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A Closer Look at Intrinsic Aging

Steve Herman

“Time may be a great healer, but it’s a lousy beautician.” — Lucille S. Harper

The formulation of antiaging products presupposes an understanding of aging itself, a subject given a thought provoking spin in F. Scott Fitzgerald’s short story The Curious Case of Benjamin Button, recently made into a major motion picture. Putting the aging clock in reverse is the ultimate goal of cosmeceuticals, but there are many mysteries of aging yet to be unlocked. All we know with certainty is that there are two primary types of aging: intrinsic and extrinsic.

Sometimes sophisticated instrumentation is needed to test skin properties, but not in the case of intrinsic versus extrinsic aging. Compare skin that is, for the most part, always covered to skin that is always exposed. The two areas are the same chronological age; the evident difference is the result of extrinsic aging.

Contrast that to intrinsic aging.

Martin Rieger wrote a comprehensive article on the subject in 1995.1 There are simple and well-established rules to minimize intrinsic aging—avoid sun and smoking, for example— and functional products usually contain UV protection, antioxidants and free radical scavengers that provide a common-sense first line of defense.

Aging at the Cellular Level

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.

Outpacing Science Fiction

If the likelihood of finding real age-defying ingredients seems far-fetched, consider the advancements that would have been relegated to the realm of science fiction not too long ago. One finds that real science is outpacing science fiction at an accelerated rate. For example, if amblyopia (“lazy eye”) is left untreated past a critical stage it becomes untreatable because the critical brain wiring becomes fixed. Recent neuroscience research in rats, however, showed the possibility of turning the brain back into a plastic state, where rewiring can be done. In essence, an old brain could be made like a young brain for treatment of conditions such as amblyopia.

In the field of skin care, it seems like only yesterday that DNA repair enzymes and rousing stem cells in the basal epidermal membrane were cutting-edge. Now the mysteries of aging are being peeled away daily in laboratories around the world, with the results disclosed instantly on the Web. In a world where miracles become realities at the genetic scale, the future potential for antiaging products is mind-boggling.


  1. M Rieger, Intrinsic Aging, Cosm&Toil, 100 94–101 (1995)
  2. M Wenner, Rethinking the Wrinkling: Key genes, rather than cell and DNA damage, as causes of aging, Sci Am (Oct 2008)
  3. Budovskaya et al., An elt-3/elt-5/elt-6 GATA Circuit Guides Aging in C. Eegans, Cell (2008) Doi:10.10.1016/j.cell.2008.05.044.
  4. B Brewster, Stimulating Sirtuins Antiaging Appeal, Cosm&Toil 123 22–29 (2008)
  5. I Imbert et al., Sirtuins: A Breakthrough in Antiaging Research, Cosm&Toil 123 69–74 (2008)
  6. AJ Olaharski, J Rine, BL Marshall, J Babiarz, L Zhang, et al., The Flavoring Agent Dihydrocoumarin Reverses Epigenetic Silencing and Inhibits Sirtuin Deacetylases, PLoS Genet 1(6):e77 (2005)

Steve Herman is president of Diffusion LLC, a consulting company specializing in regulatory issues, intellectual property, and technology development and transfer. An adjunct professor in the Fairleigh Dickinson University Masters in Cosmetic Science program, his book, Fragrance Applications: A Survival Guide, was published by Allured Publishing Corp. in 2001. A former chairman of the SCC’s New York chapter, he was elected to fellow status in 2002.

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