[9] Affected individuals typically grow and develop normally until puberty; the mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed.

[9][10] Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling, prematurely aged faces with beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles).

Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced fertility, bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels), atherosclerosis (blockage of blood vessels), type 2 diabetes, osteoporosis (loss of bone mass), telangiectasia, and malignancies.

[13] Gene transcription changes found in WS cells are strikingly similar to those observed in normal aging.

WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis.

[24] When functioning normally, the WRN gene and its associated protein (WRNp) are important for maintaining genome stability.

[30] Evidence was presented that WRN protein plays a direct role in the repair of methylation induced DNA damage.

This process likely involves the helicase and exonuclease activities of WRN protein that operate together with DNA polymerase beta in long patch base excision repair.

[7] Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates the function of p53, leading to a reduction in p53-dependent apoptosis and increasing the survival of these dysfunctional cells.

[33] Cells of affected individuals also have reduced lifespan in culture,[34] have more chromosome breaks and translocations[35] and have extensive deletions.

[36] Patients with Werner syndrome lose the RecQ helicase activity in the WRN protein because of the loss of its C-terminus region, but the mechanism by which this happens is unclear.

It is thought that the WRN helicase activity is important not only for DNA repair and recombination, but also for maintaining telomere length and stability.

[37] Without the WRN protein, the interwoven pathways of DNA repair and telomere maintenance fail to suppress cancer and the aging symptoms seen in patients with WS.

Events such as rapid telomere shortening cause Werner syndrome cells to exhibit low responses to overall cellular stress.

As a result, WS cells show a drastic reduction in replicative lifespan and enter into a stage of aging prematurely.

[39] WRN protein was found to have a specific role in preventing or repairing DNA damages resulting from chronic oxidative stress, particularly in slowly replicating cells.

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.

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.

[42] 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.

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.

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.

This is revealed to be the side effect of being a genetically engineered "test-tube baby", specifically made to be a clone of Big Boss (Metal Gear).

Solid Snake's genetic code was deliberately modified to make him rapidly age and die prematurely, to ensure he could not turn rogue against a powerful Shadow government (conspiracy theory) named "The Patriots".

Liquid Snake is the main antagonist of the 1998 entry in the franchise, Metal Gear Solid (1998 video game).

While not visually suffering from the effects of Werner's Syndrome, he is injected with a nanomachine-borne virus named "FOXDIE" that, over a long enough period of time, will cause rapid aging and premature death in the victim.

However, FOXDIE causes Liquid Snake to suffer from a fatal heart attack before he can live long enough to see the apparent effects of Werner's Syndrome.