Provides Opportunity to Extend Healthy Life Span: Mayo Clinic Study
Only 33% of mice with high levels of BubR1 developed
lung and skin tumors compared to 100% of the control group
Dec. 17, 2012 - The aging process is characterized
by high rates of whole-chromosome losses and gains in various organs,
including heart, muscle, kidney and eye, according to new work by Mayo
Clinic researchers. Reducing these rates slows age-related tissue
deterioration and promotes a healthier life span, they found in a study
of mouse models.
The findings appear in today's online issue of
Nature Cell Biology.
"We've known for some time that reduced levels of
BubR1 are a hallmark of aging and correspond to age-related conditions,
including muscle weakness, cataract formation and tumor growth," says
co-author Jan van Deursen, Ph.D., of Mayo Clinic.
"Here we've shown that a high abundance of BubR1, a
regulator of chromosome segregation during mitosis, preserves genomic
integrity and reduces tumors, even in the face of some genetic
alterations that promote inaccurate cell division. Our findings suggest
that controlling levels of this regulator provides a unique opportunity
to extend healthy life span."
Researchers studied two lines of transgenic mice,
one with moderate expression of BubR1 and the other with high
Outcomes of a series of experiments showed that
mice with high expression of the gene were dramatically effective in
preventing or limiting age-related disease compared to those with
moderate expression and especially to wild type mice.
The findings were significant. Only 33 percent of
these high expressing mice developed lung and skin tumors compared to
100 percent of the control group.
BubR1 overexpression markedly reduced aneuploidy (a
state of having an abnormal number of chromosomes), which causes birth
Other results showed these mice were –
● protected from muscle fiber deterioration,
● were better performers in treadmill tests, and
● had much reduced levels of renal sclerosis,
intestinal fibrosis and tubular atrophy - all signs of aging.
They also showed higher cardiac-stress tolerance
and resistance to age-related retinal atrophy.
Co-author Darren Baker, Ph.D., of Mayo Clinic, says
the findings show BubR1 and its associated regulators are "promising
targets for a broad spectrum of aneuploid human cancers and key
age-related disorders that dictate human health."
The research was supported by the National
Institutes of Health grant CA96985, the Ellison Medical Foundation, the
Noaber Foundation and the Robert and Arlene Kogod Center on Aging.
Co-authors include Meelad Dawlaty, Ph.D.; Karthik
Jegnathan; Liviu Malureanu, M.D.; Janine van Ree, Ph.D.; Ruben Crespo-Diaz,
Ph.D.; Santiago Reyes, Ph.D.; Lauren Seaburg; Virginia Shapiro, Ph.D.;
Atta Behfar, M.D., Ph.D., and Andre Terzic, M.D., Ph.D.; all of Mayo
Clinic; and Tobias Wijshake, and Bart van de Sluis, Ph.D., of the
University of Groningen, The Netherlands. Drs. Baker and Dawlaty are
joint first authors. Dr. van Deursen is the Vita Valley Professor of
Cell Senescence at Mayo Clinic and holds a joint appointment in the
Department of Pediatric and Adolescent Medicine and is chair of the
Department of Biochemistry and Molecular Biology. Dr. Terzic is the
Marriott Family Professor at Mayo Clinic.
About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in
medical care, research and education for people from all walks of life.
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