The only method proven to slow aging and extend lifespan in mammals is caloric restriction of a nutrient-rich diet, which has been demonstrated to work in rats, mice, and is now being studied in monkeys. While some people practice caloric restriction as a means of extending lifespan, its primary value is as a model to explore how aging can be controlled. Although none of the therapies in this section have been proven to retard aging, there is suggestive scientific evidence that they may have this ability. The Life Extension Foundation has launched two major, long-term research programs -- The Lifespan Project and The Rejuvenation Project -- aimed at developing evidence to determine if supplemental drugs and nutrients can slow aging and extend lifespan.

Deprenyl is another chemical name for Selegiline hydrochloride. It is available in the U.S. under the name Eldepryl. It is also available by mail from offshore companies. In a number of clinical trials, deprenyl has improved the condition of both Parkinson's and Alzheimer's disease. In controlled studies, however, its long-term use for Parkinson's disease was called into question. Evidence that deprenyl may slow aging includes studies showing it protects brain neurons from neurotoxins (in tissue culture), elevates levels of antioxidant enzymes, reduces levels of the dopamine-degrading enzyme monoamine oxidase-B, and extends the lifespan of both mice and rats.

Human Growth Hormone

Human growth hormone helps maintain the immune system and builds youthful muscle power and strength. Growth hormone levels decline progressively with advancing age. Scientists have demonstrated that restoring youthful levels of growth hormone via regular injections can rejuvenate aging men and women. A provocative study at North Dakota State showed significantly greater survival than controls among elderly mice receiving growth hormone injections. This study was not carried through to completion because the researchers ran out of growth hormone. To help assess the anti-aging potential of growth hormone, the Life Extension Foundation, as part of its Rejuvenation Project, will soon be funding a lifespan study of the effects of growth hormone on aging mice at the University of California at Riverside. Another method of boosting growth hormone levels is to take growth-hormone-stimulating nutrients such as arginine and ornithine. Several pharmaceutical companies are developing oral secretogogues, which stimulate growth-hormone-releasing-hormone, the pituitary factor that induces growth hormone release.

DHEA

DHEA (dehydroepiandrosterone) is an adrenal hormone that is the precursor for steroid hormones such as testosterone and estrogen. DHEA declines precipitously with advancing age in both men and women. There have been many studies showing that oral DHEA can improve neurological function, immune function, stress disorders, and that it can be protective against some types of cancer and cardiovascular disease. In one clinical study at the
University of California at San Diego, 50 mgs a day of DHEA taken daily over a 6-month period increased lean body mass and muscle strength and the perceived physical and psychological well-being of both men and women. One lifespan study with DHEA has been conducted in mice at a major university. Verbal reports indicate that DHEA was not successful in extending lifespan, but the results of that study have not yet been reported.

Melatonin

Melatonin is a hormone produced by the pineal gland, which is located beneath the brain. Melatonin is a highly potent antioxidant, which has been described as the pacemaker of the aging clock in humans. It is released every night as part of our time-dependent biorhythms to help induce sleep and recuperation from fatigue. Melatonin has been shown to have anti-cancer effects. In animal studies in Italy, melatonin and transplants of pineal gland tissue from young animals extended the lifespan of old animals, however the mice used in these studies had suboptimal lifespans. The Life Extension Foundation is funding a study to further assess the effects of melatonin on aging and lifespan in mice.

Acetyl-L-Carnitine

Acetyl-L-Carnitine (ALC) is an energy-stimulating compound similar to an amino acid. It has been shown to improve cognitive function in both normally aging individuals and Alzheimer's patients, and to strengthen the heart muscle. The basis for theorizing that ALC may be able to slow aging comes from evidence that ALC improves mitochondrial function in several ways. Mitochondria are the power plants of the cells, where energy for all life processes is generated. Scientists have speculated that the decline in mitochondrial function may be a cause of aging in humans. The effects of ALC on aging and lifespan are being tested as part of The Lifespan Project.

Coenzyme Q10

Coenzyme Q10 (CoQ10) is a cardioprotective, energy stimulating compound that has been shown to be effective as a means of preventing and treating certain forms of cardiovascular disease and cancer. In a study by Bliznakov, the lifespan of mice was increased by 50% by injections of CoQ10. In another study at UCLA Medical Center, the mean but not maximum lifespan of mice was increased by very high oral doses of CoQ10. In both studies, mice receiving CoQ10 looked especially good and healthy at advanced ages. CoQ10 is being assessed further for its effects on aging and lifespan in mice as part of The Lifespan Project.

Alpha Lipoic Acid

Alpha Lipoic Acid, also known as Lipoic Acid, is a highly potent antioxidant that counteracts reactive free radicals in the mitochondria, the power plants of cells where energy for all cellular activities is generated. Some scientists believe that mitochondrial free radicals play an important role in human aging, and have theorized that extra amounts of free-radical inhibiting compounds such as Alpha Lipoic Acid may be able to slow aging. Alpha Lipoic Acid is also effective in recycling other antioxidants such as Vitamin E back into their original form after they detoxify free radicals. There also is evidence that Alpha Lipoic Acid can reduce glycation damage due to excess glucose in the blood, which may be involved in aging, and that it can improve patients with diabetes, which has been described as an accelerated form of aging. The effects of Alpha Lipoic Acid on aging and lifespan in mice are currently being studied in The Lifespan Project.

Cysteine and Procysteine

Cysteine is a nonessential sulfur amino acid used for protein synthesis. An early study in Romania showed that Cysteine could extend the lifespan of laboratory animals, but there has been no follow-up to this study. Procysteine is a modified form of Cysteine that is believed to be safer and more potent than Cysteine. Both Cysteine and Procysteine play a role in the synthesis of glutathione, a potent antioxidant found in every cell of the body, which is involved in folding proteins into their correct structure, and which declines in concentration with advancing age. The effects of Procysteine on aging and lifespan in animals is being studied in The Lifespan Project.

NADH

NADH is a form of nicotinamide adenine dinucleotide, a coenzyme that assists enzymes involved in energy production within mitochondria, the power plants of the cell. NADH plays an important role in the generation of ATP (adenosine triphosphate), the body's energy currency, and has been found to be effective in Europe in treating Parkinson's and Alzheimer's disease. NADH is also needed for the regeneration of glutathione after it has become oxidized. The Life Extension Foundation has funded a study to examine the effects of NADH on aging and lifespan in mice.

Lycopene

Lycopene is a member (along with beta-carotene) of a family of plant pigments called carotenoids. There are more than 600 different carotenoids, but lycopene and the carotenes are the most important ones. They are the pigments that give leaves, tomatoes and other plants their bright colors. Lycopene is the best anti-aging candidate of this class of compounds because it is the most efficient quencher of an especially dangerous free radical called singlet oxygen. Equally important is the fact that lycopene is regenerated after quenching singlet oxygen, and can then detoxify dangerous molecules without being destroyed. Lycopene levels drop off with age, even if we continue eating the fruits and vegetables that contain it. Lycopene has been shown to increase the survival of irradiated mice, and to decrease the incidence of various types of cancer in mice. It is now the subject of study in The Foundation's Lifespan Project.

Vitamin E

Vitamin E is the major fat-soluble compound that protects our cell membranes against oxidative damage. It can break the self-perpetuating chain of oxidative reactions in unsaturated fatty acids in membranes. Vitamin E also helps maintain the antioxidant activity of Selenium, and works with this trace mineral to help boost immune function. There have been highly persuasive studies in humans showing that regular Vitamin E intake can reduce the risk of heart attacks in both men and women, and that it can protect us from several types of cancer. In one study, the combination of Vitamin E and Vitamin C reduced death from all causes. Vitamin E is being studied for its effects on aging and lifespan as part of The Lifespan Project.

Vitamin B5 (Pantothenic Acid)

In 1958, biochemists Roger J. Williams and Richard Pelton fed large amounts of Vitamin B5 to male and female mice. They found that the treated mice lived an average of 19% longer than controls. A previous study had found that B5 increased the lifespan of fruit flies. The major biochemical role of Vitamin B5 appears to be as a constituent of Coenzyme A, which is involved in many chemical reactions essential to life, including the detoxification of many dangerous substances. When high doses of Vitamin B5 were given to rats they were able to survive in cold water twice as long as controls. Similar results have been found in humans.

Vitamin B6 (Pyridoxine)

In an experiment conducted at NASA's Ames Research Center in a long-lived strain of mice already in middle-age (18 months of age), the scientists found an 11% increase in lifespan in animals fed Vitamin B6 compared to controls. Vitamin B6 plays an important role in many life processes. It is needed for the metabolism of amino acids such as tyrosine and phenylalanine, and is an essential co-factor (along with Vitamin B6 and folic acid) in the body's defense against elevated homocysteine levels, which have been linked to arteriosclerosis, heart disease and stroke.

Synthetic Antioxidants

In the 1950s and 60s, Denham Harman of the University of Nebraska Medical Center, the originator of the free radical theory of aging, conducted a series of experiments in which he extended the lifespan of short-lived mice with various synthetic antioxidants. The antioxidants included BHT (butylated hydroxytoluene), Ethoxyquin (dihydroethoxytrimethylquinolone), 2-mercapto-ethylamine (2-MEA), and NDHGA (nordihydroguaretic Acid). Dr. Harman found mean lifespan increases of up to 61% with these compounds. Subsequent studies confirmed the lifespan-extending ability of Ethoxyquin and NDHGA. These supplements have never become popular because of concern about adverse effects from their chronic use.

Levodopa (L-Dopa)

In 1977, George Cotzias, et al. reported a 50% increase in the mean lifespan of rats fed very high doses of L-Dopa, the precursor to the neurotransmitter dopamine. In another study in rats, it was shown that the incidence of movement disorders among aged rats were almost totally reversed by L-Dopa, which enabled the rats to swim almost as well as young rats. L-Dopa is used to treat Parkinson's disease patients, with major improvements usually occurring for several years followed by a steep decline in function coupled with adverse side effects. The problem with L-Dopa as an anti-aging drug is its side effects at high doses, which include abnormal heart rhythms, movement disorders, mental disturbances, and a greater risk of at least one type of cancer.