While the bloom may be off the rose for resveratrol as a
miracle anti-aging molecule, there’s more to
the story. Spin-offs of this
wine-derived compound have recently been shown to reverse some fundamental
changes in cellular aging in ways that the parent compound doesn’t. Resveratrol
came to be a sort of celebrity molecule when it was demonstrated to activate
genetic “switches” called sirtuins, which mediate the lifespan-extending effects
of caloric restriction. But in the end it turned out that resveratrol is not a
direct sirtuin activator, and experiments in animals other than primitive
organisms failed to consistently replicate the effect. Resveratrol levels in
wine and other dietary sources are too low to explain wine’s association with
longevity anyway; secondly, when taken as a supplement it is rapidly
metabolized into other compounds. But the concept of activating anti-aging
genes opened new avenues of research, and new possibilities began to take
shape.
How splicing factors help keep cells youthful
A number of genes are progressively switched off as aging
progresses. Notable among these are the ones that code for enzymes called
splicing factors, which assemble the messenger molecules (mRNA) that in turn convey
the blueprint for protein building. Think of them as the wait staff at a
restaurant; if your DNA is the menu, the gene to be activated is the item
selected, the waiter (the mRNA) takes the order, which is then passed to the
kitchen for protein assembly. Splicing factors make sure the order is correct,
for example dressing on the side or no onions. Ensuring that orders are handled
correctly and consistently is vital to a successful restaurant, just as upkeep
of this cellular machinery is a critical step in maintaining health as we age. Degradation
of splicing factor function leads to metabolic dysfunction and eventual
shutdown, called senescence.
Resveratrol analogues activate splicing factors
The more senescent cells accumulate our tissues and organs,
the more they become susceptible to degenerative disease. This recent study,
from the Universities of Exeter and Brighton in the UK, found that resveratrol
analogues called resveralogues re-activated
splicing factor genes in human fibroblast cells in culture. Within hours the
cells became more active and even appeared healthier. (The research was widely
reported as a beauty breakthrough; while it follows that rejuvenated cells
might be associated with outward beauty, that’s a bit of a stretch at this
stage.)
Another specific feature of cellular aging may help explain
the effect of exposure to resveratrol-derived molecules. Chromosomes have end
caps called telomeres, sort of like the tips on shoelaces that prevent
unraveling. Telomeres shorten each time a cell divides, but exposure to the
resveratrol spinoffs appeared to lengthen them. This could mean that the number
of replicative cell cycles would be increased, overcoming a critical hurdle in
prolonging cell life. Restoring telomeres is one of the holy grails of
anti-aging, so if this could be replicated in human subjects it would be
revolutionary. That would be
beautiful thing indeed.
Wine cheers the sad,
revives the old, inspires the young, makes weariness forget his toil, and fears
her danger; opens a new world when this, the present, palls.
--Byron, Don Juan
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