva test (with pH paper), most children are dark blue (colour of the pH paper), a pH of 7.5; over half of adults are green-yellow, a pH of 6.5 or lower, reflecting the calcium deficiency of aging and lifestyle defects; cancer patients usually register bright yellow, a pH of

		4.5, especially when the disease becomes terminal. You can test the pH level of your saliva or urine at home with pH paper strips. Figure 12c shows the colour index for standard pH paper corresponding to the pH scale. An acidic pH can occur from, an acid forming diet, emotional stress, toxic overload, and/or immune reactions or any process that deprives the cells of oxygen and other nutrients. The body will try to compensate for acidic pH
Figure 12a Body Fluid pH Levels [view large image]	Figure 12b pH Scale	by using alkaline minerals. If the diet does not contain enough minerals to compensate, a build up of acids in the cells will occur. The body has three mechanisms for the maintenance of normal acid-base balance:

1. Rapid chemical buffering - The balance is restored by buffers in the blood. The buffers are supplied by withdrawing minerals from other organs including the bones, soft tissues, body fluids and saliva. This occurs almost instantly but buffers are rapidly exhausted, requiring the elimination of hydrogen ions to remain effective.
2. Respiratory compensation - This mechanism uses breathing to eliminate carbon dioxide (which produces acid). The respiratory center in the brainstem responds rapidly to changes in CSF (Cerebrospinal Fluid) pH (normally at 7.3). Thus, a change in plasma pH results in a change in ventilation within minutes.
3. Renal compensation - The kidneys respond to disturbances in acid-base balance by altering the amount of bicarbonate reabsorbed and hydrogen ions excreted. However, it may take up to 2 days for bicarbonate concentration to reach a new equilibrium.

Diet adds one more way to control the pH level.

Disturbance of the body's pH balance results in either acidosis or alkalosis. The dietary habit of most people tends to develop acidosis more often than alkalosis. They are prone to acquire diseases and symptoms that reflect the body's overly acidic state. Acute or emergency attempts to detoxify the body. The body may throw off acids through the skin, producing symptoms such as eczema, recurrent illnesses result from either the body trying to mobilize mineral reserves to prevent cellular breakdown or acne, boils, headaches, muscle cramps, soreness, swelling, irritation, inflammation, and general aches and pains. Chronic

symptoms show up when all possibilities of neutralizing or eliminating acids have been exhausted. Virtually all degenerative diseases, including cancer, heart disease, osteoporosis, arthritis, kidney and gall stones, and tooth decay are associated with excess acidity in the body. One of the solutions is to take foods that cause the blood to become alkaline. For example, almost all vegetables (except peppers, beets), and practically all fruits (except blueberries, plums, prunes, cranberries) are alkaline. Some dietitians recommand as much

Figure 12c Colour Index for pH Paper [view large image]

as 80% of the diet to be alkalizing foods. Many websites post complete listing on alkaline and acidic foods (see for example: http://www.essense-of-life.com/info/foodchart.htm). A comparison of the pH food chart with the list of antioxidants (Figure 11b) shows that high

Recently in 2004, it is found that the activity level of skeletal muscle modulates a range of genes, which produce dramatic molecular changes - and keep us healthy. The skeletal muscle is the largest single tissue type in the human body. We have more than 640 muscles, accounting for between 30 and 40 precent of total body weight. It uses as much as 25% of the energy consumed by the body at rest. Skeletal muscle continuously adjusts its composition to meet the acute or chronic demands placed on it - a process called plasticity. It has been shown that one-third of skeletal muscle in an immobilized limb can disappear within weeks. It is as if skeletal muscle recognizes that it is not needed and

Figure 12d Exercise and Gene Expression [view large image]

"remodels" itself into weak muscle. In order for skeletal muscle to exhibit plasticity, specific genes in the muscle sense the change in its usage and respond by altering the quantities of

Meditation - Meditation has been practiced in the East for thousand years and emerges in Western culture lately in various forms. If the mystical layers are removed from its traditional package, the net effect becomes very useful for reducing stress. The switch from "fight and flight" mode to maintenance mode would enhance greatly the health of everyone especially the elderly. It is known that most cells in the body store a large portion of the glucose and other nutrients in the form of glycogen or fat to serve as reserves for future energy demands. However, cells in the brain act differently. They burn up nearly all the fuel almost the moment it arrives. Such process requires a constant, uninterrupted flow of oxygen, and few if any of the nutrients

		are stored for future use. Thus, brain cells are always living on the edge, and never relax. The benefit of meditation is to allow the brain a moment of rest. During meditation the brain would have a chance to repair damages to the cells and to flush out waste from within the cells. Other beneficial effects include the improvement of the immune system for fending off diseases. Figure 13 and 14 show a standing and a sitting posture for the "simplified" meditation. It is not important whether the practitioner is standing, sitting or lying down. The most important requirement is to relax both the mind and the body. Initially it may be necessary to find a quiet place to minimize distraction. Eventually the mind learns to detach from the noise and other external stimuli. The effect also shows up in daily life. For example, there
Figure 13 Meditation, Standing [view large image]	Figure 14 Meditation, Sitting [view large image]	would be more tolerant toward alien beliefs, obnoxious behaviors, and other unpleasant happenings; it would also improve mental alertness and physical fitness.

Nicoyan Peninsula in Costa Rica - Men in Nicoya live to age 100 four times as often as men in the United States — even though their medical care costs only about 7 % as much. Sardinia - In this mountainous Italian island of Sardinia, farmers work hard in the fields, drink red wine, eat fruits and vegetables they grew themselves, and are taught to respect their elders. Okinawa - There is no word for "retirement" on this island. Men there have a fifth as much cancer as Americans, and a quarter as much heart disease. Loma Linda in California - It is about an hour's drive east of Los Angeles. Why should

Figure 15 Longevity Hotspots [view large image]

one city stand out amid the sprawl of Southern California? Perhaps, said researchers, because the Seventh Day Adventist Church there gives people a powerful sense of community.

Anti-ageing Research

• Anti-ageing Genes - Evolutionary theory and some crude experiments suggest that hundreds of genetically determined biochemical pathways (cascades of molecular interaction) influence longevity. It is relatively easy to prolong life span - in worms, at least - by changing hormone levels and enhancing the effects of fewer than 100 genes. Some of the target genes produce antioxidants; some make natural microbicides; some are involved in transporting fats throughout the body, and some, called chaperones, "keep the cell components in good working order". This kind of finding has opened the door for a neutraceutical company, Elixir, which is trying to develop a drug that would yield the same kind of results for humans (as in worms).



• Anti-ageing Alleles - A useful way to find alleles that might affect ageing would be to compare the genetic makeup of normal animals and of those displaying deferred ageing. Scientists will not only have to identify hundreds or thousands of alleles that occur most frequently in long-lived subjects, they will also have to decipher the biological functions and unique features of the corresponding proteins. The collected technologies needed to perform these tasks fall under the rubric of "functional genomics", which is very much a work in progress.



• Calorie Restriction without Dieting - It is known that calorie restriction can prolong life span in yeast, fruit flies, and mice by 70%. In fact, calorie restriction is an extremely effective strategy for survival during lean times, when it's an imperative, not a choice. The organism then waits till the end of the famine, then goes on to reproduce again. But since few people particularly want to limit their calories drastically. Scientists are searching for a pill that will have the same effect without dieting. A company called Sirtris is expected to get the drugs into clinics by 2010.



• New Anti-ageing Supplements - It is found that the combination of two chemicals - the acetyp-L-carnitine and alpha-lipoic - normally found in the cells (and also sold separately as nutritional supplements) can promote the performance of rats on problem-solving and memory test. These rats also moved around with more ease and energy. Researchers determined that the combination of these chemicals had improved the function of mitochondria, which serve as a cell's main energy source. A company called Juvenon plans to begin human trials soon to evaluate the cognitive effects of the dual supplements. Other chemicals such as lipoic acid is found to protect human tissue culture from oxidation when iron or hydrogen peroxide was added. The same company will try to replicate the result in human subjects. The goal of these researches is to add a few more years to people's lives.



• Interventions Testing Program - Currently in 2009, three different US institutions - the University of Texas Health Science Center in San Antonio, the University of Michigan in Ann Arbor and the Jackson Laboratory in Bar Harbor, Maine - are running drug tests for prolonging lifespan. These drugs include:
  1. Rapamycin - a drug used to suppress the immune system is found to be mimicking the effects of dietary restriction.
  2. Resveratrol - a compound found in red wine and thought to have beneficial effects on the heart.
  3. Simvastatin - one of a family of compounds called statins, also used for heart conditions.
  

References

• Theories of Ageing, a Summary -- http://mcb.berkeley.edu/courses/mcb135k/BrianOutline.html
• Theories of Ageing, in Details -- http://longevity-science.org/Evolution.htm
• Ageing -- http://www.niapublications.org/pubs/portfolio/html/biology.htm
• Longevity -- http://www.bio-itworld.com/archive/011204/youth_sidebar_4099.html