Additional evidence of caloric-restriction-induced neuro-protection:
http://groups.google.com/groups?selm=3d639051.132369978%40news.erols.comhttp://groups.google.com/groups?selm=3d5b0c65.105293614%40news.erols.comhttp://groups.google.com/groups?selm=3d5bb399.4916978%40news.erols.comhttp://www.napa.ufl.edu/2002news/localoriebrains.htm
UF STUDY: CALORIE RESTRICTION REDUCES AGE-RELATED BRAIN CELL DEATH
Dec. 30, 2002
GAINESVILLE, Fla. --- Trimming the waistline may not be the only
reason to cut calories after the New Year: Doing so also may protect
the brain from aging.
In the first study to look specifically at the effects of life-long
calorie-restricted diets on brain cells, University of Florida
researchers determined certain proteins linked to cell death that
naturally increase with age were significantly reduced in the brains
of rats whose calories were limited.
More important, they found the levels of a beneficial protein known to
provide potent protection against neuron death were twice as high in
older rats whose calories were restricted by 40 percent.
The findings could have significant implications not only for
alleviating the memory loss and other mental declines that accompany
normal aging, but also for a host of disorders related to excessive
loss of brain cells, such as Alzheimer's and Parkinson’s diseases,
which together afflict an estimated 4 million people in the United
States.
"In normal aging, there’s a variety of factors that could alter the
internal environment of the cell and make it more prone to die. We
would like to stop this," said Christiaan Leeuwenburgh, director of
the Biochemistry of Aging Laboratory at UF’s College of Health and
Human Performance. "Cells in neurons, muscle and heart have very low
regenerative capacity, so obviously you don’t want to lose a lot of
them."
The findings of his study, supported by grants from the National
Institutes of Health and the National Institute of Aging, are expected
to be published Jan. 2 in the online edition of the journal of the
Federation of American Societies for Experimental Biology.
The mechanisms of aging are complex, but as time passes, neurons of
the brain and central nervous system are thought to be increasingly
susceptible to apoptosis, a genetically programmed series of events
leading to cell death. Apoptosis can occur as a normal process to
destroy old cells so new ones can be made, or due to disease,
infection, damaged DNA or other maladies.
Based on decades of research in several species showing calorie
restriction not only boosted life span and general health but also
increased mental capacity, Leeuwenburgh and UF postdoctoral student
Rajani Shelke set out to determine if cutting calories also protected
aging neurons.
Understanding the reasons calorie restriction increases certain
neuroprotective proteins is important so that some day researchers may
be able to develop therapies to repair cells harmed in the disease
process or target genes to release additional amounts of these
proteins to ensure healthy life, said Leeuwenburgh, who also is
affiliated with UF’s Institute on Aging.
Mitochondria - the cells’ energy-producing centers - can be damaged by
free radicals or through calcium imbalances and other processes during
normal aging or as a result of disease. When that happens they release
proteins, most notably cytochrome c, that initiate cell death.
Using standard tests, Leeuwenburgh measured the levels of cytochrome c
and other indicators of apoptosis in the cytosolic fraction of the
frontal cortexes - areas important in learning and memory - of three
groups of rats: 12- and 26-month-old animals given unlimited food and
water, and a group of 26-month-old rats given 40 percent fewer
calories than those in the unrestricted groups. The animals in the
last group received food that was more nutritionally dense to ensure
they weren’t malnourished, a key concern about calorie-restricted
diets, Leeuwenburgh said.
The researchers found that cytochrome c, a natural protein that is
harmless until mitochondria become damaged, increased with age in the
normally nourished animals. In the 26-month-old, calorie-restricted
rats, however, the protein did not increase; instead, it remained at
the level of the young rats.
A novel protein the researchers focused on was ARC - or apoptosis
repressor with a caspase recruitment domain. They discovered that
while this beneficial protein, known to prevent the release of
cytochrome c and other destructive substances, dropped 60 percent with
age in the freely fed rats, levels of it increased over time in the
older calorie-restricted animals. These rats showed 40 percent more
ARC than in the young animals and 80 percent more than the older
unrestricted animals.
The study also found that specific DNA fragmentation, another
indicator of apoptosis, more than doubled in the unrestricted animals
over time, but were 36 percent less in the calorie-restricted rats.
Additional proteins called tumor necrosis factor and caspases 2 and 8
- dormant proteins that become destructive when activated by the onset
of apoptosis - also increased with age in the normally fed animals but
were relatively unchanged in those that had been restricted, the
researchers found.
In the future, Leeuwenburgh will explore other pathways that may play
roles in neuron death. "It’s a big puzzle, and we’re slowing putting
the pieces of the puzzle together, so to speak," he said.
While there are still many questions and major Western lifestyle
obstacles to overcome, calorie restriction provides significant health
benefits, even if started later in life, he said.
"We're not going to do it right away to improve our memories; we're
going to do it probably in general for the first reasons, which would
be to prevent cardiovascular disease and cancer," said Leeuwenburgh,
who is physically active and has moderately restricted his own calorie
intake for a decade. "And maybe it also has a protective effect - and
it's very suggestive in this study that it does - on brain function."
Noting the results are preliminary and that many questions remain
unanswered, Mark Mattson, chief of the National Institute on Aging’s
neurosciences laboratory, said, "The authors have made a new and
potentially important finding concerning the mechanism whereby caloric
restriction retards the aging process." If their discovery is valid,
he said, "the authors’ finding reveals a novel aging pathway that
could be targeted by other dietary manipulations or drugs."
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http://IanGoddard.net
"To lengthen thy life, lessen thy meals." Benjamin Franklin
Caloric Restriction: http://users.erols.com/igoddard/cr.htm
Ongoing CR-monkey-study update: "In the monkeys...those on
reduced feeding since the study started are dying at a rate
that is about half that of the monkeys receiving a full food
ration." Associated Press: Eating less may extend human life.
August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-
