Telomeres and Telomerase

Facts About Telomeres and Telomerase

To better understand telomeres and telomerase, let's first review some basic principles of biology and genetics. The human body is an organism formed by adding many organ systems together. Those organ systems are made of individual organs. Each organ contains tissues designed for specific functions, Skin - Bones - Blood - Hair .etc . Tissues are made of cells that have joined together to perform those special functions. Each cell is then made of smaller components called organelles, including the nucleus , mitochondria , endoplasmic reticulum , Golgi apparatus , vesicles , and vacuoles.

The nucleus contains structures called chromosomes that are actually "packages" of all the genetic information that is passed from parents to their children. In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between Y males and X females. The genetic information, or "genes," is really just a series of bases called Adenine (A), Guanine (G), Cytosine (C), and Thymine (T). Adenine always bonds with Thymine and Guanine to Cytocine, The double helix base pairs can represent four data positions and make up our cellular alphabet that create the sequences, or instructions needed to form our bodies. In order to grow and age, our bodies must duplicate their cells. This process is called mitosis. Mitosis is a process that allows one "parent" cell to divide into two new "daughter" cells. inside the nuleus during mitosis, cells make copies of their genetic material, the DNA unzips into two parts (cytokinesis), during this split, mitotic spindle fibers pull the chromatids apart toward opposite poles, and each new half is re-built to become two identical copies of DNA. immediately after cytokinesis, the cell membrane pinches in at the cell equator using a contractile ring, as it closes a cleft called the cleavage furrow is made. the furrow forms an intercellular bridge, the bridge is then broken and resealed to form two identical daughter cells

Your genome consists of more than 3 billion base pairs of DNA, which is a lot to squeeze into the nucleus of a cell, but the cell accomplishes this by winding up the DNA and compressing it like a slinky into chromosomes. Our genome contains around 20,000 genes and vary in size from a few hundred DNA bases to more than 2 million bases. Most cells in the human body contain 22 pairs of chromosomes plus a pair of sex chromosomes.

What are Telomeres ?

Telomere (tel-uh-meer) from the Greek telos (end) and meros (part) - Telomeres are sections of DNA found at the ends of each of our chromosomes that shorten with each cell division and act like a burning fuse, they consist of the same sequence of bases repeated over and over. In humans the telomere sequence is TTAGGG, and this sequence ranges from 8,000 base pairs in newborns to 3,000 base pairs in adults and as low as 1,500 in elderly people. Dr Bill Andrews says, We are concieved with 15,000 Telomeres, born with 10,000 and die at 5,000. Telomere activity is controlled by two mechanisms: erosion and addition. Erosion, occurs each time a cell divides. Addition is determined by the activity of telomerase.

What do Telemeres do ?

1) They help to organise each of our 46 chromosomes in the nucleus? (control centre) of our cells?.

2) They protect the ends of our chromosomes by forming a cap, much like the plastic tip aglets on shoelaces. If the telomeres were not there, our chromosomes may end up sticking to other chromosomes.

3) They allow the chromosome to be replicated properly without error during cell division.

Every time a cell carries out DNA replication (Mitosis) the chromosomes are shortened, without telomeres, 25-200 bases would be lost, however, because the ends are protected by telomeres, the only part of the chromosome that is lost, is the telomere, and the DNA is left undamaged. Without telomeres, important DNA would be lost every time a cell divides (usually about 50 to 70 times throughout a lifetime).

What happens to telomeres as we age ?

Two main factors contribute to telomere shortening during cell division.

"The end replication problem" during DNA replication: This accounts for the loss of about 50 base pairs per cell division..

"Oxidative stress": Accounts for the loss of another 50-100 base pairs per cell division. The amount of oxidative stress in the body is thought to be affected by lifestyle factors such as diet, smoking and stress.

When the telomere becomes too short, the chromosome reaches a 'critical length' and can no longer be replicated, This 'critical length' triggers the cell to die by a process called apoptosis, also known as programmed cell death.

What is Telomerase ?

Telomerase is an enzyme that adds nucleotide TTAGGG telomere sequences to the ends of chromosomes. Telomerase is only found in very low concentrations in our somatic cells. Because these cells do not regularly use telomerase they age leading to a reduction in normal function, so the result of ageing cells, is an ageing body. Telomerase is found in high levels in germline? cells (egg and sperm) and stem cells, in these cells telomere length is maintained after DNA replication and the cells do not show signs of ageing. Telomerase is also found in high levels in cancer? cells. This enables cancer cells to be immortal and continue replicating themselves. If telomerase activity was switched off in cancer cells, their telomeres would shorten until they reached a 'critical length'. This would, prevent the cancer cells from dividing uncontrollably to form tumours.

So Telomerase is only expressed in embryo cells, adult stem cells and sex cells "Sperm and Egg", this is why our children are born younger than we are even though they come from our old cells. The Telomerase gene is in every living Somatic "Body" cell, but it is turned off.

Telomeres and Aging?

Mice models lacking the enzyme telomerase were found to show signs of premature ageing..However, it is not certain whether telomere shortening is responsible for ageing in humans or whether it is just a sign of ageing, like grey hair. There are several indications that telomere length is a good predictor of lifespan, newborn babies tend to have telomeres ranging in length from around 8,000 to 13,000 base pairs. It has been observed that this number tends to decline by around 20-40 base pairs each year. So, by the time someone is 40 years old they could have lost up to 1,600 base pairs from their telomeres.

The Hayflick Limit

Leonard Hayflick, professor of anatomy at the University of California at San Francisco, advanced the concept 50 years ago. The Hayflick Limit is a concept that helps to explain the mechanisms behind cellular aging. The concept states that a normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore, and will break down by programmed cell death or apoptosis. The Hayflick Limit, he contended, was both an explanation for the phenomenon of ageing and a demolition of the wishful view (of some) that the human lifespan need have no upper limit. But although he correctly identified the cell nucleus as the location of the responsible mechanism, it fell to others to discern the structures involved. It was 2009 Nobel Prize winning biologists Elizabeth Blackburn and Carol Greider who showed how the cell keeps a tally of the number of times it has divided during its progress towards the Hayflick Limit.

Telomeres had been discovered at UC Berkeley by Elizabeth Blackburn in the 1970s. Then, in 1985 she and then graduate-student Carol Greider discovered the enzyme telomerase. Greider and her supervisor Blackburn started to investigate if the formation of telomere DNA could be due to an unknown enzyme. On Christmas Day, 1984, Greider discovered signs of enzymatic activity in a cell extract. Greider and Blackburn named the enzyme telomerase, purified it, and showed that it consists of RNA as well as protein

The Discovery of Telomeres

In the early phase of her research career, Elizabeth Blackburn mapped DNA sequences. When studying the chromosomes of Tetrahymena, a unicellular ciliate organism, she identified a DNA sequence that was repeated several times at the ends of the chromosomes. The function of this sequence, CCCCAA, was unclear. At the same time, Jack Szostak had made the observation that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells.

Blackburn presented her results at a conference in 1980. They caught the interest of Jack Szostak and he and Blackburn decided to perform an experiment that would cross the boundaries between very distant species, From the DNA of Tetrahymena, Blackburn isolated the CCCCAA sequence. Szostak coupled it to the minichromosomes and put them back into yeast cells. The results, which were published in 1982, were striking, the telomere DNA sequence protected the minichromosomes from degradation. As telomere DNA from one organism, Tetrahymena, protected chromosomes in an entirely different one, yeast, this demonstrated the existence of a previously unrecognized fundamental mechanism. Later on, it became evident that telomere DNA with its characteristic sequence is present in most plants and animals, from amoeba to man.

Using Tetrahymena, a fresh-water single-celled organism with a large number of telomeres, Greider set out to look for a hypothetical enzyme that relengthened shortened telomeres. She made extracts from Tetrahymena cells and examined whether artificial telomeres could be elongated by enzymes present in the extracts. After about nine months of trying variations on these experiments, she identified the first signs of her enzyme on Christmas Day, 1984. They named it “telomerase” and published their findings in the scientific journal Cell.

Identification of a Specific Telomere Terminal Transferase Activity in Tetrahymena Extracts

Elizabeth H. Blackburn has US and Australian citizenship. She was born in 1948 in Hobart, Tasmania, Australia. After undergraduate studies at the University of Melbourne, she received her PhD in 1975 from the University of Cambridge, England, and was a postdoctoral researcher at Yale University, New Haven, USA. She was on the faculty at the University of California, Berkeley, and since 1990 has been professor of biology and physiology at the University of California, San Francisco.

Carol W. Greider is a US citizen and was born in 1961 in San Diego, California, USA. She studied at the University of California in Santa Barbara and in Berkeley, where she obtained her PhD in 1987 with Blackburn as her supervisor. After postdoctoral research at Cold Spring Harbor Laboratory, she was appointed professor in the department of molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore in 1997.

Jack W. Szostak is a US citizen. He was born in 1952 in London, UK and grew up in Canada. He studied at McGill University in Montreal and at Cornell University in Ithaca, New York, where he received his PhD in 1977. He has been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General Hospital in Boston. He is also affiliated with the Howard Hughes Medical Institute..

New Discoveries - UNDER CONSTRUCTION

Researchers at the University of California Berkeley have captured the most detailed images to date of telomerase, the enzyme that lengthens the ends of chromosomes and plays a critical role in aging. These images provide long-sought after insight into how telomerase works, and will help guide the design of drugs that target the enzyme, which could have some interesting implications for cancer and aging.

Weird DNA

Methuselah is a 4,845-year-old bristlecone pine tree in eastern California, named after the Biblical figure with the longest lifespan in the Bible of 969 years. Methuselah's exact location is undisclosed to protect it from vandalism. Methuselah was the world's oldest known living non-clonal organism, until the 2013 discovery of another pine germinated in 3051 BC with an age over 5,000 years. This is the first time that we have identified the detailed structure of the telomerase component from plants, so in terms of fundamental research, this is a really big breakthrough because now finally we have a way to study telomerase in plants and to understand how different or similar they are from animals, Could the discovery possibly lead to humans one day living as long as the fabled "Methuselah" tree, a bristlecone pine species that can live over 5,000 years? Maybe one day.

10 DNA Facts

1. Around 5-8% of your DNA isn't human - it's viral DNA. Scientists believe we carry about 100,000 pieces of DNA from retroviruses that have accumulated over the course of human evolution.

2. We share 96% of our DNA with primates such as chimpanzees, gorillas and orangutans. - But we are also genetically related to bananas - with whom we share 50% of our DNA - and slugs - with whom we share 70% of our DNA.

3. Around 99.9% of the DNA in all humans is identical. - It is the tiny 0.1% difference that allows us to be individuals with different skin, hair and eye colour. Scientists also believe that the remaining 0.1% holds important clues about the causes of diseases.

4. Humans have approximately 10 trillion cells. - If we unravelled our entire DNA, it would stretch six billion miles - which would be the same as travelling from the Earth to the sun 65 times.

5. Although rare, it is possible for a person to have two completely different DNA profiles. - a phenomenon known as chimera. It can happen during a normal pregnancy - where the mother retains some of her baby's DNA - or when a foetus absorbs its twin. A person can also be a chimera if they undergo a bone marrow transplant where the donor's bone marrow continues making blood cells that have the donor's DNA.

6. Almost all the cells in our body have DNA - the exception being red blood cells. However, all red blood cells start with DNA - they simply destroy their nucleus once it is no longer needed as part of the maturation process.

7. Human beings have 20,000 to 25,000 genes but they account for only about 3% of our DNA. - Scientists are not sure about the function of the remaining 97%, although they think it may have something to do with controlling the genes.

8. The human genome contains three billion base pairs of DNA. - It is estimated that if you type eight hours a day at 60 words per minute, it would take approximately 50 years to type the human genome.

9. Unlike the octopus, we can't naturally edit our own genes. - But scientists have developed a complex protein-based tool called CRISPR-Cas9 which has been used to successfully alter DNA in defective embryos to prevent inherited diseases.

10. We all know about the double helix structure, but scientists have recently discovered another form of DNA in living human cells. - It's called i-motif and has been described as "a four-stranded knot of DNA".