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Progeria
Classification & external resources

ICD-10	E34.8
ICD-9	259.8
OMIM	176670
DiseasesDB	32102
MedlinePlus	001657
eMedicine	derm/731
MeSH	D011371

Progeria narrowly refers to Hutchinson-Gilford Progeria syndrome, but the term is also used more generally to describe any of the so-called "accelerated aging diseases". The word progeria is derived from the Greek for "prematurely old". Because the "accelerated aging" diseases display different aspects of aging, but never every aspect, they are often called "segmental progerias" by biogerontologists.

Hutchinson-Gilford Progeria syndrome is an extremely rare genetic condition which causes physical changes that resemble greatly accelerated aging in sufferers. The disease affects between 1 in 4 million (estimated actual) and 1 in 8 million (reported) newborns. Currently, there are approximately 40-45 known cases in the world. There is no known cure. Most people with progeria die around 13 years of age.^[1] Progeria is of interest to scientists because the disease may reveal clues about the process of aging. Unlike most other "accelerated aging diseases" (such as Werner's syndrome, Cockayne's syndrome or xeroderma pigmentosum), progeria is not caused by defective DNA repair.

The condition was first identified in 1886 by Jonathan Hutchinson and Hastings Gilford. The condition was later named Hutchinson-Gilford Progeria syndrome (HGPS). Around 100 cases have been identified since then.^[1]

A 2006 report in Nature said progeria may be a de novo dominant trait. It develops during cell division in a newly conceived child or in the gametes of one of the parents. It is caused by mutations in a LMNA (Lamin A protein) gene on chromosome 1.

Nuclear lamina is a protein scaffold around the edge of the nucleus that helps organize nuclear processes such as RNA and DNA synthesis.

Prelamin A contains a CAAX box at the C-terminus of the protein (where C is a cysteine and A is any aliphatic amino base. This ensures that the cysteine is farnesylated, and this allows Prelamin A to bind membranes, specifically the nuclear membrane. After Prelamin A has been localized to the cell nuclear membrane the C-terminal amino acids, including the farnesylated cysteine, are cleaved off by a specific protease. The resulting protein is now Lamin A, is no longer membrane-bound and carries out functions inside the nucleus. In HGPS the recognition site that the enzyme requires for the cleavage of Prelamin A to Lamin A is mutated. Lamin A cannot be produced and Prelamin A builds up on the nuclear membrane, causing a characteristic nuclear blebbing.^[2] This results in the premature aging symptoms of progeria, although the mechanism connecting the misshapen nucleus to the symptoms is not known. A mouse model of progeria exists, though in the mouse the LMNA prelamin A is not mutated, but instead the specific protease that is required to remove the C-terminus of Prelamin A is missing. Both cases result in the build up of farnesylated Prelamin A on the nuclear membrane and in the characteristic nuclear LMNA blebbing. Fong et al use a farnesyl transferase inhibitor (FTI) in this mouse model to inhibit protein farnesylation of Prelamin A. Treated mice had greater grip strength, lower likelihood of rib fracture and may live longer than untreated mice.^[3] Note that this method does not directly 'cure' the underlying cause of progeria. This method prevents Prelamin A going to the nucleus in the first place so no Prelamin A can build up on the nuclear membrane, but equally there is no production of normal Lamin A in the nucleus. Luckily Lamin A does not appear to be essential, indeed mouse models in which the genes for Prelamin A and C are knocked out show no symptoms. This also shows that it is the build up of Prelamin A in the wrong place, rather than the loss of the normal function of Lamin A that causes the disease.

A study which compared HGPS patient cells with the skin cells from LMNA young and elderly human subjects found similar defects in the HGPS and elderly cells, including down-regulation of certain nuclear proteins, increased DNA damage and demethylation of histone leading to reduced heterochromatin.^[4] Nematodes over their lifespan show progressive lamin changes comparable to HGPS in all cells but neurons and gametes.^[5] These studies suggest that lamin A defects contribute to normal aging.

Contents 1 Symptoms 2 Influences and references on or in popular culture 3 See also 4 References 5 External links

Symptoms generally begin appearing around 18-24 months of age. The condition is distinguished by limited growth, alopecia and a characteristic appearance with small face and jaw and pinched nose. Later the condition causes wrinkled skin, atherosclerosis and cardiovascular problems. Mental development is not affected. Individuals with the condition rarely live more than 16 years; the longest recorded life-span was 29 years. The development of symptoms is comparable to aging at a rate six to eight times faster than normal, although certain age-related conditions do not occur. Specifically, victims show no neurodegeneration or cancer predisposition. The people diagnosed with this disease usually have fragile elderly-like bodies.

• In the 1986 film, The Aurora Encounter, the alien is portrayed by real-life progeric Mickey Hays, which resulted in a controversy around the film as exploitative of a minor with a disorder, in addition to his mother allowing him to smoke cigars on-set with Jack Elam.
• In the 1988 the Anime film Akira, by director Katsuhiro Otomo, the three children with very powerful telekinetic and telepathic gifts, as well as some alluded to precognitive gifts, suffered from what seemed to be a progeria-like disease. - [ False. The backstory to the movie was that the children were experimented on from an early age, causing their physical development. In the making of Akira documentary, it is shown that the children were all supposed to be around age 40. That's why they all knew Akira, who blew up Tokyo in 1988, with the movie being set in the future. ]
• The movie Blade Runner featured a character named Sebastian who suffers from a progeria-like disease which he refers to as "Methuselah Syndrome". The name is ironic, as progeria causes rapid aging and death, while Methuselah was known for living to a very great age.
• In the The X-Files episode "Young at Heart", a doctor created a method of reversing progeria and rejuvenating humans.
• In the science-fiction novel Otherland by Tad Williams, a young boy in his teenage years (Orlando Gardiner) is affected by progeria.
• In 1996, the movie Jack tells the story of a 10 year old boy (Robin Williams) with an aging disorder much like progeria, although depicted closer to an accelerated version of Werner syndrome.
• In the 1983 movie The Hunger, Dr. Sarah Roberts's work on aging, including a study of progeria, attracts the attention of immortal Miriam Blaylock, who fears her mate John will soon start fatal rapid aging.
• In season two, episode two of The Venture Bros., The Monarch insults Dr. Thaddeus Venture's attire (a short-sleeve jumpsuit) by saying their captors will "...think you're a three-year-old with progeria and take pity on us."
• In season four, episode seven (The Scientific Method) of Star Trek: Voyager, the Doctor briefly brings up progeria, stating it was a rare case in children and that it was eradicated centuries ago.
• In the novel Haunted by Chuck Palahniuk, Brandon Whittier, who organizes the retreat, is a progeria sufferer.
• In the 2006 futuristic animated film Renaissance, the character of Claude Muller suffers from progeria. The disease also features as a significant plot point in the movie.
• In the animated series "Sealab 2021", numerous references are made about progeria being "nature's cruelest joke".
• In the book The Sigma Protocol by Robert Ludlum, the children imprisoned in the "Clockworks" have progeria.
• In the Filipino TV show "I-Witness", they documented 2 children with a real case of progeria.
• A charity CD to raise money into the research of progeria was released in 2006. Titled - 'VOICES OF TOMORROW', the song features young UK progeria sufferer Hayley Okines on vocals. There is more information at *Song For Progeria
• In the popular sci-fi series Dark Angel, many of the transgenics suffer from progeria.
• In season 2 of the popular youth sci-fi series "The Tribe" occur cases of a progeria-like disease caused by the virus that killed all adults in the beginning of the first season.
• The protagonist of the 2000 play "Kimberly Akimbo" by David Lindsay-Abaire is a 16 year old girl with progeria.

• Accelerated aging disease
• Biogerontology
• Cockayne syndrome
• DNA repair
• Degenerative disease
• Farnsyltransferase
• Genetic disorder
• Laminopathies
• Senescence
• Werner syndrome
• Xeroderma pigmentosum

1. ^ ^{a b} Steve Sternberg (April 16, 2003). Gene found for rapid aging disease in children. USA Today. Retrieved on 2006-12-13.
2. ^ (March 2, 2006) "Ageing nucleus gets out of shape". Nature 440: 32–34. PMID 16511477. 
3. ^ Loren G. Fong (March 17, 2006). "A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria". Science 311 (5767): 1621-–3. PMID 16484451. 
4. ^ Scaffidi P, Misteli T (May 19, 2006). "Lamin A-dependent nuclear defects in human aging". Science 312 (5776): 1059-–63. PMID 16645051. 
5. ^ Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J (December 27, 2005). "Age-related changes of nuclear architecture in Caenorhabditis elegans". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA) 102 (46): 16690-16695. PMID 16269543. 

• "A Time to Live" – Seattle Post-Intelligencer feature about Seth Cook, a child with Progeria.
• Bodyshock: The 80-Year-Old Children
• The Girl who is older than her Grandmother
• "Family tormented by ageing disease" – BBC News article on a family with Progeria; cites study that progeria is inheritable.
• Hutchinson-Gilford Progeria syndrome Network
• Media – a list of references in common culture
• Progeria Research Foundation
• Progeria News and Media Collection
• Segmental Progeria
• Farnesyl transferase inhibitors may help children with Hutchinson-Gilford progeria – Article on the use of FTI inhibitors as potential treatment