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. Progeria is of interest to scientists because the disease may reveal clues about factors involved in 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.

Cause

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A 2006 paper 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 DNA and RNA synthesis. The common HGPS mutation results in the deletion of 50 amino acids from the Lamin A protein. DNA-damage signalling may be impaired by lamin A dysfunction, lending credence to the argument that genome instability is the common denominator of all the segmental progerias.

Prelamin A attaches to the nuclear membrane via a farnesyl lipid modification. Fong et al use a drug in a mouse model to inhibit protein farnesylation (farnesyltransferase inhibitor, or FTI). Treated mice had greater grip strength, lower likelihood of rib fracture and may live longer than untreated mice . A study which compared HGPS patient cells with the skin cells from 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. Nematodes over their lifespan show progressive lamin changes comparable to HGPS in all cells but neurons and gametes. These studies suggest that lamin A defects contribute to normal aging.

Symptoms

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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.

A cure for progeria has not yet been found.

Influences and references on or in popular culture

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• The movie Blade Runner featured a character named Sebastian who suffers from a Progeria-like disease which he refers to as "Methuselah Syndrome".
• 1994 on the 16th episode (Young at Heart) of the X-Files Tv-series a doctor has been able to create a method to reverse progeria to rejuvenate humans.
• In the science-fiction novel Otherland by Tad Williams, a young boy in his teenage years (Orlando Gardiner) is affected by progeria.
• The villain Ramon Salazar from the video game Resident Evil 4 suffered from Progeria.
• In 1996, the movie Jack tells the story of a 10 year old boy (Robin Williams) with an aging disorder much like Progeria.
• 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."

References

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See also

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

External links

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• "A Time to Live" – Seattle Post-Intelligencer feature about Seth Cook, a child with Progeria.
• Bodyshock: The 80-Year-Old Children
• "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

Aging | Gerontology | Genetic disorders | Rare diseases

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