Foundation, NJ U. S. A
Eat Less, Live Healthier and Longer,
but Preserve the Meaning of Life and
restriction, involves eating about 30 percent fewer calories
than normal while still getting adequate amounts of
vitamins, minerals and other nutrients. Aside from direct
genetic manipulation, calorie restriction is the only
strategy known to extend life consistently in a variety of
In the last
year, calorie-restricted diets have been shown in various
animals to affect molecular pathways likely to be involved
in the progression of Alzheimer's disease, diabetes, heart
disease, Parkinson's disease and cancer. Earlier this year,
researchers studying dietary effects on humans went so far
as to claim that calorie restriction may be more effective
than exercise at preventing age-related diseases.
cast doubt on long-held scientific and cultural beliefs
regarding the inevitability of the body's decline. They also
suggest that other interventions, which include new drugs,
may retard aging even if the diet itself should prove
ineffective in humans. One leading candidate, a newly
synthesized form of resveratrol -- an antioxidant present in
large amounts in red wine -- is already being tested in
patients. It may eventually be the first of a new class of
anti-aging drugs. Extrapolating from recent animal findings,
Dr. Richard A. Miller, a pathologist at the University of
Michigan, estimated that a pill mimicking the effects of
calorie restriction might increase human life span to about
112 healthy years, with the occasional senior living until
140, though some experts view that projection as overly
In almost every
instance, the subjects on low-calorie diets have proven to
be not just longer lived, but also more resistant to
"In mice, calorie restriction doesn't just extend life
span," said Leonard P. Guarente, professor of biology at the
Massachusetts Institute of Technology. "It mitigates many
diseases of aging: cancer, cardiovascular disease,
neurodegenerative disease. The gain is just enormous."
Louisiana State University reported in April in The Journal
of the American Medical Association that patients on an
experimental low-calorie diet had lower insulin levels and
body temperatures, both possible markers of longevity, and
fewer signs of the chromosomal damage typically associated
These studies and others have led many scientists to
believe they have stumbled onto a central determinant of
natural life span. Animals on restricted diets seem
particularly resistant to environmental stresses like
oxidation and heat, perhaps even radiation. "It is a very
deep, very important function," Dr. Miller said. Experts
theorize that limited access to energy alarms the body, so
to speak, activating a cascade of biochemical signals that
tell each cell to direct energy away from reproductive
functions, toward repair and maintenance. The
calorie-restricted organism is stronger, according to this
hypothesis, because individual cells are more efficiently
repairing mutations, using energy, defending themselves and
mopping up harmful byproducts like free radicals.
"The stressed cell is really pulling out all the stops"
to preserve itself, said Dr. Cynthia Kenyon, a molecular
biologist at the University of California, San Francisco.
"This system could have evolved as a way of letting animals
take a timeout from reproduction when times are harsh."
In a series of studies, Dr. Kenyon, of the University of
California, San Francisco, has created mutant roundworms
that live six times longer than normal, largely because of a
mutation in a single gene called daf-2. The gene encodes a
receptor on the surface of cells similar to a receptor in
humans that responds to two important hormones, insulin and
the insulin-like growth factor 1 or IGF-1.
Insulin is necessary for the body to transport glucose
into cells to fuel their operations. Dr. Kenyon and other
researchers suggest that worm cells with mutated receptors
may be "tricked" into sensing that nutrients are not
available, even when they are. With its maintenance
machinery thereby turned on high, each worm cell lives far
longer -- and so does the worm.
Many experts are now convinced that the energy-signaling
pathways that employ insulin and IGF-1 are very involved in
fixing an organism's life span. Some researchers have even
described Type 2 diabetes, which is marked by insensitivity
to the hormone insulin, as simply an accelerated form of
In yeast, scientists have discovered a gene similar to
daf-2 called SIR2, that also helps to coordinate the cell's
defensive response once activated by calorie restriction or
another external stressor. The genes encode proteins called
sirtuins, which are found in both plants and animals.
A mammalian version of the SIR2 gene, called SIRT1, has
been shown to regulate a number of processes necessary for
long-term survival in calorie-restricted mice.
Scientists are now trying to develop synthetic compounds
that affect the genes daf-2 and SIRT1.
Several candidate drugs designed to prevent age-related
diseases, particularly diabetes, are on the drawing boards
at biotech companies. Sirtris Pharmaceuticals, in Boston,
already has begun testing a new drug in patients with Type 2
diabetes that acts on SIRT1 to improve the functioning of
mitochondria, the cell's energy factories.
While an anti-aging pill may be the next big
blockbuster, some ethicists believe that the all-out
determination to extend life span is veined with arrogance.
As appointments with death are postponed, says Dr. Leon R.
Kass, former chairman of the President's Council on
Bioethics, human lives may become less engaging, less
meaningful, even less beautiful.
Dr. Kass recently wrote. "Mortality makes life matter."
courtesy: Dr. Robert Crane