Tag: aging

An end to the old weakling

Claus Hancke

July 14, 2006

The deficiency of an important antioxidant enzyme seems to be the most important reason that the elderly develop weak muscles. This paves the way for interesting perspectives.

The most striking sign of aging is that muscle strength is reduced and movement becomes slower. Even the most persistent exerciser cannot avoid it. The weakening of the muscles is the most important reason that old people become frail.

Why does this happen? We know that with age more and more signs of oxidation by free radicals can be found in muscles and other tissue. But is this why the muscles weaken?

A group of 12 researchers from both Texas and Stanford University in U.S.A. have undertaken an unusual and very detailed study which indicates that this is precisely the reason. According to them, the age related muscle weakness is due to strain from free oxygen radicals. This can shine light on possible ways to slow this process and maintain mobility longer.

Aging mice are a reliable model for age related muscle weakness in humans. But the American study was just possible because they had a special genetically manipulated mouse which lacked the ability to produce SOD (superoxide dismutase), a very important anti-oxidative enzyme.

In order to understand this it is necessary to know that free radicals are broken down in a chain reaction. SOD is necessary in the first step. In this step “active oxygen” (superoxide anions) is converted to less dangerous hydrogen peroxide. Without SOD this occurs very slowly, but with SOD this occurs at breakneck speed. In the next step hydrogen peroxide, which is also dangerous, is converted to harmless water. This occurs with the help of a selenium rich enzyme. This is one of the best known reasons that selenium, which we get too little of, is necessary for life.

Vital SOD
Back to SOD. It is also necessary to know that there are many forms of SOD. One of them is found in the mitochondria, which are the small power plants of the cells where cell metabolism occurs. If a mouse lacks SOD here, it dies after no more than three weeks. The power plants are destroyed by the free radicals which they produce. Another form of SOD is found outside the mitochondria, but still inside the cells. If the mice lack this type they can survive, but their lifespan is shortened by about 30%.

The researchers worked with mice which lacked the latter SOD form. They saw that the mice already started to develop weakened muscles while young. When the mice were 29 months old, they lacked half of their muscle mass in their hindquarters, whereas normal mice of the same age retain all of their youthful muscle. The so called fast type II muscle fibres were the most affected. The mice were left with slower type I fibres. Heart muscle remained undamaged.

The strength and speed of the muscles were not the only things affected. The mice also became less curious and less willing to engage in exhausting exercises like running in a mouse wheel. When they become old, they shook slightly in their weakened muscles.

It is hard to contest that this damage was caused by oxygen radicals. SOD has no other function other than being an antioxidant. As always it can be added that more research is necessary. This was only a study on mice. But if the results can be transferred to humans it can be argued that it is beneficial to increase the body’s production of SOD. SOD production is decreased with age.

Because SOD is an enzyme, which is to say a protein, it cannot be eaten without being destroyed in the stomach unless given as a special preparation. In combination with other antioxidants and possibly vitamin D (but that’s another story) the effect is supposedly more pronounced. This is not certain, but it is interesting.

By: Vitality Council

References:
1. Muller, Florian L et al. Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. Free Radical Biology & Medicine 2006;40:1993-2004
2. Jackson Malcolm J. Lack of CuZnSOD activity: A pointer to the mechanisms underlying age-related loss of muscle function, a commentary on “Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy”. Free Radical Biology & Medicine 2006;40:1900-01

Vitamins against aging

Claus Hancke

January 9, 2006

The need for many vitamins increases with age. A deficiency can be compared to radiation exposure, which causes mutations, decreased energy production, cancer, and age-related changes in the body, according to one of the World’s leading nutrition scientists.

When Bruce Ames was 70, President Clinton surprised him with U.S.A.’s highest scientific recognition, The National Medal of Science, for his research in nutrition, cancer, and aging.

Today he is 77, but still an almost incomprehensibility active researcher and professor at the famous Berkeley University in California. He is also the man behind the world renown Ames test, a lightning fast method to find out whether a specific chemical can cause mutations, and thereby cancer.

This introduction shows that Ames it a researcher to be listen to, and therefore we have decided to discuss one of Ames’s latest and most important scientific articles.

The article was published in a periodical for the European organization of molecular biologists (EMBO reports). It describes how it is possible to reduce the tendency for cancer and aging by taking more than the recommended dose of diverse vitamins and other important substances.

How does it do this? In his study Ames found that deficiencies of vitamins C, E, B6, and B12 as well as of folic acid and zinc can have exactly the same effect on cells as radioactivity. This means that such deficiency causes mutations, for example as a result of breakage of the chromosomes.

Folic acid deficiency causes such breakage because it leads to the introduction of a wrong substance (uracil) in uncountable places along the DNA molecules. These mutations affect the cells the same way as a virus affects a computer. In the worst cases, the system beaks down.

But deficiency does not only lead to mutations. Another result is weakening of the energy producing mitochondria, otherwise known as the cells’ power plants. In order for the mitochondria to function, they must have access to certain enzymes, which can be regarded as the power plant’s machinery. The enzymes work together so that the product from one “machine” is processed further by the next in a chain of reactions which result in the conversation of oxygen and hydrogen into water, and the production of energy. But where do the enzymes come from? Without the necessary building blocks they do not exist at all!

Ames has among other things proven that deficiencies of zinc or the B vitamins biotin and pantothenic acid weaken the fourth reaction in this chain of reactions. They are the building blocks of the “machines” which carry out this step in the process. Not only is the production of energy reduced by such deficiency, but oxygen is also insufficiently converted to water. As a result the mitochondria empty free radicals into the surrounding cell where they can cause mutations, cancer, and weakness.

More Energy
Why does Ames believe that it is necessary to take more vitamins than recommended? This is as a result of the third and last point in his thought process. It regards the consequence of the uncountable mutations which by the aforementioned methods unavoidably arise during ones life. These mutations cause the cells to produce less effective enzymes that bind less effectively to the vitamins which they need to aid their function. Ames maintains that this poor binding can be overcome simply by increasing the amount of vitamins. This makes the enzymes work again.

A particular problem in this regard is the weakening of the mitochondria which occurs with age. Without energy, nothing functions within the cell and the degeneration of the mitochondria is central to what we call aging. But Ames emphasizes that it is possible to make old rats faster by giving them supplements of the two vitamin-like substances lipoic acid and carnitine.

Both substances are important intermediates for energy production in the mitochondria. With age they bind poorly to the enzymes which cause the mitochondria to function poorly. But this poor binding can also be overcome with supplements. As well as making the rats faster it was possible to measure that their mitochondria once again functioned normally. Clinically such treatment has been able to result in improvement in people with mild Alzheimer’s.

The unique thing about Ames is that his arguments are based on biochemistry. This means that he refers to elementary chemical reactions which are demonstrable in the organism. Many others base their views of more or less uncertain clinical trails, sometimes without knowledge of the biochemistry behind them. It might not be coincidental that The Nobel Prise in medicine typically is given to a biochemist.

By: Vitality Council

References:
1. Bruce N Ames. Increasing longevity by tuning up metabolism. EMBO reports 2005;6:S20- S23.
2. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-a-lipoic acid. J. Liu et al. Proc Natl Acad Sci USA.2002;99:2356-61.
3. B N Ames et al. High-dose vitamins stimulate variant enzymes with decreased coenzyme-binding affinity (increased Km): Relevance to genetic diseases and polymorphisms. Am J Clin Nutr 2002;75:616-58.