Tuesday, May 24, 2011

Telomerase Theory of Biological Aging

In one of the previous posts we reviewed the cornerstone Genetic Theory of Aging - Planned Obsolescence Theory, focused upon the encoded programming within our DNA. But recent scientific development gave a road to other approaches linking human genetics with biological aging.

One of the most recent theories based on the gene damage has been the Telomerase Theory of Aging. This theory was born from the surge of technological breakthroughs in genetics and genetic engineering. First discovered by a group of scientists at the Geron Corporation in Menlo Park, California, telomeres are sequences of nucleic acids extending from the ends of chromosomes.

Telomeres

Telomeres are sequences at the ends of chromosomes. Though they are written in the 'alphabet' of the genes, telomeres do not contain the codes for proteins. So telomeres are not themselves genes, but neither are they meaningless junk. Instead these repetitive sequences protect the ends of the chromosome from damage, and prevent the chromosomes from fusing into rings, or binding haphazardly to other DNA in the cell nucleus.

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When a cell divides, the chromosomes are copied by enzyme molecules. These molecules faithfully transcribe the genetic information on each chromosome, producing mirror images of both of the two original strands (which themselves were mirror images of each other). But the enzyme molecules that do the duplicating are unable to completely reproduce the tips of the chromosomes, much as a tape recorder cannot play the last few centimeters of tape in a cassette. As a result, the duplicate chromosome is necessarily slightly shorter than the original, lacking a small amount of the original telomere sequence. The missing DNA does not measurably affect cellular functioning until enough cell divisions have occurred that the telomeres on at least one of the chromosomes in the cell become critically short.

Cells with critically short telomeres alter their character by transcribing a partly distinct set of genes. They also become unresponsive to triggers that would normally stimulate them to divide. Though these growth arrested cells can live on in the body for years, once they have reached this state, they do not under normal circumstances, replicate themselves. They are said to have reached their Hayflick limit (named for the discoverer of the arrested state). Most cells can replicate about 50 times before the telomeres are too short.

Telomerase

Because sperm and egg cells are themselves descended from progenitor cells, if there were no mechanism for replacing lost telomere, then all organisms with linier chromosomes (eukaryotes) would be condemned to quick extinction due to Hayflick limits in their reproductive tissues. Clearly, that's not the case. Instead, there are a number of mechanisms in nature that counteract the natural tendency of telomeres to erode over time.

Scientists discovered that the key element in rebuilding our disappearing telomeres is the "immortalizing" enzyme telomerase, an enzyme found only in germ cells and cancer cells. Telomerase appears to repair and replace telomeres manipulating the "clocking" mechanism that controls the life span of dividing cells. Future development of telomerase inhibitor may be able to stop cancer cells from dividing and presumably may convert them back into normal cells.

This hybrid molecule, part protein, part RNA, is capable of slowing telomere erosion, halting erosion altogether, or lengthening telomeres beyond those in the parent cell. The genes that produce telomerase are found in every potentially replicating cell in the body, including cells at their Hayflick limits, but the genes that produce telomerase are inactive in the great majority of our cells, for the vast bulk of our lives. Those genes are active across the body only in early fetal development. After that point, telomerase is only found in a few special tissues such as antibody producing immune cells, cells that replenish the gut lining, and sperm producing cells.

Further recent research by Don Kleinsek Ph.D., of GeriGene Inc. (one of the few genealogists looking for the genes involved with aging), indicates that telomeres can be repaired by the introduction of the relevant hormone. In other words telomeres and their subsequent processes affect each other. It may be possible, (once we know what each telomere is responsible for), to precisely introduce the necessary hormone and aid genetic repair, as well as the hormonal balance etc.

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Evidence in support of the telomerase hypothesis of aging

  • Telomerase are shorter in most tissues from older individuals compared to younger individuals.
  • Children born with progeria (early aging syndrome) have shortened Telomerase compared to age-matched controls.
  • Telomerase in normal cells from young individuals progressively shorten when grown in cell culture.
  • Experimental elongation of Telomerase extends proliferative capacity of cultured cells.

The role of telomerase in checking aging remained unaddressed, in part because of the cancer-promoting activity of telomerase. In order to circumvent this problem, scientists have successfully tested telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice and have shown that it could restrain cancer. The test revealed that TERT could improve the fitness of epithelial barriers, particularly the skin and the intestine. It also produced a systemic delay in aging accompanied by extension of the median life span.

Does Telomeres Get Shorter to Everyone?

No — and that’s a big surprise. Researchers in Sweden found out that some people’s telomeres do not necessarily get shorter over time. In fact, they found that some people’s telomeres even get longer. This variation at the individual level was hidden by prior studies that averaged results over large population.

What Does Non-Shortening Telomeres Mean?

In the study, 959 individuals donated blood twice, 9 to 11 years apart. On average, the second samples had shorter telomeres than the first. However, around 33% of the people had either a stable or increasing telomere length over a period of around 10 years. What does this mean? Nobody knows. It could be that those people have an amazing cellular anti-aging mechanism or it could be that they have an early sign of cancer (researchers tried to rule this out) or it could be fairly meaningless. What we do know for sure is that aging is a lot more complicated than simply looking at the shortening of telomeres.

Life Affects Telomeres

There is a full literature on telomere that has lately been published. It seemingly is the reason why diseases become more severe at late-life. As our life goes on, cell senescence, illnesses and disease tend to set a limit to longevity. According to research going beyond 120 years is almost impossible if a methods to maintain telomeres lengths are not found.

It is even possible to verify the length of telomeres. Length of telomere can give an approximate of the biological life span of cells and organisms. It has been found that people who experience oxidative stress and suffer from various diseases have much shorter telomere than controlled groups.

Moreover, recent research shows that children, who have had an emotionally traumatic childhood, being sexually abused or beaten, tend to have shorter telomeres, according to a research by Journal Biological Psychiatry.

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Shortening of Telomeres does also offer reliable justification as to why the immune system becomes less responsive to illnesses and infections. The decline in immune functions is caused by the peak of replication of cells. The immune system is unable to reproduce new cells to tackle diseases and infections. For instance, therapies that would increase the telomerase in the human immune cells such as CD4 and CD8 would retard the senescence of cells. The potential benefits would be elevated cell strength to handle stress, deal with diseases such as AIDS and prevent bone loss as well as inducement of inflammatory cytokines.

Telomere theory of aging has direct relations to outcomes such as high blood pressure, psychosocial stress, obesity and a weak lipid statue. This connects the theory to oxidative damage, susceptibility to cardiovascular disease and other theories.

How to Help your Telomeres?

1. Lifestyle




The aim is to maintain appropriate long telomeres. This can be achieved by avoiding all types of stress: physical, environmental and psychological.  Lifestyle guides such as proper diets with a proper daily-recommended volume of vitamins and antioxidants are advised. Friendly relationship promoting positive atmosphere and mental attitudes are necessary.

Medical treatments such as chemotherapy and radiation therapy as well as negative life experiences do also shorten the telomere. Some years of your life might be ripped-off through personal crisis as well as the medical treatment mentioned due to their negative effect on cell division and telomere shortening. Lifestyle is, hence, a prerequisite for longevity to be acquired.

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2. Food and Medical Supplements

It has been found by a ‘recent study conducted on 586 women’ that daily consumers of multi-vitamins have comparatively longer telomere of leukocyte DNA. The telomere is 5.1 percent longer than average people not taking multi-vitamins. This concludes that antioxidant plays an important role in assuring integrity in cell division through maintaining the telomere length.

Telomere shortening can be caused by oxidative damage as it forces an increase rate of duplication of new cells. Therefore, antioxidants can be effective in tackling both diseases and telomere shortening. For instance, l-carnosine can prove to alter or even avoid the telomere damage, in the culture of human diploid fibroblast. Early studies carried out in 1994, depicts that Carnosine does both retard senescence and encourage the generation of juvenile phenotype in culture of human fibroblasts. This elevates the ‘Hayflick limit’ and makes cell reproduction further possible.

Geron have the patent for TA-65 and TA used to activate telomerase. They claim that a vital substance from astragaloside IV acts as an activator of telomerase and by virtue this substance comes from the astragalus root. It is thought that the substance is cycloastragenol, according to the patent, as the substance has not been mentioned. Astragalus pills have many benefits to our biological system such as improving our immune system. Yet Chinese ginger roots are also being claimed to activate telomerase and hence part of the firewall.

RevGenetics’ Astral Fruit is a supplement that contains astragaloside IV. There is 33 mg in every capsule of it and two per day can be consumed. Astragaloside IV is actually being scrutinized for its anti-fibrotic, anti-inflammatory cardioprotective and vasodiliation properties. Eventually, its neuro-protective features acts as a defense against ischemia. Yet, there are not any known side effects of the substance but it has not been in the market for long. Little publications have been made about its impact on inducing telomerase.

Cycloastragenol according Geron, 5 mg of cycloastragenol results in equal activation in telomerase as 100 mg of astragaloside IV. However, apart from patent information cycloastragenol there are no published sources about the substance available. Geron patent recommends that at around 50 to 100 mg of astragaloside IV is consumed. However, two capsules of 33 mg are adequate as potential hazard effects are still not yet known.

Other more versatile firewalls are Green Tea, Allicin, curcumin and resveratrol which tend to restrain the inducement of telomerase for cancer cells. These substances have strong anti-cancer benefits as well as other benefits.


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