Resveratrol derivatives reverse signs of cellular aging – next beauty breakthrough?

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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