limb if necessary. diseases commonly associated with werner syndrome such as diabetes and cancer are treated in generally the same ways as they would be for a non-werner syndrome individual. a change in diet and exercise can help prevent and control arteriosclerosis, and regular cancer screenings can allow for early detection of cancer. there is evidence that suggests that the cytokine-suppressive anti-inflammatory drug sb203580 may be a possible therapeutic option for patients with werner's syndrome. this drug targets the p38 signaling pathway, which may become activated as a result of genomic instability and stalled replication forks that are characteristic mutations in ws. this activation of p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. the p38 pathway has also been implicated in the inflammatory response that causes atherosclerosis, diabetes, and osteoporosis, all of which are associated with werner's syndrome. this drug has shown to revert the aged characteristics of young ws cells to those seen in normal, young cells and improve the lifespan of ws cells in vitro. sb203580 is in the clinical trial stages, and the same results have not yet been seen in vivo. in 2010, vitamin c supplementation was found to reverse the premature aging and several tissue dysfunctions in a genetically modified mouse model of the disease. vitamin c supplementation also appeared to normalize several age-related molecular markers such as the increased levels of the transcription factor nf-κb. in addition, it decreases activity of genes activated in human werner syndrome and increases gene activity involved in tissue repair. supplementation of vitamin c is suspected to be beneficial in the treatment of human werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice. in general, treatments are available for only the symptoms or complications and not for the disease itself. history otto werner was the first to observe werner syndrome in 1904 as a part of his dissertation research. as a german ophthalmologist, werner described several progeria-like features and juvenile cataracts in many of his patients. he noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of the syndrome at around the same age. he assumed the cause to be genetic, though most of his evidence was clinical. between 1934 and 1941, two internists from new york, oppenheimer and kugel, coined the term "werner syndrome," igniting a wave of interest and research on the disease. during that time, agatson and gartner suggested a possible link between werner's syndrome and cancer. however, it was not until 1966 that there was a general consensus on the autosomal recessive mode of inheritance for the syndrome. by 1981, geneticists had located the wrn gene on chromosome 8, leading to its cloning in 1996. this cloning of the wrn was significant because it revealed the predicted wrn protein was made from a family of dna helicases. prior to 1996, werner syndrome was thought to be a model for accelerated aging. since the discovery of the gene, it has become clear that the premature aging displayed in werner syndrome is not the same, on a cellular level, as normal aging. the role of wrn in dna repair and its exonuclease and helicase activities have been the subject of many studies in recent years. since the initial discovery in 1904, several other cases of werner syndrome have been recorded. many of these cases have occurred in japan, where a founder effect has caused a higher incidence rate than in other populations. the incidence rate of werner syndrome in japan is approximately 1 case per 100 thousand people (1:100,000), a large contrast with the rate of incidence for the rest of the world, which is between 1:1,000,000 and 1:10,000,000. a founder effect is also apparent in sardinia, where there have been 18 recorded cases of werner syndrome. society and culture on the episode "stargazer in a puddle" from the television series bones, the victim has werner syndrome. the team discovers in the course of the investigation that her mother killed her because she was dying of another disease, and worried that her daughter would have nobody to look after her afterwards, with the tragic twist that the mother began to recover from her disease after her daughter's death. werner syndrome is featured in the 1989 film the fly ii, starring eric stoltz, in which his character is born as a 2-year-old baby. he never sleeps and grows 5 times his normal age due to his biological father having half fly genes from the first 1986 film the fly. werner syndrome is also featured in the 1996 film jack, starring robin williams, in which his character ages four times faster than normal. in an early cutscene from the game metal gear solid 4, otacon cites "classic werner syndrome" as the most likely cause of solid snake's premature aging, though he goes on to say that testing had been inconclusive. it is however later said that solid snake's body, created as a genetically engineered clone, had been designed to break down quickly. in season 3 episode 9, "the ballad of kevin and tess", of the tv series the 4400, kevin is said to have werner syndrome to hide his real condition from the public. in the invisible man season 1 episode 6, "impetus", the new character gloria has an experimentally altered type of werner syndrome that causes it to become contagious. the central character in gail tsukiyama's novel dreaming water (2002) has werner's syndrome. in season 1 episode 8 "cold comfort" from tv series dark angel, a character has a "form of progeria, similar to werner syndrome", due to genetic manipulation. with an appropriate treatment, her condition seems to be stabilized. in resident evil: the final chapter (2016), the deadly "t-virus", which causes the viral pandemic in the resident evil film series, is revealed to be the cure for "adult progeria". james marcus originally develops the virus to cure his young daughter alicia marcus. ratsasan (2018), a tamil movie (as well as its telugu remake rakshasudu), features a young man born with werner's and is a victim of childhood bullying due to his appearance and has bad experience proposing to a girl, who turns into serial killer and hunts down and kills school girls. yashoda (2022), an indian movie, portrays the antagonist suffering from werner and using human foetuses to regain her beauty.