Original Contribution

Blackwell Publishing
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INAL CONTRIBUTION

The latest cosmeceutical approaches for anti-aging

Zoe Diana Draelos, MD
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC

Summary Background Cosmeceuticals provide a new therapeutic frontier for anti-aging in derma-
tology. The most dramatic signs of cutaneous aging include the lack of skin surface regu-
larity, the formation of rhagades, and the increased presence of dyspigmentation.
Background The objective of this review is to illustrate how these three needs of maturing
skin can be met by novel ingredients incorporated into carefully constructed formula-
tions designed to deliver scientifically measurable and visibly noticeable improvement.
Conclusion Skin surface irregularity can be improved through increased skin turnover
facilitated by topical niacinamide, while the appearance of fine lines can be diminished
through the application of moisturizers containing engineered peptides and over-the-
counter retinoids, such as retinyl propionate. Finally, skin pigmentation can become
more regular with the topical application of N-acetyl glucosamine and ultraviolet A
photoprotective ingredients. Furthermore, combining cosmeceutical ingredients in a
moisturizing vehicle can magnify benefits and profoundly improve skin appearance.
Keywords: cosmetics, skin aging, skin physiology

fibers and loss of subcutaneous fat yielding facial fine

Introduction
Cosmeceuticals provide an evidence-based approach to
the treatment of aging skin. Aging skin is typically
characterized by the lack of skin surface regularity, the
formation of rhagades, and the increased presence of
dyspigmentation. The skin surface is regularly irregular
in youth with dermatoglyphics created by the cutaneous
peaks around the hair and the follicular ostia and
intervening valleys. With aging, the increase in sebaceous
gland size, growth of benign neoplasms (seborrheic
keratoses, adenexal tumors, etc.), and appearance of
clumped elastin yield a skin surface that is irregularly
irregular. This irregularity is increased by the presence of
inefficiently desquamating corneocytes. Further skin
aging is characterized by the breakdown of collagen
lines and wrinkles. These changes are related to effects of
ultraviolet (UV) radiation on dermal collagen; however,
UV can also damage melanocytes, causing selective
clones to overproduce melanin. This localized melanin
overproduction yields dyspigmentation. Thus, aging skin
can be characterized by poor texture, wrinkling, and
irregular pigmentation.
Discussion
A variety of cosmeceuticals exist that can improve the
appearance of skin by effects on skin texture, wrinkling,
and dyspigmentation. The scientific validation to document
ingredient efficacy in each of these areas of skin aging is
discussed below.

Skin texture

Correspondence: Zoe Diana Draelos, MD, 2444 North Main Street, High The inevitable growth of benign neoplasms on the skin
Point, NC 27262. E-mail: zdraelos@northstate.net surface cannot be eliminated with current cosmeceutical

2 © 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 2–6


Figure 1 Topical niacinamide improves skin surface texture.
technology, but removal of improperly desquamating
corneocytes can improve the appearance of skin. Alpha
hydroxy acids (AHA), such as glycolic and lactic acids,
were the first cosmeceuticals to improve cutaneous
exfoliation through chemical dissolution of the intercor-
neocyte bonds. While these agents increased desquamation,
they also increased irritation due to rapid penetration of
the dermis by the low pH AHA. Newer cosmeceutical
approaches to improving skin texture use ingredients
such as niacinamide that improve rather than degrade
barrier function.
Niacinamide, the amide form of vitamin B3, is a deriv-
ative of niacin. Niacin is a precursor to a family of enzyme
cofactors, such as nicotinamide adenine dinucleotide
(NAD), its phosphorylated derivative (NADP), and their
reduced forms (NADH, NADPH), which regulate cellular
metabolism and cell renewal. The diversity of processes in
which these cofactors participate may be the mechanistic
basis for the variety of cosmetic benefits observed from
the topical use of niacinamide.1 Improvement in skin tex-
ture from the topical use of niacinamide (Fig. 1) has been
attributed to enhanced barrier function in normal subjects2
and in subjects with rosacea who have sensitive skin.3
Figure 2 Topical pal-KTTKS improves the
appearance of facial skin wrinkles after
12 weeks of use.
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 2– 6
Latest cosmeceuticals for anti-aging • Z D Draelos
Wrinkling
Enhanced barrier function can also contribute to
improvement in skin wrinkling. The most common and
reversible cause of fine skin wrinkling is dehydration.
When the barrier function is optimal, skin hydration is
maintained by the prevention of transepidermal water
loss (TEWL). Peptides, such as palmitoyl-lysine-threonine-
threonine-lysine-serine (pal-KTTKS), can improve barrier
function when applied to the skin in a moisturizing base.
KTTKS, a fragment of human dermal collagen I, has been
studied for its ability to speed wound healing by stimulating
new collagen production.4 Synthetic pal-KTTKS also
stimulates collagen production in vitro and reduces the
appearance of fine lines and wrinkles in photoaged facial
skin shown in a randomized, double-blind clinical study
utilizing topical pal-KTTKS applied twice daily for
12 weeks (Fig. 2).5,6
In addition to reducing the wrinkles of dehydration,
cosmeceuticals can improve skin wrinkling by increasing
dermal thickness. This effect is accomplished through
the topical application of retinoids, such as retinoic acid,
which interact with nuclear receptor proteins to affect
transcription, resulting in either increased or decreased
expression of specific proteins and enzymes. Retinoids
produce increased epidermal proliferation, increased
epidermal ground substance, and increased production
of extracellular dermal collagen, all of which result in
thicker skin and fewer visible wrinkles.7
Although trans-retinoic acid is a pharmaceutical product,
the retinoid family includes other compounds, including
retinaldehyde, retinol, and retinyl esters such as retinyl
propionate, which are available as cosmeceutical ingredi-
ents. Retinaldehyde is the most irritating of the three, fol-
lowed by retinol and retinyl propionate.8,9 Concentrations
less than 1% are typically less irritating than higher
3
Latest cosmeceuticals for anti-aging • Z D Draelos
Figure 3 Retinyl propionate (RP) and retinol (ROH) produced a
reduction in wrinkling and hyperpigmentation compared to
baseline after 12 weeks of use as reported by expert graders (0–4
scale).
concentrations and still effective in appearance improvement.
In a 12-week, double-blind, split-face, placebo-controlled
clinical study, retinol (0.15%) and retinyl propionate (0.30%)
were effective in reducing the appearance of facial wrin-
kles (Fig. 3).10
Dyspigmentation
The last area of interest for discussion of the aging face is
dyspigmentation. While wrinkling is the most significant
sign of photoaging for patients with Fitzpatrick skin types
I to III, dyspigmentation is the major concern for patients
with darker skin types. The elimination of hydroquinone
from the over-the-counter market in the United States,
4 © 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 2–6
Europe, and Japan has created a need for other cosmeceutical
ingredients capable of evening skin color.
N-acetyl glucosamine, an amino-monosaccharide pro-
duced by the body through the addition of an amino
group to glucose, is the newest cosmeceutical ingredient
to improve skin color.11 It has many roles within the body
including as a substrate for the production of hyaluronic
acid, heparan sulfate, and proteoglycans. These sub-
stances serve as humectants and are important in
maintaining the water content of the dermis. N-acetyl
glucosamine also inhibits the glycolsylation of tyrosi-
nase, an important enzyme in melanin production.12,13
Its ability to improve facial dyspigmentation was shown
in a randomized, double-blind clinical study utilizing
topical 2% N-acetyl glucosamine applied twice daily for
8 weeks (Fig. 4).14
Facial dyspigmentation can also be improved with cos-
meceutical ingredients that prevent both UVA and UVB
radiation from striking the skin. UV radiation is primarily
responsible for the dyspigmentation associated with pho-
toaging. The UVA filters that are most effective in cos-
meceutical formulations include octocrylene, oxybenzone,
avobenzone, ecamsule, and zinc oxide. Octocrylene is a
thick oil that provides UVB and weak UVA photoprotec-
tion and may also be used to photostabilize avobenzone,
prolonging its ability to absorb UVA radiation. Oxyben-
zone, avobenzone, octocrylene, and ecamsule are organic
UVA filters, which undergo a chemical reaction to provide
photoprotection, while zinc oxide is an inorganic broad-
spectrum UVA and UVB filter. Zinc oxide absorbs and
Figure 4 Improvement in facial
pigmentation following 8-week topical
application of N-acetyl glucosamine.

reflects (scatters) UV radiation and is extremely photostable.
The photoprotective abilities of zinc oxide can be increased
by coating the particles with silicone, creating a filter that
can prevent the formation of both primary and secondary
oxygen radicals. The aesthetics of zinc oxide have been
optimized by using microfine particles that do not appear
white when placed on the skin surface. Photoprotection
is an important consideration for the treatment of facial
dyspigmentation.
Combining cosmeceutical ingredients
Combining cosmeceuticals with different mechanisms of
action in an optimized moisturizing vehicle can increase
the magnitude of skin anti-aging benefits. For example,
combining niacinamide with pal-KTTKS (Fig. 5a) or
Figure 5 (a) Topical application of niacinamide in combination
with pal-KTTKS increases the wrinkle reduction effect. (b) Topical
application of N-acetyl glucosamine (NAG) in combination with
niacinamide in Caucasian subjects increases the spot reduction
effect.
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 2– 6
Latest cosmeceuticals for anti-aging • Z D Draelos
N-acetyl glucosamine (Fig. 5b) increases the skin appearance
benefit.10,14
Summary
The three major areas for appearance improvement in
photoaged skin are texture, wrinkling, and dyspigmentation.
Evidence-based cosmeceutical ingredients can provide
these anti-aging benefits. The best results are achieved by
carefully combining compatible ingredients in an optimized
moisturizing vehicle to create a multifunctional product.
The vehicle must be constructed to provide the immediate
benefits of preventing TEWL by occlusion and enhancing
humectancy while creating a smooth tactile surface.
These conditions are conducive to barrier repair, which
can be enhanced by niacinamide and synthetic peptides.
Other ingredients, such as retinoids and N-acetylglucosamine,
can be added to provide the long-term benefits of increased
skin thickness and improved dyspigmentation. Finally,
UVA photoprotection can be provided with oxybenzone,
avobenzone, ecamsule, or zinc oxide to prevent further
signs of aging. This new generation of efficacious cosme-
ceuticals can provide valuable skin benefits.
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