Aging is the main risk factor for Alzheimer’s disease, but the aspects of the aging process
that predispose the brain to develop Alzheimer’s are largely unknown. Now researchers
at the College of Medicine have made an exciting new discovery about the reason why
brain cells deteriorate so rapidly in people with Alzheimer’s disease. And they hope that
this discovery may ultimately translate into effective treatment for the 36 million people
who suffer from the disease worldwide.
During a two-year study led by Claudio
Torres, Ph.D., assistant professor in the
Department of Pathology & Laboratory
Medicine, and published online in the
September 12, 2012, issue of PLoS ONE*,
the research team found that senescence, a
natural mechanism the body uses to protect
against cancer, could be an important
component in Alzheimer’s disease.
When senescence occurs, biological
changes stop cells from dividing as they
normally do and switch them into producing
toxic proteins that seem to trigger inflammation.
“Senescence is good when you’re young
because it’s a protective mechanism against
cancer, but as you get older, and the senescent
cells continue to produce toxins, inflammation
occurs, which is especially bad for the
brain,” says Torres, whose research has been
inspired in part by his mother, who suffers
from Alzheimer’s disease.
Cellular senescence has been studied
previously in other body tissues, but Torres’s
research group is the first to study senescence
in the brain. Other group members from the
Department of Pathology & Laboratory
Medicine include Rekha Bhat, M.D., a former
resident; graduate students Elizabeth Crowe
and Alessandro Bitto; Michelle Moh, a
medical student; and faculty members Drs. Christos D. Katsetos, professor; Fernando
Garcia, professor; and Christian Sell, associate professor. There were also two collaborators
from the University of Pennsylvania.
For the first time, Torres and his team demonstrated that senescence occurs in the
astrocyte cells of the brain. These star-shaped cells, which make up about 80 percent of
the brain, perform many vital functions in the central nervous system to maintain homeostasis
and support the neurons. Unlike neurons, astrocytes divide, which led Torres to
hypothesize that senescence might be at play in the brain.
The research team studied post-mortem brain samples from fetuses; adults aged 35 to 50; and adults aged 78 to 90. They found that healthy
brains from adults over 35 had six to eight times more
senescent cells than the fetuses. In the oldest group, they
studied subjects with and without the presence of Alzheimer’s
disease and discovered that
adults with Alzheimer’s had 10
percent more of these cells than
Torres and his colleagues noted
factors secreted by senescent cells
that cause inflammation, long
thought to contribute to Alzheimer’s
“Senescent cells secrete a large
volume of cytokines, particularly
interleukin-6, which is known to be
increased in the brains of Alzheimer’s
patients,” he relates. “Before
this discovery, no one knew exactly
where the inflammatory proteins
were coming from. Now we
suggest that they are coming from
senescent astrocytes. This has
opened a new window on
Torres and his group also studied
the relationship between senescence and beta amyloid
protein plaques found in the brains of people with Alzheimer’s.
When they put beta amyloid in petri dishes filled with
young astrocytes, the cells began to senesce within five days.
“Beta amyloid clearly acts as a stressor, causing more
astrocytes to senesce,” says Torres.
What can be done to prevent this?
Preventing senescence is probably not the best solution
because it may increase the risk of cancer, according
“Rather than preventing senescence, our main goal
now is to eliminate senescent cells
through the immune system. This is
the main focus of the next phase of
our research,” he says.
Torres notes that a study published
last year reported the first clinical
evidence that elimination of all
senescent cells in the body of a mouse
improved lifespan and prevented
diseases of aging.
“We hope to show that the same
can be achieved in brain cells,” he
says. “Then we can begin the path
toward translation, perhaps an
enzyme-based drug that will stop the
toxic inflammatory secretions that
occur in senescence. If we can
eliminate senescent cells, or their
pattern, we may be able to mitigate
signs and symptoms associated with
“After almost 50 years of research with no cure for
Alzheimer’s, we are excited by the potential,” he concludes.
*“Astrocyte Senescence as a Component of Alzheimer’s Disease” in PLoS
ONE 7(9): e45069. doi:10.1371/journal.pone.0045069 at plosone.org.
This article originally appeared in the February/March 2013 issue of Pulse, the newsletter of Drexel University College of Medicine.