"Hayflick LimitThe 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 timesbefore it cannot divide anymore, and will break down by programmed cell death or apoptosis.The concept of the Hayflick Limit revised Alexis Carrel's earlier theory, which stated thatcells can replicate themselves infinitely. Leonard Hayflick developed the concept while at theWistar Institute in Philadelphia. The concept of the Hayflick Limit helped scientists study theeffects of cellular aging on human populations from embryonic development to death,including the discovery of the effects of shortening repetitive sequences of DNA, calledtelomeres, on the ends of chromosomes. Elizabeth Blackburn, Jack Szostak and CarolGreider received the Nobel Prize in Physiology or Medicine in 2009 for their work on geneticstructures related to the Hayflick Limit.Hayflick limit for some cells are given following.I) Fibroblast - 50 Cell divisionII) Older adult - 10-20 cell divisionIII) Mouce cells - 10-15 divisionsIV) Tortoise- 100 divisionsHayflick limit and ageing The Hayflick limit has been found to correlate with the length of the telomere region at theend of a strand of DNA. During the process of DNA replication, small segments of DNA ateach end of the DNA strand (telomeres) are unable to be copied and are lost after each timeDNA is duplicated. About 2000 repeats of telomere sequence (TAAGGG) is present in telomere region.Each division resulting in loss of 100 bp (about 16 TAAGGG sequence).After 125 micotic division the telomere completely lost. The telomere region of DNA doesnot code for any protein; it is simply a repeated code on the end region of DNA that is lost.After many divisions, the telomeres become depleted and the cell begins apoptosis. This is amechanism that prevents replication error that would cause mutations in DNA. Once thetelomeres are depleted, due to the cell dividing many times, it will no longer divide. This iswhen the cell has reached its Hayflick limit. This process does not take place in most cancer cells due to an enzyme called telomerase.This enzyme maintains telomere length, which results in the telomeres of cancer cells nevershortening. This gives these cells infinite replicative potential. A proposed treatment forcancer is the usage of telomerase inhibitors that would prevent the restoration of the telomere,allowing the cell to die like other body cells On the other hand, telomerase activators mightrepair or extend the telomeres of healthy cells, thus extending their Hayflick limit.Telomerase activation might also lengthen the telomeres of immune system cells enough toprevent cancerous cells from developing from cells with very short telomeres.ProgeriaProgeria is genetic disorder generally associated with early shortness of telomeres. Progeria istwo types.A) Hutchinson-Gilford progeria syndrome (HGPS)It is a rare genetic condition that causes a child's body to age fast. Most kids with progeria donot live past the age of 13. The disease affects both sexes and all races equally. It affectsabout 1 in every 4 million births worldwide.A single mistake in a certain gene causes it tomake an abnormal protein. When cells use this protein, called progerin, they break down more easily. Progerin builds up in many cells of kids with progeria, causing them to grow oldquickly.Progeria is not inherited, or passed down in families.Causes Steps in normal cell Steps in cell with progeriaThe gene LMNA encodes a protein called prelamin A.Prelamin A has a farnesyl group attached to its end.Farnesyl group is removed from prelaminFarnesyl group remains attached to prelamin A.A.Abnormal form of prelamin A isNormal form is called lamin A.called progerin.Lamin A is not anchored to the nuclear rim. Progerin is anchored to the nuclear rim.Normal state of the nucleus. Abnormally shaped nucleusSymptomsMost kids with progeria look healthy when they're born, but they start to show signs of thedisease during their first year. Babies with progeria do not grow or gain weightnormally.They develop physical traits including:? A bigger head? Large eyes? A small lower jaw? A thin nose with a "beaked" tip ? Ears that stick out? Veins you can see? Slow and abnormal tooth growth? A high-pitched voice? Loss of body fat and muscle? Hair loss, including eyelashes and eyebrowsAs children with progeria get older, they get diseases you'd expect to see in people age 50and older, including bone loss, hardening of the arteries, and heart disease. Children withprogeria usually die of heart attacks or strokes.Progeria doesn't affect a child's intelligenceor brain development at all. A child with the condition isn't any more likely to get infectionsthan other kids, either.B) Werner syndromeWerner syndrome (WS), also known as "adult progeria",is a rare, autosomalrecessiveprogeroid syndrome (PS), which is characterized by the appearance ofpremature aging.Werner syndrome is characterized by the dramatic, rapid appearance of features associatedwith normal aging. Individuals with this disorder typically grow and develop normally untilthey reach puberty. Affected teenagers usually do not have a growth spurt, resulting in shortstature. The characteristic aged appearance of individuals with Werner syndrome typicallybegins to develop when they are in their twenties and includes graying and loss of hair; ahoarse voice; and thin, hardened skin. They may also have a facial appearance described as"bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunkdue to abnormal fat deposition.As Werner syndrome progresses, affected individuals maydevelop disorders of aging early in life, such as cloudy lenses (cataracts) in both eyes, skinulcers, type 2 diabetes, diminished fertility, severe hardening of the arteries (atherosclerosis), thinning of the bones (osteoporosis), and some types of cancer. It is not uncommon foraffected individuals to develop multiple, rare cancers during their lifetime. People withWerner syndrome usually live into their late forties or early fifties. The most common causesof death are cancer and atherosclerosis.How common is Werner syndrome?Werner syndrome is estimated to affect 1 in 200,000 individuals in the United States. Thissyndrome occurs more often in Japan, affecting 1 in 20,000 to 1 in 40,000 people.What genes are related to Werner syndrome?Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions forproducing the Werner protein, which is thought to perform several tasks related to themaintenance and repair of DNA. This protein also assists in the process of copying(replicating) DNA in preparation for cell division. Mutations in the WRN gene often lead tothe production of an abnormally short, non-functional Werner protein. Research suggests thatthis shortened protein is not transported to the cell's nucleus, where it normally interacts withDNA. Evidence also suggests that the altered protein is broken down more quickly in the cellthan the normal Werner protein. Researchers do not fully understand how WRN mutationscause the signs and symptoms of Werner syndrome. Cells with an altered Werner proteinmay divide more slowly or stop dividing earlier than normal, causing growth problems. Also,the altered protein may allow DNA damage to accumulate, which could impair normal cellactivities and cause the health problems associated with this condition.How do people inherit Werner syndrome?Werner syndrome is inherited in an autosomal recessive pattern, which means both copies ofthe WRNgene in each cell have mutations. The parents of an individual with Wernersyndrome each carry one copy of the mutated gene, but they typically do not show signs andsymptoms of the condition. "