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Topical Products for the Aging Face

Article  in  Clinics in plastic surgery · May 2016

DOI: 10.1016/j.cps.2016.03.005

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Top i c a l Pro d u c t s fo r t h e
A g i n g Fa c e
John P. McCook, BSc (Pharm), RPh

KEYWORDS
 Cosmeceuticals  Retinoids  Antioxidants  AHAs  PHAs  Anti-aging  Botanical extracts

KEY POINTS
 Facial topical treatment vehicles and product forms.
 Core antiaging cosmeceutical ingredients.
 Choosing topical cosmeceutical antiaging technologies.
 Combinations of topical cosmeceuticals.
 Clinical evaluation techniques for antiaging topical treatments.

INTRODUCTION patient toward the optimal home-use product

Each year there are scores of branded cosmetic
product lines and hundreds of new and existing
cosmetic products distributed through various
retail, Internet, direct sales, and professional or
physician-dispensed points of sale to the con-
suming public. The plastic surgeon and his or her
staff are well positioned between the companies
offering topical skin care products and the patients
seeking treatment for age-related facial issues. As
such, plastic and reconstructive surgeons and
aesthetic office staff are able to preview and
screen the plethora of available topical antiaging
products and technologies so as to recommend
the product or product treatment regimen that
best fits the particular needs of each patient. In do-
ing so, the professional staff has the opportunity to
augment in-office facial procedures by guiding the
regimen that addresses each patient’s particular
facial appearance–related concerns.
It is clear that topical treatment with cosme-
ceuticals can help improve facial aging issues
and extend the treatment effects of in-office treat-
ment procedures; in particular, improvements in
discreet or uneven pigmentation and overall skin
tone, surface roughness, fine and course rhytides,
diffuse redness, and blotchiness. Additionally,
sunscreens and antioxidants can add a level of
daily protection from reactive oxygen species to
help prevent further photodamage and dermal
malignancies.
The scope of this article is relatively narrow and
is focused mainly on nonprescription home-use
topical treatment technologies for the aging face.
The article is intended to serve as a guide to the
core cosmeceutical technologies currently used

Mr J.P. McCook is an independent consultant specializing in skin care product development and topical
plasticsurgery.theclinics.com

delivery systems for new pharmaceutical and cosmetic products. He has more than 45 years of cosmetic and
pharmaceutical product development experience with technical management positions in both the pharma-
ceutical and cosmetic industries as CEO and founder, Discovery Partners, LLC, COO and co-founder, Berg
Phama Division of Berg, LLC, Senior Vice President and CTO, Elizabeth Arden, Inc, and Vice President, R&D,
Mary Kay Cosmetics.
Conflict of Interest Statement: Mr J.P. McCook is a partner in CHL Industries, LLC, which licenses topical skin
care technology based on patented compositions containing sodium copper chlorophyllin complex. This
compound is mentioned in this article.
Discovery Partners, LLC, 4913 Southern Hills Drive, Frisco, TX 75034, USA
E-mail address: johnmccook@att.net

Clin Plastic Surg 43 (2016) 597–604

http://dx.doi.org/10.1016/j.cps.2016.03.005
0094-1298/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
598 McCook
and to help educate and assist the selection of
topical antiaging products by the professional
staff and their patients. References in cosmetic
dermatology are available that cover cosmeceuti-
cal technologies in much greater detail if there is
interest in a more intensive review of this
subject.1–3
PATIENT PROFILE AND TOPICAL
COSMECEUTICAL PRODUCT PERFORMANCE
Facial skin aging affects us all but significant
changes in facial surface topography begin in
middle age and are exacerbated with the accu-
mulation of UV damage from unprotected sun
exposure, smoking, and age-related hormonal
changes.4–6
Most patients seeking aesthetic facial treat-
ments are women and perimenopausal. However,
the cosmeceutical technologies described in this
article are not gender specific and are generally
appropriate for topical facial treatment of both
men and women. The terms “cosmeceutical”
and “antiaging” are used interchangeably in this
summary for the description of topical treatment
products, ingredients, or technologies for the
aging face.
The professional selections of home-use
topical cosmeceutical treatment products are
more likely to receive high patient satisfaction
ratings if the following product qualities are
achieved:
 Nonirritating
 Compatible with patient skin type (oily,
normal, dry, combination; Fitzpatrick type,
sensitive skin)
 Effective in the visible improvement in the
signs of facial skin aging specific to patient
needs in a reasonable time period
 Complementary to surgical and minimally
invasive office procedures
 Aesthetically elegant
First and foremost, cosmetic products should
be nonirritating for all skin types. A UK epidemi-
ologic study showed most women self-classify
their skin as “sensitive” with similarly high rates
in a survey of an ethnically diverse female popu-
lation in the United States.7 Test methods for
measuring facial skin sensitivity with lactic acid
solution or other probes have been studied but
may be somewhat impractical for screening pa-
tients in the office.8–10 Companies offering
cosmeceutical products typically evaluate the
final product formulation before sale in standard-
ized human patch tests (Human Repeat
Insult Patch Test [HRIPT]) to document that
each product is nonirritating and nonsensitiz-
ing.11 However, to further insure compatibility
of product formulations with a broad range
of the population, products may avoid
the inclusion of fragrance, formaldehyde-donor
preservatives, or other ingredients that can be
irritants or sensitizers to a small segment of the
population.
The patient’s Fitzpatrick scale skin type is of
course an important consideration regarding
susceptibility to UV damage and photoaging.
As skin ages, susceptibility to dryness
increases, mainly through loss of water-binding
ability of the stratum corneum, and regular use
of antiaging products that hydrate and help pro-
tect and reinforce the skin’s barrier properties
become more important.12 Patients who regularly
experience xerosis also may have areas of the
face that are normal or even oily, and these pa-
tients increasingly seek “oil-free” cosmetic
formulations.
Most patients are not novices in terms of
prior usage of topical antiaging products.
They will have developed a refined sense of
preferred product aesthetics. The visual
characteristics, ease of application, immediate
and longer term sensory qualities, and product
odor (or lack of odor) will be important consider-
ations for initial acceptance and continued pa-
tient use.
Daily use of the topical cosmeceutical prod-
ucts should show marked (visible) improvement
in the signs of aging, particularly those issues
of most concern to the patient. Patients expect
products to work quickly and some benefits,
such as softer and smoother skin, can occur in
minutes after a single application through
increased hydration of the stratum corneum.
However, changes in color and tone, skin tight-
ness and elasticity, and sustained reduction in
perioral and periorbital rhytides require one or
more complete turnover and restructuring of the
related facial epidermal and dermal tissue.
Daily use of antiaging topicals typically requires
treatment for several weeks or more for improve-
ments to be evident.
Last, the daily use of topical products for the
aging face can contribute significantly to
the global facial improvements of the minimally
invasive procedures discussed in the various
articles of this issue. For example, pro-
cedures that include energy-based devices or
chemical peels for the treatment of hyperpigmen-
tation can be augmented with daily use
of products containing a high level of broad-
spectrum sunscreen protection and use of topical
formulations with skin-lightening activity.13–15

TOPICAL COSMECEUTICAL TREATMENTS FOR
THE AGING FACE: CORE TECHNOLOGIES
The core cosmeceutical treatments for the aging
face are summarized under the following
headings:
 Topical cosmeceutical vehicles
 Topical antiaging cosmeceuticals
 Retinoids
 Antioxidants
 Alpha-Hydroxy Acids and Polyhydroxy
Acids
 Peptides and Biologicals
 Plant and Marine Extracts
 Product testing: clinical efficacy
TOPICAL COSMECEUTICAL VEHICLES
Topical facial antiaging treatment product forms
include lotions, creams, gels, and liquids. Lotion
and cream vehicles are thickened and homoge-
nized emulsions of lipids, water, and emulsifiers,
whereas gels, liquids, or “serums” are aqueous
vehicles containing water-soluble or water-
dispersible components to modify the thickness,
feel, pH, and skin penetration of the added bioac-
tive cosmeceuticals. The cosmeceutical also may
require the addition of skin penetrants, liposomal
complexes, polymer encapsulations, or other
skin-delivery mechanisms to achieve sufficient
penetration of the cosmeceutical active for clinical
efficacy.
Moisturizing Vehicles
The lipid and water-soluble components of the
topical treatment vehicle can have a positive
impact on the skin’s moisture barrier and water
content by helping to moisturize and protect the
face.
Although cosmetic moisturizers are not gener-
ally thought of as cosmeceutical treatments, facial
moisturizers represent a major category of recom-
mended daily-use topicals.16 Regular use of a
facial moisturizer can soften and smooth the stra-
tum corneum and prevent dry patches and associ-
ated tightness, itching, and irritation through active
hydration and by reduction of skin transepidermal
water loss.
The primary purpose of the facial moisturizer is
to maintain skin hydration, typically through the
application of a cream or lotion vehicle that con-
tains additives that may include the following:
 Skin barrier lipids
 Ceramides
 Cholesterol
 Fatty acids
Topical Treatments for the Aging Face 599
 Water-binding humectants
 Glycerin and other short-chain glycols
 Sodium hyaluronate
 Pyrrolidone carboxylic acid and other
amino acids
 Proteins
 Lactate, urea, and other salts
 Sugar derivatives
 Protectants
 Natural and synthetic polymers
 Waxes, vegetable and mineral oils,
petrolatum
Moisturizing product formulations in the form of
creams, lotions, gels, and serums are often the
base vehicle for inclusion of a retinoid, antioxidant,
peptide, botanical or marine extract, or other anti-
aging cosmeceutical that is described in the
following section.
ANTIAGING TOPICAL COSMECEUTICALS
Topical antiaging active ingredients fall into several
classes, defined by chemical structure (retinoids,
alpha-hydroxy acids [AHAs], polyhydroxy acids
[PHAs], vitamins [C, E, B3, B5], peptides, and
proteins), by source (botanical extracts, marine
extracts), and by function (eg, antioxidants, growth
factors, skin lighteners, humectants, barrier lipids,
anti-irritants, anti-inflammatories) There is, of
course, considerable overlap in the characteriza-
tions. For example, many botanical extracts func-
tion as antioxidants and some antioxidants have
other functional properties that may include skin
lightening, anti-redness, wrinkle reduction, or other
properties when applied topically at certain con-
centrations. The major categories of antiaging cos-
meceuticals are listed in Table 1.
Retinoids
Topical retinoid treatment is still the primary refer-
ence standard for clinically effective topical anti-
aging products.
It has been more than 30 years since Kligman
and colleagues17 reported the ability of topically
applied all-trans retinoic acid to repair the UV-
damaged dermis. Today, retinoic acid is still
considered the gold standard of clinical efficacy
for the topical treatment of facial rhytides. Topical
retinoids, the collective term for retinoic acid and
other vitamin A compounds that also includes
retinaldehyde, retinol, and various retinyl esters,
have all been shown to be clinically effective
when used topically.18–20
Retinoic acid is the most effective of the
topical retinoids and is typically used at 0.025%
to 0.05% in a topical cream base (Renova Cream
600 McCook

Table 1
Topical antiaging cosmeceuticals

Chemical Class or Type Examples

Vitamins Vitamin A retinoids (all-trans retinoic acid, retinaldehyde, retinol,
retinyl esters), vitamin E tocopherols and tocotrienols, vitamin C
(ascorbic acid, various water-soluble and lipid-soluble ascorbates),
vitamin B3 (niacinamide), vitamin B5 (panthenol).
Antioxidantsa Ascorbic acid and ascorbates, alpha lipoic acid, tocopherol and
tocotrienols, kojic acid, ferulic acid, resveratrol, glutathione,
ergothionine, sodium copper chlorophyllin complex, quercetin,
glycyrrhizin and glycyrrhizinate salts.
Plant and marine extractsb Tea polyphenols; yeast and oat beta glucans; red and brown algae
extracts, Centella asiatica extract; soy isoflavones; grape extracts;
Echinacea sp. extracts; licorice extracts.
Hydroxy acids (alpha-hydroxy Glycolic, lactic, citric, mandelic, and hydroxypropionic acids; salicylic
acids, beta-hydroxy acids, acid; gluconolactone and lactobionic acid.
and polyhydroxy acids)
Peptides and biologicals Dipalmitoyl hydroxyproline; palmitoyl dipeptide-5; palmitoyl
hexapeptide-12; palmitoyl tripeptide-5; copper tripeptide, kinetin;
extracts of growth factors (vascular endothelial growth factor,
epidermal growth factor, transforming growth factor-beta).
a
Antioxidants also may be vitamins (eg, vitamin A, E, and C) or derived from nature (plant or marine extracts).
b
This is a limited list of more common extracts. There are several hundred different plant-based cosmeceutical extracts
commercially available that claim antioxidant activity.

[Ortho-Neutrogena] and Retinoic Acid [tretinoin] Cosmetic or over-the-counter retinoid for-

Cream, USP). Clinical improvement of photoaged
skin with tretinoin or other prescription retinoids
(eg, tarazotene, adapalene, isotrentinoin) has
been reported with several published clinical
trials.21 However, topical retinoic acid can be
irritating to a significant percentage of the popula-
tion. Retinol, which metabolizes to retinaldehyde
and retinoic acid, has been found to be less irri-
tating than retinoic acid but must be used at a
higher concentration. Topical antiaging treatment
products containing retinol have become in-
creasingly popular in the past decade and
may include retinol-polymer delivery systems
that improve the stability and shelf life of the retinol
products and help to further reduce irritation
potential by slowing the rate of epidermal
penetration.22–24
Because topical retinoid use can compact and
thin the epidermal layer, patients should be
cautioned to always use a broad-spectrum sun-
block (UVA & UVB; minimum SPF30) during the day.
Patients who may be sensitive to topical over-
the-counter retinol usually show sensitivity during
the first week of usage. In patients with sensitive
skin, the sensitivity may be attenuated by first
titrating the usage frequency or retinol concentra-
tion, or both, from lower to higher, during the first
few weeks of treatment.25
mulations usually contain one or more other cos-
meceutical ingredient (see Table 1) that is
designed to complement the improvements in
skin texture, tone, and rhytides produced by
retinol. Other cosmeceuticals combined directly
with retinol must, however, be compatible for the
long-term stability of both retinol and the addi-
tional cosmeceutical.
For patients who cannot tolerate topical retinol,
many retinol-free antiaging formulations exist that
may contain one or more nonretinoid cosmeceut-
icals listed in Table 1.
Antioxidants
Antioxidant compounds have emerged as the
most frequently used cosmeceutical ingredients
in topical antiaging treatment products to date.
At low concentrations (10–1000 ppm), cosmetic
antioxidants may be included to prevent oxidative
deterioration of other cosmeceuticals and the
inactive cosmetic vehicle ingredients that can be
sensitive to oxidation.
However, at higher concentrations, the cosmetic
antioxidants can produce clinically relevant im-
provements in photodamaged facial skin.26,27
Antiaging topical products may include one or
more of the antioxidant compounds listed in

Table 1, as well as one or more of the many bota-
nic extracts that contain antioxidant flavonoid
compounds.28–31
Vitamin C (L-ascorbic acid) has been used as a
primary antiaging topical treatment for several
decades. Topical formulations containing 5% or
more of L-ascorbic acid have been shown to be
clinically effective antiaging treatments.32–34
Water-soluble vitamin C salts (eg, sodium
ascorbate, magnesium ascorbyl phosphate,
ascorbyl glucoside) and lipid-soluble vitamin C
derivatives (eg, tetrahexyldecyl ascorbate,
ascorbyl palmitate, dipalmitoyl ascorbate) may
be added to topical retinol formulations to
supplement retinol efficacy, particularly in the
improvement of skin tone. Formulations contain-
ing L-ascorbic acid also have been used to reduce
CO2 laser resurfacing erythema.35
Sodium copper chlorophyllin complex, an
antioxidant compound previously used in topical
wound-healing ointments, has recently been
evaluated as an antiaging treatment for photo-
aged skin and found to have anti-inflammatory,
skin-lightening, and antihyaluronidase activity
when applied topically in a liposomal delivery
system.36 The facial antiaging activity of this
compound appears to derive from both the
strong antioxidant activity and the antihyaluro-
nidase activity of this molecule and certain
analog compounds contained within the
complex.37,38
Alpha-Hydroxy Acids and Polyhydroxy Acids
The clinical relevance of AHAs for the treatment of
photoaged skin was first established by Van Scott
and Yu39,40 more than 3 decades ago.
Daily applications of glycolic or lactic acid in
concentrations of 5% to 15% exfoliate surface
layers, compact the epidermis, and stimulate the
production of glycosoaminoglycans and collagen.
Higher concentrations of glycolic and lactic
acids and other acids are used as chemical peels
in office procedures for rejuvenation of photoaged
skin.41 However, potential for stinging, burning,
and redness can preclude even daily use of AHA
topicals on patients with sensitive skin.
For daily use, antiaging facial treatments, PHAs
(eg, gluconolactone, lactobionic acid) may be
better tolerated and offer potentially broader
antiaging effects over AHAs. Lactobionic acid is
functionally similar to AHAs in terms of enhanced
cell turnover activity but it is also a strong
humectant, a chelator, an inhibitor of matrix
metalloproteinases, and an antioxidant that
inhibits lipid peroxidation.42–44
Topical Treatments for the Aging Face 601
Peptides and Biologicals
Antiaging peptide compounds (see Table 1) have
been shown to upregulate collagen production
(in vitro) and have shown clinical improvements
when applied topically to photodamaged
skin.45,46 Peptides also have been formulated
and evaluated in combination with retinoids
in vivo and show repair of photodamaged skin.47
Cell culture extracts containing natural enzymes
or growth factors are also offered by cosmeceuti-
cal manufacturers as antiaging treatments.
Growth factor proteins present in the skin such
as epidermal growth factor, fibroblast growth
factor, platelet-derived growth factor, and others,
or mixtures of several growth factors produced in
cell culture, have been shown to improve periorbi-
tal and perioral wrinkles, roughness, and mottled
pigmentation when clinically tested in topical
formulations.48–50
Plant and Marine Extracts
There are several hundred botanical extracts from
various plant parts (eg, seeds, stem, bark, fruit)
and marine extracts (eg, extracts of red or brown
algae) offered as topical antiaging cosmeceuti-
cals.2 Many of these extracts claim antioxidant or
broader antiaging activity based on in vitro testing,
but few of the extracts from natural sources have
validated the antiaging efficacy based on well-
controlled clinical studies.29,51,52 Without any
standardization for potency of the extract or
evaluation of clinical or in vivo biological activity
against a known reference standard such as reti-
noic acid, it is difficult to measure the contribution
of any particular extract to the overall topical prod-
uct performance.
PRODUCT TESTING: CLINICAL EFFICACY
With hundreds of antiaging cosmeceuticals
available, and many newly introduced each year,
choosing which topical antiaging product or
product regimen will perform best against each
patient’s needs is a daunting task.
The best predictor of product efficacy is clinical
evaluation of the commercial formulation over the
course of several weeks or months. The evaluation
should include a statistically relevant number of
subjects, carefully screened and selected to
meet the facial aging parameters of interest, with
appropriate controls.
Clinical studies of new topical products for the
aging face will typically include clinical grading
scales and photographic and instrumental mea-
surements and methods.53–55
602 McCook
Fig. 1. (A, B) Silicone replicas. (A) Baseline. (B) After 8 weeks of treatment. (Courtesy of Stephens & Associates,
Richardson, TX.)
Clinical grading assesses global facial improve-
ment and improvements in individual signs of
facial aging, for example
 Periorbital and perioral rhytides
 Tactile and visual roughness
 Visual and instrumentally measured dryness
 Discreet hyperpigmentation and dyschromia
 Diffuse redness, inflammation
 Skin laxity
Clinician and photographic grading can be
supplemented with various objective techniques.
For example, changes in silicone replicas of
periorbital rhytides are an accurate way to docu-
ment changes from baseline through study end,
as seen in Fig. 1 (baseline and after 8 weeks of
treatment). Improvement in epidermal elastosis
can be quantified by ultrasound. Sonographs of
before and after treatment (Fig. 2) show decreased
elastosis (dark regions) and improvement in skin
density (light pixels).
Fig. 2. (A, B) Ultrasound imaging. (A) Baseline (density 5 28). (B) After 8 weeks of treatment (density 5 32).
(Courtesy of Stephens & Associates, Richardson, TX.)
SUMMARY/DISCUSSION
There are scores of topical antiaging products
offered to the professional market. The surgeon
and aesthetic staff are faced with the daunting
task of choosing which topical antiaging product
or product line is best suited for their patients to
complement in-office procedures.
Daily broad-spectrum UV protection and combi-
nations of a topical retinoid with antioxidants and
other compatible topical bioactive agents would
seem to be a logical strategy to supplement
in-office procedures so as to maximize the treat-
ment regimen for the aging face. However, patient
facial skin sensitivity, history of topical antiaging
product use, and specific patient facial aging con-
cerns should be first considered in selecting a
home-use treatment regimen that is designed to
best fit individual patient needs.
The cosmetic industry is relatively fast-paced
and creative and new cosmeceutical antiaging

technologies and ingredients are introduced every
year. New topical bioactive ingredients, formu-
lated as monotherapy or in combination with
well-known and accepted cosmeceuticals, such
as retinoids, AHAs, peptides, and ascorbates,
should be supported with a clinical performance
portfolio and published studies in relevant derma-
tology journals.
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