New progress in understanding mechanism of aging:
a role for pyruvate supplementation?
Many decades ago it was noticed that lab animals put on very low-calorie diets lived substantially longer than those allowed
to eat freely. There have been various speculations about why such an anti-aging effect should occur — the most widely accepted
theory is that the metabolism of caloric substances gives rise to free radicals which damage cells and connective tissues,
making them function less well as the damage accumulates. Caloric restriction, a mild form of energy starvation, would therefore
reduce the metabolic rate and therefore decrease the damage cells receive from free radicals.
However, there are some problems with this explanation. Caloric restriction, like other forms of stress on cells, would be
expected to trigger in a controlled form of cell death called ‘apoptosis’ — a programmed response that preserves some cells
by killing others. In addition, starvation can shut down important cellular survival processes such as DNA repair. Yet these
destructive processes seem not to happen with caloric restriction.
Recent research is now beginning to shed light on these issues. For example, a group at Johns Hopkins has been studying a
known anti-aging gene called ‘SIRT1’. Working from the known fact that caloric restriction causes the SIRT1 gene to increase
its production of the ‘Sirt1’ protein, the researchers showed that the Sirt1 protein then signals the liver to synthesize
more glucose when glucose levels are low (as they would be during caloric restriction). The materials from which the liver
makes this glucose ultimately come from the body’s stored fats. This mobilization of fats may contribute to longevity by reducing
the potential for unsaturated fats to undergo chain-reaction oxidation to destructive free radicals.
It was also recently shown that the Sirt1 protein sets in motion a series of actions that inhibit apoptosis. This effect seems
to involve the stimulation of DNA repair enzymes.
The SIRT1 gene therefore serves as a nutrient sensor. It orchestrates cellular processes that counteract the deleterious effects
of starvation. It mobilizes fat stores to provide energy, causes damaged DNA to be repaired, and it prevents cell death.
Now here’s the most interesting part, from the standpoint of nutritional supplements: pyruvate levels are elevated during
starvation, and high pyruvate levels are used by cells as a signal to activate the SIRT1 gene. This leads to the notion that
if pyruvate levels can be sufficiently raised through the use of pyruvate supplementation, then the SIRT1 will be ‘fooled’
into thinking that the body is being starved and will act to counteract it. The liver would start drawing heavily on the body’s
fat deposits for energy production, and DNA repair enzymes would be mobilized to fix damaged DNA.
Pyruvate supplements have been available for quite some time. Have they shown benefits in agreement with the above theory?
Indeed, they have. Pyruvate supplements are widely used as fat-burners and energy enhancers. There is also evidence that pyruvate
protects cells from apoptosis resulting from DNA damage.
Link to news article:
Mouse study shows molecular connections between caloric restriction and lifespan extension
Link to commentary:
The 'Longevity' Gene
Link to research reports:
Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
The effects of pyruvate supplementation on body composition in overweight individuals.
NAD+ as a metabolic link between DNA damage and cell death.
LifeLink carries Pyruvate in 500 mg capsules and in 660 mg capsules.
Nutraceuticals and nootropics for anti-aging
