The Collison Newsletter August 2010

  

                                      TELOMERES*  

 

A telomere is a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from deterioration. Its name is derived from the Greek nouns telos end’ and meros part’.

History 

Dr Elizabeth Blackburn, from 1975 to 1977, while working as a postdoctoral fellow at Yale University with Joseph Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends. Their work was published in 1978. The telomere shortening mechanism normally limits cells to a fixed number of divisions, and animal studies suggest that this is responsible for aging on the cellular level, and sets limits on life-spans. Telomeres protect a cell’s chromosomes from fusing with each other or rearranging, so cells are normally destroyed when their telomeres are consumed. Most cancer cells are the result of ‘immortal’ cells which have ways of evading this programmed destruction.

 

Elizabeth Blackburn, Carol Greider and Jack Szostak were awarded the 2009 Nobel Prize in Physiology and Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.

Telomeres 

The DNA molecule of a typical chromosome contains

·      a linear array of genes (encoding proteins) interspersed with

·      much noncoding DNA.

 

Included in the noncoding DNA are

·      long stretches that make up the centromere and

·      long stretches at the ends of the chromosomes, the telomeres.

 

Telomeres are crucial to the life of the cell. They keep the ends of the various chromosomes in the cells from accidentally becoming attached to each other.

 

Elizabeth Blackburn compared telomeres to the plastic tips on the ends of shoe laces that keep them from fraying. An apt description!

 

During cell division, the enzymes that duplicate the chromosome and its DNA cannot continue their duplication all the way to the end of the chromosome. If the cells divided without telomeres, they would lose the ends of their chromosomes, and the necessary information they contain. The telomeres are disposable buffers blocking the ends of the chromosomes and are consumed during cell division and replenished by the enzyme telomerase.

 

Telomeres are strong markers for aging.

 

Not only do telomeres shorten as we age, over time they can become damaged and shorten because of inflammation, inhaled pollution including smoking, obesity and lack of exercise.

 

The telomere length is measured in ‘base pairs’ (bp). A ‘base pair’ is two nucleotides on DNA strands that are connected via hydrogen bonds. The size of an individual gene, the length of a chromosome and the length of a telomere are measured in ‘base pairs’. Hence the number of total base pairs is equal to the number of nucleotides in one of the strands (DNA is double-stranded). The human genome (23 chromosomes) is estimated to be about 3 billion base pairs long and to contain 20,000-25,000 distinct genes.

 

An oft repeated graph in the literature on telomeres shows that the telomeres’ length declines in dividing cells as we age:

·      At birth      - 8000 bp

·      At age 35  - 3000 bp

·      At age 65  - 1500 bp

 

It is estimated that human telomeres lose about 100 base pairs from their telomeric DNA at each mitosis (cell division). This would indicate why somatic (body) cells are limited in the number of mitotic divisions before they die out.

 

The enzyme telomerase slows this process and so extends the life-span of the cells.

Telomerase 

Telomerase is an enzyme that adds telomere repeat sequences to the end of DNA strands. It is in fact what is called a ‘reverse transcriptase’, synthesising DNA from an RNA template.

 

In the laboratory, when normal somatic cells are transformed with DNA expressing high levels of telomerase, they continue to divide by mitosis long after ‘replicative senescence’ (cell death) should have set in. And they do so without shortening their telomeres. This would suggest strongly that telomerase and the maintenance of telomere length are the key to cell immortality.

Accelerated Shortening of Telomeres 

As stated above, telomeres shorten with age.

 

Telomeres are highly susceptible to oxidative stress, responsible for the formation of free radicals which increase the rate of shortening. It has been shown that people with oxidative stress-related diseases have low levels of the antioxidant glutathione.

How to Delay the Shortening of Telomeres

1)      Glutathione 

Glutathione is an antioxidant produced by the cells of the body.

 

Glutathione is known to increase the integrity of telomeres. Increasing levels of glutathione may lead to some degree of reverse aging.

 

Glutathione is not a compound that can be ingested directly. It is manufactured inside the cell from its precursor amino acids glycine, L-glutamic acid and L-cysteine. It is a tripeptide. It is also known as gamma-glutamylcysteinylglycine or GSH. Cysteine is a sulphur containing amino acid and is responsible for the biological activity of glutathione. The availability of cysteine is the rate-limiting factor in glutathione synthesis by the cells. Cystine consists of two cysteine molecules that are joined together.

 

It is possible to increase the levels of glutathione by change in diet to one which is rich in the sulphur-containing amino acids that the cells need in order to synthesise glutathione. There are two sulphur containing amino acids, cysteine and methionine. The body manufactures cysteine from the essential amino acid methionine, and cysteine can also be found in most high-protein foods such as cottage cheese, yoghurt, red and white meats and oats. Methionine food sources are meats, beans, garlic, lentils, fish, eggs, yoghurt, onions and seeds. Whey protein and egg albumen are excellent sources of the sulphur containing amino acids, and either can be taken as a supplement.

2)      Exercise 

Multiple articles, book after book, the media and all health professionals tell us that exercise it good for us. It will make our hearts stronger, keep our brains sharper, reshape our bodies and keep depression away. It is one of the recommendations for the prevention of cancer (see my March 2008 newsletter Prevention of Cancer). It is one of the seven requirements for health as listed in my book How to Stop Feeling So Awful (see homepage).

 

In a recent study in the UK, over 20,000 healthy men and women, aged 45-79, were followed for an average of 11 years. Each person in the study was given a point for each of four healthy behaviours:

·      not smoking

·      exercising

·      moderate alcohol intake

·      eating at least five servings of fruit and vegetables a day.

 

The fruit and vegetable intake was verified by measuring the participants’ plasma levels of vitamin C.

 

At the end of the 11 years the authors looked at who had died, and compared those who were doing all four healthy behaviours with those who were not doing any of them.

 

Those with a score of zero were four times more likely to die (especially from cardiovascular disease) than those with a score of four.

 

The authors concluded that a person practicing none of the four healthy behaviours (with a score of zero) has the same risk of dying as a person practicing all four behaviours who is 14 years older.

 

Exercise, eat at least five servings of fruits and vegetables a day, have a little alcohol (perhaps as a nightcap) and don’t smoke and expect to live an extra few years.

 

Why is exercise beneficial? The following study links exercise to telomeres.

 

Research published in the Archives of Internal Medicine (2008) compared the length of leukocyte telomeres (as a marker of aging) between twins who exercised and those who did not exercise. Twins were chosen because they share much of the same DNA and were reared in similar environments as children. It was found (based on their telomere length) that those who exercised were biologically younger than those who did not exercise. Those who exercised the most, doing more than three hours of vigorous activity at a time, had the longest telomeres, which, when compared to the non-exercising twin, made them 10 years younger than their twin.

 

From these two studies and the vast literature advocating exercise for health, exercise is an essential for health and longevity.

3)      Omega-3 Fatty Acids 

It is well accepted that we need Omega-3 fatty acids for health, at the same time lowering the intake of Omega-6 fatty acids.

 

In brief, Omega-3 fatty acids:

·      are anti-inflammatory (counteracting inflammation)

·      are antithrombotic (prevent formation of blood clots)

·      prevent age-related cognitive decline

·      lower triglyceride concentration in the blood

·      lower blood pressure

·      slow age-related macular degeneration of the eye

·      maintain elasticity of arteries and improve endothelial function (a major factor in promoting growth of new blood vessels)

·      protect against depression

·      are necessary for foetal and infant brain development.

 

A recent publication in the Journal of the American Medical Association (JAMA), 2010, shows the link between Omega-3 fatty acids and the length of telomeres. The research was done at the University of California, where 608 outpatients with stable coronary heart disease were followed for 5-8 years. At the commencement of the study the levels of Omega-3’s and the length of the leukocyte telomeres were measured and again at the end of the observational period.

 

The lead researcher, Dr Ramin Farzaneh-Far commented on the findings as follows:

“The main result from our study is that patients with high levels of Omega-3 fish oil in the blood appear to have a slowing of the biological aging process over five years as measured by the change in telomere length.

 

Patients with the highest levels of Omega-3 fish oils were found to display the slowest decrease in telomere length, whereas those with the lowest levels of Omega-3 fish oils in the blood had the fastest rate of telomere shortening, suggesting that these patients were aging faster than those with the higher fish oil levels in the blood.

 

By measuring telomere length at two different times we are able to see the speed at which the telomeres are shortening and that gives us some indication of how rapidly the biological aging process is taking place in these patients.”

 

This study is just one more piece of evidence that shows how lifestyle choices can affect telomere length, promote health and delay aging.

4)      Diet and Lifestyle Changes 

A small study published in The Lancet Oncology by Dr. Elizabeth Blackburn and Dr Dean Ornish (2008) showed that Dr Ornish’s healthy lifestyle program could lead to an increase in telomerase levels.

 

Dr Dean Ornish is the Head of the Preventive Medicine Research Institute in Sausalito, California. He has, for decades, advocated diet to prevent diseases, especially heart disease.

 

This was a limited pilot study that looked at 30 men with low-risk prostate cancer who followed Dr Ornish’s program for three months.

 

Telomerase levels were measured as baseline and again after three months.

 

This group of 30 men:

·      ate a diet rich in fruits, vegetables, whole grains, legumes and soy

·      limited the fat content of their diet to a very low 10% of the total calories

·      kept the diet low in refined sugars

·      took vitamin supplements and fish oil (for Omega-3 fatty acids)

·      exercised moderately for 30 minutes each day

·      participated in an hour of a daily stress-reducing activity, like meditation or yoga and breathing exercises.

 

After three months it was found that, in the 24 participants with sufficient data for analysis, telomerase in the blood had increased by 29%.

 

The importance of telomerase has been set out above. This study shows that it is possible to protect telomeres with diet and a healthy lifestyle.

Conclusion 

The comments by Dr Dean Ornish and co-workers, in the above publication, are a fitting conclusion to this newsletter:

 

“The implications of this study are not limited to men with prostate cancer. Comprehensive lifestyle changes may cause improvements in telomerase and telomeres that may be beneficial to the general population as well.”

 

*Copyright 2010: The Huntly Centre.

Disclaimer: All material in the Huntlycentre.com.au website is provided for informational or educational purposes only. Consult a health professional regarding the applicability of any opinions or recommendations expressed herein, with respect to your symptoms or medical condition.

    

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