Progeria : halk dilindeki adıyla erken yaşlanma hastalığı !
konu hakkında yapılan bilimsel araştırmalar
hastalığın çağresini bulmaktan ziyade hastalığa sebep olan faktörleri bulmak ve bu sayede
insanlığın ömürünü uzatabilmek
Name = Progeria |
Image = |
Caption = |
DiseasesDB = 10704 |
ICD10 = ICD10|E|34|8|e|20 |
ICD9 = ICD9|259.8 |
ICDO = |
OMIM = 176670 |
MedlinePlus = |
eMedicineSubj = derm |
eMedicineTopic = 731 |
MeshID = D011371 |
The term progeria narrowly refers to Hutchinson-Gilford Progeria syndrome, but the term is issued to describe any of the so-called " accelerated aging disease
s". The word progeria is derived from the Greek for "old age".
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 51 known cases in the world. There is no known cure, but several discoveries have been made that have lead to greater understanding and perhaps eventual treatment.<ref>Capell BC, Collins FS, Nabel EG. mechanism of Cardiovascular Disease in Accelerated Aging Syndromes. Circulation Research 2007 Jul 6; Vol. 101 (1), pp. 13-26.</ref> Most people with progeria die around 13 years of age.<ref name="USA T">cite web | url=http://www.usatoday.com/news/science/2003-04-16-agin-gene_x.htm
| title=Gene found for rapid aging disease in children | author=Steve Sternberg | date=April 16, 2003 | publisher=USA Today | accessdate=2006-12-13 </ref> 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
1886 yılı olayları, ölümler, doğumlar ve diğer önemli gelişmeler Jonathan Hutchinson
...Tümünü okumak için linke tıklayınız.
and Hastings Gilford
. The condition was later named Hutchinson-Gilford Progeria syndrome (HGPS). Around 100 cases have been identified since then.<ref name="USA T"/>
A 2003 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 gamete
s of one of the parents. It is caused by mutation
s in a LMNA ( Lamin A protein
Albüminli madde; organizmanın en önemli yapı taşı. Amino asitlerin birleşmesinden meydana gelmiş karmaşık yapılı organik moleküllerdir. Kelime olarak “en önemli” mânâsına gelen protein, gerçekten de canlının en önemli maddesini teşkil eder. Bütün canlıların hücreleri protein ihtivâ eder. Proteinler hücre stoplazmasında çözünmüş hâlde bulunur. Kas, karaciğer gibi organ ve dokuların % 80-90’ı proteindir. Kemik sistemi ve yağ dokusunda ise protein daha azdır. gene
...Tümünü okumak için linke tıklayınız.
on chromosome 1
is a protein scaffold
around the edge of the nucleus
that helps organize nuclear processes such as RNA
Ribonükleik asit, nükleotidlerin ard arda yerleşmesiyle birleşmiş tek diziden oluşan yüksek kaliteli moleküldür. Hücrelerde DNA ile birlikte çalışarak protein sentezlenmesinde rol alır. Nükleotid dizisinde şeker ribozdur, azotlu bazlar ise adenin, sitozin, guanin ve urasildir. DNA
...Tümünü okumak için linke tıklayınız.
Prelamin A contains a
DNA Alm. Deutscher Normenausschuss, Fr. Acide desoxyribonucleique, İng. Desoxyribonucleic asid. Kalıtımda rol oynayan organik bir molekül. Bir nükleik asit çeşidi. “Deoksiribo nükleik asit” adını alır. Kısaca “DNA” olarak gösterilir. Canlılarda yönetici bir moleküldür. Hücrenin protein ve enzim sentezinde rol oynar. Ayrıca yeni bir hücre meydana getirecek gerekli elemanları taşıdığından hücre bölünmesinin esasını teşkil eder. CAAX box
İlk defa A.F.Mıescwer adl
...Tümünü okumak için linke tıklayınız.
at the C-terminus
of the protein (where C is a cysteine
and A is any aliphatic amino acids
). 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.<ref>cite journal | title=Ageing nucleus gets out of shape|journal= Nature
| year=2006| date=March 2, 2006 | volume=440 | pages= 32–34 |id=PMID 16511477</ref> 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.<ref>cite journal | author=Loren G. Fong| title=A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria | journal= Science
| year=2006 | date=March 17, 2006 | volume=311 | issue=5767 | pages=1621-–3| url=http://www.sciencemag.org/cgi/content/abstract/1124875v1
|id=PMID 16484451</ref> 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
.<ref>cite journal | author=Scaffidi P, Misteli T | title=Lamin A-dependent nuclear defects in human aging | journal= Science
| year=2006 | date=May 19, 2006 | volume=312 | issue=5776 | pages=1059-–63 | id=PMID 16645051</ref> Nematode
s over their lifespan show progressive lamin changes comparable to HGPS in all cells but neuron
s and gamete
s.<ref>cite journal | author=Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J| title=Age-related changes of nuclear architecture in Caenorhabditis elegans | journal= PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA) | year=2005 | date=December 27, 2005 | volume=102 | issue=46|pages=16690-16695| url=http://www.pnas.org/cgi/content/full/102/46/16690
|id=PMID 16269543</ref> These studies suggest that lamin A defects contribute to normal aging
The earliest symptoms include failure to thrive
(FTT) and a localized scleroderma
-like skin condition. As the child ages past infancy, additional conditions become apparent. Limited growth, alopecia
, and a distinctive appearance with small face and jaw and pinched nose all are characteristic of progeria. Later the condition causes wrinkled skin, atherosclerosis
problems. Mental development is not affected. Individuals with the condition rarely live more than 17 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
predisposition. The people diagnosed with this disease usually have fragile elderly-like bodies.
Influences and references on or in popular culture
The movie Blade Runner featured a character named J.F. 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 ten 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 two 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 http://www.myspace.com/song4progeria Song For Progeria
In the popular sci-fi series Dark Angel, many of the transgenics suffer from progeria.
In season two of the popular youth sci-fi series " The Tribe" cases of a progeria-like disease are depicted. This 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 sixteen year old girl with progeria.
In the novel "The Magic Kingdom" by Stanley Elkin, a British man offers a dream vacation to Disneyland to six kids suffering from terminal diseases. One of the kids, named Charles Mudd-Gaddis, suffers from Progeria.
In the anime " Mobile Suit Gundam SEED", the character Rau Le Creuset has shortened telomeres due to genetic engineering that cause him to age at an accelerated rate. Without regular doses of a special medication, this causes him intense pain.
The season finale of " Bones" season two portrayed a murder victim afflicted with progeria.
In the second season of " The Fresh Prince of Bel-Air", Will Smith meets a character with progeria.
In Kage Baker's Company novels, it is repeatedly stated that there was an experiment in human cloning, but the clones developed progeria (apparently in the general sense of accelerated aging). The idea that clones would be subject to accelerated aging appears to have arisen from the reports that Dolly the sheep had shortened telomeres, which appears to be false.
In John Christopher's novel " Empty World", a pandemic described as similar to Hutchinson-Gilford syndrome causes the depopulation of Britain. The effects of the disease affecting small children mirror that of the progression of Progeria.
Accelerated aging disease
http://seattlepi.nwsource.com/specials/seth/190908_progeriamain.asp "A Time to Live" – Seattle Post-Intelligencer feature about Seth Cook, a child with Progeria.
http://seattlepi.nwsource.com/local/321200_seth26.html "Seth Cook, 1993-2007" – Seattle Post-Intelligencer obituary for Seth Cook.
http://www.channel4.com/health/microsites/0-9/80_year_old_children/index.html Bodyshock: The 80-Year-Old Children
http://www.mymultiplesclerosis.co.uk/misc/hayleyokines.html The Girl who is older than her Grandmother
http://news.bbc.co.uk/2/hi/south_asia/4286347.stm "Family tormented by ageing disease" – BBC News article on a family with Progeria; cites study that progeria is inheritable.
http://www.hgps.net Hutchinson-Gilford Progeria syndrome Network
http://www.hgps.net/media/ Media – a list of references in common culture
http://www.progeriaresearch.org/ Progeria Research Foundation
http://www.progeria.ca/ Progeria News and Media Collection
http://www.benbest.com/lifeext/aging.html#progeria Segmental Progeria
http://deltaboost.blogspot.com/2006/03/news-farnesyl-transferase-inhibitors.html Farnesyl transferase inhibitors may help children with Hutchinson-Gilford progeria – Article on the use of FTI inhibitors as potential treatment
Bu sayfa, online kullanıcı topluluğu tarafından oluşturulan ve düzenlenen özgür ansiklopedi projesi Wikipedia'nın Türkçe versiyonu Vikipedi'deki
maddesinden faydalanılarak veya ilgili madde birebir kopyalanarak hazırlanmıştır. Bu makale, GNU Özgür Belgeleme Lisansı
ilkeleri kapsamında, Vikipedi sitesindeki ilgili madde kaynak gösterilerek özgürce kullanılabilir.