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A Closer Look at Intrinsic Aging

By: Steve Herman
Posted: April 7, 2009, from the April 2009 issue of GCI Magazine.

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Sophisticated cosmetics try to turn back the clock, but what exactly is the clock and how far back can it be turned? It is clear that an 80-year-old woman, regardless of her health and beauty regimen, cannot look like a 16-year-old girl. The October 2008 issue of Scientific American2 contained an article titled, “Rethinking the Wrinkling: Key genes, rather than cell and DNA damage, as causes of aging,” summarizing work published in Cell, a journal of research in molecular biology, biochemistry and cell biology, on nematode worms—commonly used in the genetic study of aging. The lifetime of worms can be extended by gene manipulation, and there are analogous mechanisms present in humans. The Cell paper3 referred to in Scientific American reports on the influence of ELT-3, ELT-5 and ELT-6 on GATA transcription circuits, which have been shown to be responsible for age-regulation, and so to the intrinsic aging of the nematode worm.

Cell culture research into the behavior of the human sirtuin SIRT1, an enzyme that deacetylates proteins that contribute to cellular regulation, shows that it behaves much like yeast sirtuin Sir2 (SIRT2), which assists in the repair of DNA and regulates genes connected with aging. The effects of aging may be partly due to SIRT2 being increasingly diverted to repair DNA damage.

CBS television’s 60 Minutes also touched on the sirtuin gene in a segment titled “Fountain Of Youth In A Wine Rx?” that originally aired on Jan. 25, 2009. Researchers featured in the segment hypothesized that, when active, the sirtuin gene triggers a survival mechanism that extends life. Their search for natural compounds that trigger sirtuin led them to resveratrol, which is found in relatively large amounts in red wine. Cosmetic applications were coming into the fore in 2008,5, 6 and products have been entering the market. Among the higher-profile offerings, Avon offered Anew Ultimate, powered by pro-sirtuin TX, while Estée Lauder marketed Re-Nutriv Ultimate Youth Creme with SIRT1.

On the supplier side, several ingredients in addition to resveratrol are positioned for sirtuin activity. The research being done with sirtuins does not involve applying SIRT1 in a cream—the molecules are too large to penetrate the skin and in any case would likely be rejected by the body. The current approach involves finding compounds, primarily peptides, that promote activity of the body’s own sirtuin. Christian Dior Capture Totale Multi-Perfection Cream utilizes the pro-sirtuin activity of Kluyveromyces yeast biopeptide. In more romantic terms, it uses Longoza—a rare plant grown only in Madagascar.

Chemicals can also inhibit sirtuin production, as has been shown for dihydroxycoumarin.6 But that’s not good, and the implication for cosmetic formulations is profound. If some materials can activate sirtuin and others can deactivate it, it would be necessary to know the potential activity of every ingredient. In fact, materials that specifically target sirtuin are fairly rare—that’s why resveratrol is so special. But moving forward, expansion of the database of these materials is clearly imperative.

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