Created May 18th, 1996. Updated December 10th, 1996. Copyright by Duane Hewitt
The gene linked to Werner's syndrome has been reported cloned in a recent issue of Science. Werner's syndrome(WS) is an inherited disease that has symptoms that resemble premature aging. WS patients develop many age related diseases prematurely including arteriosclerosis, malignant neoplasms, type II diabetes mellitus, osteoporosis, ocular cataracts, early graying, loss of hair, skin atrophy, and aged appearance. However, not all age-related diseases are represented in WS patients. Notably absent are Alzheimer's disease and hypertension. The replicative lifespan of WS cells in culture is reduced relative to age-matched controls and is more similar to samples from older people. Most of those afflicted with this genetic defect die before age 50.
The gene associated with Werner's syndrome appears to be a DNA helicase. DNA helicases are known to be involved in the repair, replication and expression of the genetic material. The indicators of defective DNA metabolism in WS include chromosomal instability, elevated mutation rate at specific genes, elevated rates of nonhomologous recombination. WS cells do not show an increased susceptibility to ultraviolet exposure or other DNA damaging agents therefore there is no defect in these DNA repair mechanisms.
With the cloning of this gene the mechanisms underlying Werner's syndrome can now be attacked. This effort was undertaken in collaboration with Darwin Molecular Corporation(great name!) of Seattle. To find this gene over 650,000 bases were sequenced which is the largest number to date involved in the cloning of a single gene. This gene was shown to be a helicase by a sequence homology but this has not yet been proven directly. This discovery raises the question as to whether normal people have versions of this gene that affect their life-span. Of course this also leads to the possibility that this gene can be reengineered to extend lifespans in a significant manner.
The cloning of the Werner's syndrome gene is significant in that it indicates that a single gene can have a large effect upon the aging process. The fact that this gene is involved in DNA metabolism is intriguing. This discovery gives us a compass to follow in determining the first system to bread down during aging which very well may be the level of DNA replication. This may also relate to the Hayflick limit which is the observation that mammalian cells in tissue culture divide only a limited number of times. However much of this speculation is premature until the Werner's gene product is characterized and cells constructed with mutant proteins. One great experiment would be to see if cells with a reengineered version of the Werner's gene product could extend cell viability past the Hayflick limit.
To forward information or give feedback: duane@immortality.org