The elixir of life could soon became a scientific reality
as the researchers from Harvard Medical School, in collaboration with
scientists from Cornell Medical School and the National Institutes of Health
reported the discovery of two genes in mammalian cells that act as gatekeepers
for cellular longevity.
The fact that the caloric restriction prolongs life has been
a scientific fact for almost 70 years, but only now the scientists has started
to study the molecular mechanism that links the low-caloric diet to longevity.
In their research, published in the September 21 issue of
the journal CelL, the scientists concluded that the caloric restriction is in a
fact a stress for the cells to which they respond by activating two protective
genes.
The scientific team was lead by David Sinclair, associate
professor of pathology at Harvard
Medical School
and senior author on the paper.
According to their findings the two genes, called SIRT3 and
SIRT4, play a vital role in a longevity network that maintains the vitality of
mitochondria and keeps cells healthy when they would otherwise die.
But why is the mitochondria, a kind of cellular organ that
lives in the cytoplasm, so important for the cell life?
The mitochondria are considered to be the cell's battery
packs and when its stability starts to wane, energy is drained out of the cell,
and its days are numbered.
According to Sinclair’s team, when the cells undergo caloric
restriction, signals sent in through the membrane activate a gene called NAMPT
(nicotinamide phosphoribosyltransferase). As levels of NAMPT ramp up, a small
molecule called NAD begins to amass in the mitochondria. This, in turn, causes
the activity of enzymes created by the SIRT3 and SIRT4 genes - enzymes that
live in the mitochondria--to increase as well. As a result, the mitochondria
grow stronger, energy-output increases, and the cell's aging process slows down
significantly.
"Mitochondria are the guardians of cell survival,"
explained Sinclair. "If we can keep boosting levels of NAD in the
mitochondria, which in turn stimulates buckets more of SIRT3 and SIRT4, then
for a period of time the cell really needs nothing else."
In fact, the mitochondria appear to be so essential to the
cell's life that when all other energy sources inside the cell-including the
nucleus-are wiped out, yet the mitochondria are kept intact and functional, the
cell remains alive.
“These two genes, SIRT3 and SIRT4, they make proteins that
go into mitochondria. These are little energy packs inside our cells that are
very important for staying healthy and youthful and, as we age, we lose them
and they get less efficient,” Sinclair said.
According to scientists, the exercises may also boost SIRT 3
levels. "I think SIRT3 is the next most interesting sirtuin from a drug
development standpoint," Sinclair says. "It does protect cells, but
there's growing evidence that it may mediate the benefits of exercise as
well."
Still the scientist has to determine what is the particular
mechanism activated by these increased levels of NAD, and as a result SIRT3 and
SIRT4, but they are sure that events leading to cell death are at the very
least delayed when there are vast quantities of the enzymes.
In fact, SIRT 3 and SIRT 4 are members of the recently-discovered
family of enzymes that promote the body's natural defense against disease.
There are seven human sirtuins (SIRT1-7).
Last year, in another study, it was proved that SIRT 1 have
a powerful impact on longevity when stimulated by the red-wine molecule
resveratrol.
What is more important is that these two genes may be
potential drug targets for diseases associated with aging.
"Theoretically, we can envision a small molecule that
can increase levels of NAD, or SIRT3 and SIRT4 directly, in the
mitochondria," says Sinclair. "Such a molecule could be used for many
age-related diseases."
Dave Sinclair is also a co-founder of Sirtris
Pharmaceuticals, which is developing drugs that target SIRT genes by miming
certain beneficial health effects of calorie restriction, without requiring a
change in eating habits.