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<http://www.sciencedaily.com/releases/2004/07/040707090939.htm>
Source:
Mayo Clinic
Date:
2004-07-07
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Mayo Clinic Researchers Identify Gene Regulating Aging And Fertility
ROCHESTER, Minn. -- Mayo Clinic researchers have discovered a gene
responsible for the onset of aging, including age-related disorders such
as infertility, reproductive problems and cataracts. This research,
conducted in genetically modified mice, is promising in helping
physicians understand and treat the same disorders in humans. The
findings appear in the July issue of the journal Nature Genetics.
[Baker, D.J. et al. (2004). Nat. Genet. 36, 744-749.
(http://www.nature.com/ng/)].
The discoveries came as the result of general investigations into
possible genetic causes of cancer. In this case, it was discovered that
this particular gene, called BubR1, governs production of a protein that
modulates physical aging. The mice studied lacked normal levels of that
protein and began to age prematurely.
"Darren Baker in our laboratory found that mutant mice with low amounts
of BubR1 protein live five times shorter than normal mice. They also
develop a variety of age-related disorders at a very young age," says
lead investigator Jan van Deursen, Ph.D., of the Mayo Clinic Departments
of Pediatric and Adolescent Medicine, and Biochemistry and Molecular
Biology.
Dr. van Deursen says, "This prompted us to investigate whether BubR1
protein levels go down as normal mice age naturally -- which is indeed
what we found. Based on these findings, we believe it is the decline of
this protein with time that may trigger some of the physiological
effects of aging."
Another Mayo investigator, Karthik Jeganathan, discovered that mice with
low amounts of BubR1 protein are infertile and unable to distribute
chromosomes properly when their germ cells divide. Abnormal numbers of
chromosomes in germ cells are a hallmark of reproductive aging in
humans, and the primary cause of increased still births and birth
defects, such as Down syndrome, in women over 35 years of age. Says Dr.
van Deursen, "Given the age-dependent decline in ovarian BubR1 in mice,
it seems reasonable to assume that this protein may contribute to
age-related infertility and certain birth defects in humans."
In collaboration with Mayo ophthalmologist J. Douglas Cameron, M.D., the
researchers discovered that mice with low amounts of BubR1 also develop
cataracts that are very similar to age-related cataracts in humans.
About 20 to 25 percent of individuals at age 65 and older have cataracts
of this type, and 1 million Americans undergo surgery to repair this
aging-related disorder each year.
In addition to Dr. van Deursen, other Mayo Clinic scientists involved in
the investigation were: Darren J. Baker; Karthik B. Jeganathan; J.
Douglas Cameron, M.D.; Michael A. Thompson; Subhash Juneja; Alena
Kopecka; Rajiv Kumar, M.D.; Robert B. Jenkins, M.D., Ph.D.; Piet C. de
Groen, M.D.; and Patrick Roche, Ph.D. The research was supported by a
grant from the National Institutes of Health.
Editor's Note: The original news release can be found here.
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This story has been adapted from a news release issued by Mayo Clinic.
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