Life Extension and Antioxidants: An Overview

Mitochondria

Mitochondria: so powerful and so fragile.

 The question of whether dietary antioxidants can substantially delay death or senescence is important to both researchers and health enthusiasts. While supplementation is known to increase the average lifespans of test animals and to decrease certain mortality risks  in humans, they do not increase the maximum age of test organisms. They do not make Methuselahs out of mice or men. Denham Harman, the father of the original Antioxidant Theory of Aging, despairingly came to this conclusion when his experiments with several potent free radical scavengers, including butylated hydroxytoluene, failed to produce his desired outcome.

Evidence gleaned from the laboratory forced Harman to reformulate his original hypothesis: oxidative damage suffered by mitochondria, the powerhouses of cells, is responsible for the slowing of maintenance processes crucial to maintaining cellular and bodily integrity. While other organelles and even macromolecules can suffer in the same way, there are a number of reasons to focus on these organelles in particular: mitochondrial DNA does not repair itself as efficiently as the DNA residing in the cell’s nucleus, it is also located near the electron transport chain, which produces a constant stream of free radicals, and, lastly but perhaps most significantly from a practical standpoint, caloric restriction increases mammalian life span. It is conjectured it does this by reducing the mitochondrial workload, which in turn reduces the number of free radicals produced. This, as one can easily imagine, reduces the damage incurred by ATP generation. The question now becomes whether there are compounds that protect mitochondria in particular. Before turning to these still theoretical therapies, it is best to become acquainted with the tried and true molecules.

Ascorbic acid, better known as vitamin C, is famed for its proclivity to neutralize roving free radicals.  The relationship between heart disease and low vitamin C levels is well established. Men with the lowest levels of vitamin C have a 2.4 fold risk of dying from a stroke compared to those with the highest levels.  Likewise, protection from cancer and dementia has been demonstrated. Vtamin E displays similar properties. One of the most interesting properties of both E and C is the reduction of LDL oxidation and risk of atherosclerosis. Normal amounts of these vitamins and beta carotene can delay the onset of Alzheimer’s, but there seems to be no benefit to exceeding recommended allotments. Participants in a Dutch study with the lowest vitamin E intake were 70% more likely to develop the disease compared to the highest. It good to note here that those who consume nutritious foods the most often are likely health conscious in other ways, although researchers try their best to remove unwanted x factors. Large amounts of these vital molecules can have a prooxidant effect. In lab animals absurd amounts of E and C cut life short by 26%. Although, extra C and E appear to prevent mitochondrial damage after intense physical activity. This data may not translate directly to humans, but one must keep Paracelsus’s immortal maxim in mind: the dose makes the poison. Most people receive their fair share of both from their diets. Bagchi found that grape seed proanthocyanidin extract (GPSE) was 60% more effective. Dihydroquercetin, one of the flavonoids present in grape seed, synergizes with vitamin C by donating electrons back to the oxidized molecules. Dihydroquercetin and its relatives are receiving more attention than ever in their natural and extracted forms.

 Flavonoids hold a prominent place in the popular mind. Catechins, a type of flavonoid in tea, decreases oxidized LDL. This compounded with its calming qualities, is the likely explanation for its heart benefits. By volume tea contains considerably more flavonoids than fruits of vegetables. Those with the highest levels of flavonoid intake were the least likely to develop lung cancer, moreover, these compounds can inhibit tumorigenesis in its initiation and promotion stages. Many of these studies are done with large quantities of phytochemicals than a person would likely consume from unextracted plant material, but some meaning can be extrapolated from them. It is unclear as to how well, if at all, various flavonoids cross the blood brain barrier, yet in animal studies they appear reduce inflammation and to prevent cognitive decline. Midlife tofu consumption increases one’s risk for Alzheimer’s. It is likely something in the whole food, not the soy isoflavones themselves, that caused this unexpected result. This is yet another reason to stay away from soy products. The stilbenoid resveratrol has also captured the public’s attention in recent years. Most likely because it is found in red wine and, to a lesser extent, chocolate. Fueled by this, marketing and the then lauded research coming from the lab of Dipak Das, resveratrol, seemed poised to take center stage. Fortunately for science 12 of Dipak Das’s studies were found to be fraudulent. There is no evidence to support taking supplemental resveratrol for any reason. There is considerably more evidence for red wine itself, and although there is the possibility of overindulgence for those with alcoholic tendencies, an occasional glass of Mourvedre will likely do more good than harm.

Melatonin, a hormone critical to regulating circadian rhythms, is a powerful antioxidant which contributes to sleep quality, bone health, heart health and readily crosses the blood brain barrier. Melatonin improves symptoms in Alzheimers patients, possibly by protecting neurons from beta-amyloids. The importance of quality sleep is not disputed and surely some of the benefits melatonin provides come as an indirect consequence of its somnambulant powers. It is not a miracle drug; melatonin inhibits the secretion of testosterone and prolonged use could in theory shut down endogenous production. Further trials are required before the proper amount to take nightly is determined, likely this will be largely dependent on each person’s needs. In this case personalized medicine and cellular monitoring devices will be a boon. Glutathione (GSH) has been given a number of titles to denote its princely status among common antioxidants. Like melatonin it is made by the body and although it is used intravenously by medical professionals to treat infertility and side effects from chemotherapy, its efficacy when taken orally was and still is doubted. This erroneous and unfounded assumption has been debunked in studies with humans and rats.  While GSH deficiencies are linked with a number of diseases and increased mitochondrial damage, it is hard to say when or who requires supplementation without a blood test. It is also not known yet whether above average levels of plasma GSH delay senescence or not. Although the fact that additional GSH is linked with decreased mitochondrial wear and tear. It has even been proposed as a therapy for diabetics for this reason. Will there be a way to effectively eliminate mitochondrial deterioration without compromising the integrity of the whole organism?

The idea of targeting mitochondria is not entirely new. MitoQ, a modified ubquinone, has been through clinical trials. It was given to patients with advanced Parkinsons and to people with hepatitis C. Why this was done and who thought MitoQ would be of any use  to these sample groups is not clear. Predictably, the placebo and control groups in the Parkinsons study showed no difference. It showed some promise as a therapeutic for those with liver disease, but much more work needs to be done before MitoQ is hailed as the savior of humankind. Lipophilic cations and SS-peptides assist in shuttling the compound to the mitochondria. Members of the latter group may be useful in the treatment of heart disease, but it is still to early to say. Anything remotely related to anti-aging research, even if it has real and immediate medical applications, is shunned by the establishment which to this day considers biological aging, something that is neither universal nor inevitable, an irreversible consequence of the laws of thermodynamics. It is agonizing to endure such stupid arguments rooted more in folk wisdom than in hard science. It is even harder to endure more so when the sources for these proclamations do not come from the fringes but from the lofty peaks of the ivory tower itself. Within the next decade, however, these drugs are likely to experience an explosion in research and in use. A nearly universal solution to human disease with no drawbacks is simply too good to pass up. Such a compound will not cure death, but it will buy us all a little more quality time.

 

 

 

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