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Telomeres and longevity: the long and short of it

Telomeres are located at the tips of chromosomes. Chromosomes contain vital DNA.
Telomeres are located at the tips of chromosomes. Chromosomes contain vital DNA.
Photo credit: http://commons.wikimedia.org/wiki/File:Telomere.JPG

The battle against death begins the moment we are born. The events that occur in our cells throughout our lives influence our health and how long we will live. Living to 50 or 60 years old prior to the 20th century meant living to an old age. Today, it means living beyond 90 years old. The life expectancy of human beings is presently about 78 years old in the United States (averages vary between 40-80 years old depending on the country of inhabitancy) and has steadily increased over the course of time. Due to advances in molecular medicine and dietary improvements, it is thought that life expectancy will increase to 120-150 years old in the not so distant future.

Telomeres [1][2][3]

The search for the fountain of youth has led scientists inside the cell to analyze the effects of daily living (stress, diet and exercise) on its genetic structure and, consequently, life spans of human beings. Scientists are looking at the DNA molecule, and more specifically, at the tips of the DNA molecule, which are composed of telomeres. Through this research, we are now able to understand the cause of aging.

In 1978, Elizabeth Blackburn and Joseph Gall of Yale University published their work on telomeres. During the course of her postdoctoral studies at Yale, Blackburn identified the structure of telomeres as simple repeated DNA sequences comprising the ends of chromosomes that function to protect the end of the chromosome from deterioration during the replication process. Telomeres are like aglets, or tips, at the ends of shoelaces. Just as the shoelace tips prevent fraying of the laces from repeated tying, telomeres hold the vital DNA code intact, preventing it from fraying as the molecule experiences repeated replications over the course of time.

As cells age, they are subject to attack by free radicals in the body and environment. But our cells have the ability to regenerate and duplicate themselves before being completely destroyed. Each time a cell divides, the DNA molecule splits and rebuilds itself making two new DNA molecules. The DNA is duplicated but the replication process does not continue to the ends of the chromosome. At its ends are telomeres, which are regions of repetitive DNA and a chain of repeating enzymes that protect the end of the chromosome from deterioration. Telomeres block the ends of the chromosome during cell division by acting as a buffer against asynchronous errors, which are inevitable occurrences during the replication process. The errors result in the loss of a small portion of the DNA molecule. Typically, these errors occur more frequently on telomeres where there is no important DNA information so mistakes confined to this region are not significant. If cells divided without telomeres, vital DNA sequences and the ends of chromosomes would be lost along with the necessary information they contain. So, during DNA replication, the telomeres align the DNA while protecting it from being copied out of the normal pattern and they protect a cell's chromosomes from forming abnormalities such as fusing with each other, rearranging, or becoming cancerous. The telomeres are also consumed in the replication process but they are replenished by an enzyme called telomerase reverse transcriptase. If they were not replenished, the cell would die.

Scientists now know that the length of telomere chains shorten as we grow older. Eventually, the telomeres shorten to the point where the losses that occur in replication begin to affect the DNA molecule sequence and, consequently, prevent the cell’s ability to duplicate itself. Without the vital DNA code, the cell cannot reproduce and this is why we age. As telomeres shorten, this restricts the number of divisions that a cell can undergo and aging occurs at the cellular level setting limits on health and life spans. Cells evading this programmed destruction become immortal and result in cancers.

Telomeres

http://www.youtube.com/watch?v=CCNuG2ejBuE

Telomerase [1][2][3]

In 2009, Elizabeth Blackburn, Carol Greider, and Jack Szostak were awarded the Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. Telomerase turns telomere production on the DNA molecule on and off. As we age, the concentration of telomerase in our cells decreases. Turning them on would increase our life span and turning them off would limit the spread of immortal cancer cells.

Telomerase has the ability to repair and lengthen telomeres in human cells. Human telomeres shorten at a faster rate than many lower organisms, which results in mortality. As telomeres shorten, signals are sent to cells to arrest their growth (senescence). Human telomeres are approximately 10,000 base pairs long at birth. At around 100 years of age, that amount decreases to about 5,000 base pairs. Telomerase can reverse or stop the shortening process. It typically increases the length of telomeres during the formation of gametes (sperm and eggs) for the purpose of ensuring that offspring inherit long young telomeres.

The Future: Longer life spans? [1][4]

Research has shown that people who live long lives tend to have long telomeres. Studies have also shown that long term exercise activates telomerase and prevents shortening of telomeres. Other studies done on animal models in the laboratory have shown that populations of animals forced to breed early have unusually long telomeres compared to populations of animals in the wild. A person born to a young mother lives longer than a child born to an older mother. The reason for this has to do with inheritance of long telomeres. A female’s eggs are produced while in the mother’s womb. After birth, when the female reaches puberty, the long telomere egg cells are released from the ovaries before the short telomere egg cells so they are the first to be fertilized and develop into an embryo. A child born to a woman later in life is more likely to inherit short telomeres, which results in a shorter life span. Because of the inheritance of the shorter telomeres, having children later in life also increases the chance for birth defects or miscarriages.

Longer life spans may also mean longer health spans. Many health problems associated with the aging process include cardiovascular and neurodegenerative diseases, arthritis, osteoporosis, and cancers. Researching genes that encode for telomerase will enable us to address health issues associated with aging. Using telomerase technology, we can delay or even avoid age-related health problems altogether as the life span is lengthened.

"Anti-aging medicine is not about stretching out the last years of life. It's about stretching out the middle years of life... and actually compressing those last few years of life so that diseases of aging happen very, very late in the life cycle, just before death, or don't happen at all." -- Dr. Ronald Klatz of the American Academy of Anti-Aging

Women@Google: Dr. Elizabeth Blackburn

http://www.youtube.com/watch?v=irUQEG4BSK4

Can we slow down aging or even stop the process altogether? We may have it in our technological power to make immortality a reality. Perhaps someday we can forego the anti-aging clinics and therapies that promise us a longer life if we pay hundreds and thousands of dollars for treatments. Hormone therapy and anti-aging cosmetic surgery offer no guarantees of an extended health or life span – but telomerase does. A longer and healthier life span may be more under our control than we think. Stress plays a role in affecting the life of a cell and thus shortening of telomeres. For humans to extend life, we must work on lowering stress levels, eliminate toxins in our diet and environment, and find a method for increasing and preserving the length of our cells' telomeres. The 21st century may in fact be the time in which we identify the secrets of eternal life.

“And in which we say that life is eternal but continue to struggle to survive.
-- Neale Donald Walsch

Reference links:

  1. http://www.viewzone.com/aging.html
  2. http://en.wikipedia.org/wiki/Telomere
  3. http://www.sciencedaily.com/releases/2009/11/091111200225.htm
  4. http://www.sciencedaily.com/releases/2009/11/091130161806.htm

Copyright ©2012 Joyce E.M. Wall

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