Slowing Intrinsic and Extrinsic Aging: A Dual Approach

May 1, 2009 | Contact Author | By: Liki von Oppen-Bezalel, IBR Ltd.
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Title: Slowing Intrinsic and Extrinsic Aging: A Dual Approach
antiagingx photoagingx intrinsic agingx extrinsic agingx cell proliferationx oxidationx dorminsx colorless carotenoidsx
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Keywords: antiaging | photoaging | intrinsic aging | extrinsic aging | cell proliferation | oxidation | dormins | colorless carotenoids

Abstract: In this dual approach to antiaging, intrinsic factors are first addressed by slowing cell proliferation in skin via a technology based on dormins—in this case, extracts from dormant Narcissus tazetta bulb. Then, to protect against extrinsic aging, colorless carotenoids are employed to absorb UV radiation and prevent oxidative stress damage.

When designing products for maximum antiaging benefits, formulators should consider both intrinsic and extrinsic aging factors—intrinsic being naturally programmed aging, and extrinsic resulting from accumulated damage. This article describes a combined approach to reduce the signs of aging, the first of which focuses on intrinsic aging by slowing cell proliferation rate to preserve cells in their younger stage. The second approach aims at extrinsic factors to protect the skin from photo- and oxi- dative damage. 

Intrinsic Aging

Intrinsic aging is, in a way, programmed aging that is regulated by a cell’s internal clock that defines the number of replications a cell can endure as it ages.1, 2 This is based on Hayflick’s theory stating that cells have a limited capacity to replicate. With recent elucidation of the respective role of telomeres and telomerase, the Hayflick theory has been strongly supported in the scientific community. Consequently, there are at least two ways to delay intrinsic aging: by slowing proliferation and extending the cell cycle, or by preventing telo-mere shortening. 

The slowing of cell proliferation can be accomplished via the concept of dormancy. Dormancy is a natural state that plants and some animals enter to protect themselves from unfavorable environmental and growth conditions. Once more favorable conditions are present, these entities are able to rejuvenate themselves. During dormancy, however, growth functions are slowed and cell proliferation is inhibited. Flower bulbs are a good example; they go dormant through the winter season and emerge as beautiful, rejuvenated blossoms in the spring.

Inhibition of cell proliferation during dormancy is achieved through dormins. However, the chemical nature of these entities varies between plants and organisms, which is why it has been difficult to determine their mechanism of action beyond reversing growth arrest. Once dormins are removed, cell growth resumes; thus dormins are a favorable approach to treat intrinsic aging since they are cell proliferation inhibitors. Further, it is known3 that UV and oxidative stress can cause enhanced proliferation (i.e., cancer), leading to premature aging. Therefore, slowing this proliferation process could not only preserve the cell youth capital, but also slow the effects of premature aging.4–10 

Researchers recently have developed several technologies based on a natural extract derived from plants during their dormant stage. These dorminsa were shown to slow cell proliferation in a demonstration using germinated cucumber seeds.

Dormins and seed root elongation: Extracts taken from dormant and nondormant Narcissus tazetta bulbs were applied to germinated cucumber seeds to examine their effects on seed root elongation (see Figure 1). 

The length of roots and hypocotyls of the germinated seed were measured for several days. Results reflected a dose-response curve where the higher concentration of extract matched with the shortest length of roots and hypocotyls, indicating less growth and cell proliferation. 

Similar effects were observed by counting cells in a cell culture. Methods to examine these effects are protected under copyright, but it can generally be stated that comparing dormant and nondormant extracts clearly showed the slowing of cell proliferation in the presence of dormins, while no such effect was observed with extracts from the nondormant plant. Interestingly, a similar effect was shown on normal human keratinocytes (see Figure 1).

Materials and Methods

To demonstrate the antiaging benefits of a dormant extract on skin cell proliferation, a placebo-controlled, double blind study was conducted with a cream containing Narcissus tazetta bulb extract at 0.5% and 1.5%, and a control cream excluding the extract. An example of a similar cream is shown in Figure 3.

A total of 135 female panelists was divided into three groups and given one of the three sample creams to test. Subjects rated the performance of their skin in relation to various parameters on a 10-cm nonscaled ruler, as is described below, before they initiated the twice daily application of a respective cream (T0). The same rating was performed at the end of the study (day 28) on a new nonscaled ruler (T28). Researchers found that the creams containing the extract at 1.5% were rated significantly higher than the placebo. This was particularly true for the perception of skin’s resistance to the environment and protective capabilities in addition to skin sensitivity and irritability (see Figure 2). 

These results support the hypothesis that the dormant extracts could slow the proliferation of cells to allow the epidermis time to fully develop into a healthier-looking, more complete skin layer including defenses to protect the skin against environmental stressors. 

Besides antiaging, slower cell turnover can provide other benefits. For instance, slowing intrinsic aging prolongs the appearance of artificially tanned skin since corneocytes shed less quickly and therefore maintain a tan for longer periods of time.11 And provided that hair follicle cells may also respond to the dormant extracts, dormins could slow the growth of hair. Sebaceous cells or adipocytes may also be interesting targets.

Extrinsic Aging

Besides intrinsic aging, extrinsic factors cause skin aging. Extrinsic aging is affected by environmental stresses including reactive oxygen species (ROS), UV irradiation and free radicals that contribute to accumulated damage, and collagen and cell matrix degradation. In general, a free radical is any molecule that has a single unpaired electron in its outer shell. While few free radicals are stable, most biologically relevant free radicals are fairly reactive and for most biological organisms, free radical damage is closely associated with oxidative damage.

Based on Harman’s free radical theory of aging stating that organisms age because cells accumulate free radical damage over time,12–15 antioxidants are commonly used in skin care to fight aging. One such antioxidant recently was developed based on colorless carotenoidsb.

It is important to note that, while they are important to use, sunscreens can also increase an individual’s exposure to environmental stresses such as free radicals that lead to premature aging. Since sunscreens protect against UVB and reduce erythema formation, they also allow consumers to stay in the sun longer without immediate visible signs of damage. Longer exposure to UV irradiation increases the chances of free radical generation.

The colorless carotenoids phytoene and phytofluene (P&P) are natural carotenoids that lack visible color due to their lower number of conjugated double bonds on the C40 carbon backbone of the molecule. This structure allows them to absorb light in the UVA and UVB range and quench the free radicals formed by UV light—with or without the presence of sunscreens.16

These colorless carotenoids have also shown good antioxidant capacity against hydroxyl radicals.17,18 These capabilities, among others, enable them to reduce damage to DNA and collagen degradation while reducing inflammation.17–20 Thus, the addition of the P&P to sun protection formulas could reduce the risk of skin damage, as was previously shown.16 Two sunscreen creams were prepared, one containing 5% Dunaliella salina extract, which is an extract of P&P from algae, and one without the extract used as control. The SPF of both sunscreens was measured in vitro by applying a 2 mg/m2 sample of the test creams to a skin substrate and irradiating it. The reflected light was measured, the Minimum Protection Factor (MPF) was obtained, and the SPF was calculated, revealing a significantly higher SPF level in the presence of the Dunaliella salina extract (see Table 1).


The two primary mechanisms of aging—i.e., intrinsic and extrinsic—can be targeted together to provide a dual approach to antiaging. By slowing cell proliferation to maintain youth capital in cells, and protecting against UV damage and free radicals with antioxidants, internal and external aggressions can be counteracted. This dual approach provides a tool that may slow aging more comprehensively, preventing the formation of skin disorders that result from pre-matured extrinsic as well as intrinsic aging. The skin is thus provided with a defense and prevention tools to keep it healthier, younger-looking and better able to shield the body, fitting its basic function. 


1. AG Bondar et al, Extension of life span by introduction of telomerase into human cells,Science 279 349–352 (1998)

2. KH Buchkovich, Telomeres, telomerase and cell cycle, Prog Cell Cycle Res 2 187–195 (1996)

3. Ichihashi et al, UV-induced skin damage, Toxicology 189, 1–2: 21–39 (2003) 

4. L Hayflick and PS Moorhead, The serial cultivation of human diploid cell strains, Exp Cell Res 25 585–621 (1961)

5. L Hayflick, Current theories of biological aging, Fed Proc 34 9–13 (1975)

6. L Hayflick, The cell biology of aging, Clin Geriatr Med 1(1) 15–27 (1985)

7. L Hayflick, How and Why We Age, New York: Ballantine Books (1994)

8. L Hayflick, The future of ageing, Nature 408(6809) 267–269 (2000)

9. L Hayflick, “Antiaging” is an oxymoron, J Gerontol A Biol Sci Med Sci 59(6) B573–578 (2004)

10. J Campisi, Replicative senescence and old lives’ tale? Cell 84 497–500 (1996)

11. E Soudant, L Bezalel, M Ziv and I Perry, EU Patent No. 0973532; US Patent No. 6342254: Anti-proliferative Preparations

12. 1. D Harman, Aging: A theory based on free radical and radiation chemistry, J Gerontol 11(3) 298–300 (1956)

13. D Harman, Free radical theory of aging: Affect of free radical reaction inhibitors on the mortality rate of male LAF mice, J Gerontol 23(4) 476–482 (1968)

14. D Harman, The biologic clock: The mitochondria? J Am Geriatr Soc 20(4) 145–147 (1972)

15. D Harman, The aging process, Proc Natl Acad Sci USA 78(11) 7124–7128 (1981)

16. L von Oppen-Bezalel, Lightening, boosting and protecting with colorless carotenoids, Cosm & Toil 124(3) (Mar 2009)

17. L von Oppen-Bezalel, E Lerner, DG Kern, B Fuller, E Soudant, A Shaish, IBR-CLC, Colorless carotenoids: Phytoene and phytofluene from unicellular algae–applications in cosmetics, wellness and nutrition, Frag J, 34 3 48–53 (2006)

18. L von Oppen-Bezalel, Colorless carotenoids, phytoene and phytofluene for the skin: For prevention of aging/photo-aging from inside and out, SÖFW 7 (2007)

19. L von Oppen-Bezalel, UVA, A main concern in sun damage: Protection from the inside and outside with phytoene, phytofluene the colorless carotenoids and more, SÖFW 11 (2007)

20. BB Fuller, DR Smith, AJ Howerton and D Kern, Anti-inflammatory effects of CoQ10 and colorless carotenoids, J Cos Derm 5(1) 30–38 (2006)



Table 1. SPF of sunscreen creams with and without P&P

 Table 1. SPF of sunscreen creams with and without P&P


Figure 1. Effects of dormant and nondormant bulb extract

 Figure 1. Effects of dormant and nondormant bulb extract

Figure 2. Sensory analysis of dormins in a cosmetic cream

 Figure 2. Sensory analysis of dormins in a cosmetic cream

Figure 3. The colorless carotenoids phytoene and phytofluene absorption spectra

 Figure 3. The colorless carotenoids phytoene and phytofluene absorption spectra

von Oppen a dual approach footnotes

 a IBR-Dormin (INCI: Water (aqua) (and) Narcissus Tazetta Bulb Extract) is a product and registered trademark of IBR Ltd. 

b IBR Colorless Carotenoids (IBR CLC and TCLC) (INCI: Dunaliella Salina Extract; and INCI: Solanum Lycopersicum (Tomato) Fruit Extract, respectively) are products and registered trademarks of IBR Ltd. 

Formula 1. Antiaging and moisturizing o/w day cream

 Formula 1. Antiaging and moisturizing o/w day cream


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