Clearing Out 'Old Cells' Might Make for Healthier Old
WEDNESDAY, Nov. 2 (HealthDay News) -- Sweeping away the body's
old cells may help delay age-related health woes and give more pep
to old age, a new study in mice suggests.
In a study published online Nov. 2 in
Nature, Mayo Clinic scientists came up with a way to eliminate so-called "senescent" cells -- aging cells that stop functioning properly but still stick around the body, damaging healthy tissues, explained study author Dr. Jan van Deursen, a professor of pediatrics, molecular biology and biochemistry at the Mayo Clinic in Rochester, Minn.
"This research has identified a cell class that makes you old and makes you have age-related declines. We can now start to think about how you can get rid of them," he said.
According to van Deursen, "how organisms and people age is not
really well understood, particularly not at a cell and molecular
level. There are many theories about how we age and one of the
theories that we investigated was that as we age, senescent cells
start to accumulate and produce and secrete proteins and other
factors that basically make the healthy neighboring cells that
surround them less functional."
After "deleting" senescent cells in mice genetically engineered
to age quickly, tissues remained healthier and performed better,
van Deursen's team found.
Senescent cells are limited in number, making only up to 15
percent of cells in an elderly person, for example. To eliminate
them in the mice, the researchers focused a tracer on a protein
called p16, explained co-author Dr. James Kirkland, director of the
Mayo Clinic's Robert and Arlene Kogod Center on Aging.
P16 stops cells from dividing and can trigger a series of steps
that causes cellular senescence, Kirkland said.
"In healthy young cells the p16 gene is not expressed," van Deursen added. "Later on, as we age, it becomes higher in our tissues."
The scientists used p16 to activate a type of "suicide gene"
within senescent cells. The protein made by this gene will kill
senescent cells (without harming other normal cells) after a drug
specifically designed to activate it is administered, said van
Two sets of prematurely aged mice were involved. In one set, the
researchers cleared senescent cells for the whole 15 months of the
mice's typical lifespan. In another set of mice, they waited until
age-related problems were well underway and then cleared the
senescent cells away for a few months, said Kirkland.
The result: Lifelong destruction of a mouse's senescent cells
kept age-related problems at bay, including cataracts and loss of
muscle mass and strength. But the study also suggested that
removing senescent cells later in life could slow down these
age-related health problems.
What's more, said Kirkland, improved behavior was noted -- the
activity level of the mice was considerably higher.
Still, the research is early and has not yet moved into
experiments in humans. "It's a proof of principle study. Now we
know we can safely remove these cells in an animal model without
causing any detectable harm," said van Deursen.
Dr. Gary Kennedy, director of the Division of Geriatric
Psychiatry at Montefiore Medical Center in the Bronx, and an expert
in aging, said the work was exciting.
"When they blocked the senescent cell process in mice prone to premature aging, they blocked the development of spinal arthritis, the loss of muscle, thinning of skin -- they were all reversed. Mice that should have looked prematurely aged were essentially normal," Kennedy noted. But he stressed that the research needs to be replicated in other species as well before the public gets excited about its medical promise.
"I thought it was a very interesting paper. I was actually surprised by the data -- no one else has been able to do this," added Dr. Julian Sage, an associate professor of pediatrics and genetics at Stanford University. He said the "genetic trick" they used to eliminate the cell was intriguing, and he was equally interested in the finding that when you clear senescent cells that damage is curtailed.
Sage said the next big question is how to determine when and how
many senescent cells to remove to have a positive health
"The tricky part in people will be how many senescent cells you can eliminate without killing the person, but to have an effect," Sage believes.
Another expert agreed the findings were intriguing.
"It's an elegant study and a most important discovery," said Dr. Nir Barzilai, professor of medicine and genetics and director of the Institute for Aging Research at Albert Einstein College of Medicine, in New York City. He said it's been suggested that senescence is a protective mechanism, against cancer, for example. However, "this paper really suggests that senescence is not good or neutral, but in fact, if cleared, can be associated with less aging," he said.
The findings invite countless avenues for future research, said
"If you attack the fundamental aging process, can you attack age-related illnesses as a whole?" Kirkland wondered. "Can you delay cancer, dementias, atherosclerosis, diabetes, obesity and its complications as a group?"
For tips on healthy aging, head to the
U.S. Centers for
Disease Control and Prevention.
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