International Journal of Cosmetic Science, 2008, 30, 323–332
Review Article
A review of ageing and an examination of clinical
methods in the assessment of ageing skin. Part 2:
Clinical perspectives and clinical methods in the
evaluation of ageing skin
T. M. Callaghan1 and K.-P. Wilhelm
proDERM Institute for Applied Dermatological Research, Kiebitzweg 2, 22869 Schenefeld/Hamburg, Germany
Received 8 February 2008, Accepted 21 April 2008
Keywords: clinical assessment of ageing skin, non-invasive skin methods, skin efficacy testing
Synopsis
With the advancement of skin research, today’s
consumer has increased access to technological
information about ageing skin and hair care prod-
ucts. As a result, there is a rapidly increasing
demand for proof of efficacy of these products. Rec-
ognizing these demands has led to the develop-
ment and validation of many clinical methods to
measure and quantify ageing skin and the effects
of anti-ageing treatments. Many of the current
testing methods used to research and evaluate
anti-ageing product claim to employ sophisticated
instruments alongside more traditional clinical
methods. Intelligent use of combined clinical meth-
ods has enabled the development of technologi-
cally advanced consumer products providing
enhanced efficacy and performance. Of non-inva-
sive methods for the assessment and quantification
of ageing skin, there is a plethora of tools available
to the clinical researcher as defined by key clini-
cally observed ageing parameters: skin roughness
Correspondence: K.-P. Wilhelm, proDERM Institute for
Applied Dermatological Research, Kiebitzweg 2, 22869
Schenefeld/Hamburg, Germany. Tel.: +49 40 839
358 11/+49 40 839 358 17; fax: +49 40 839 358 39;
e-mail: sleuschner@proderm.de
1
Authors present address: DermPharCos, Witts Park 16,
22587 Hamburg, Germany.
ª 2008 proDERM GmbH. Journal compilation
ª 2008 Society of Cosmetic Scientists and the Société Française de Cosmétologie
and surface texture; fine lines and wrinkles; skin
pigmentation; skin colour; firmness and elasticity;
hair loss; and proliferative lesions. Furthermore,
many clinical procedures for the evaluation of age-
ing skin treatments are combined with invasive
procedures, which enable added-value to claims
(such as identification and alteration of biochemi-
cal markers), particularly in those cases where
perception of product effect needs additional sup-
port. As discussed herein, clinical methods used in
the assessment of skin ageing are many and
require a disciplined approach to their use in such
investigations.
Résumé
Avec les progrès des recherches sur la peau, les con-
sommateurs aujourd’hui ont un accès accru
aux informations technologiques concernant le
vieillissement de la peau et les produits de soins
capillaires. Il en découle une demande rapidement
croissante des preuves d’efficacité de ces produits.
La reconnaissance de ces demandes a conduit au
développement et à la validation de nombreuses
méthodes cliniques pour mesurer et quantifier la
peau âgée ou le vieillissement de la peau et les effets
des traitements anti-âge. Beaucoup des méthodes
de test classiques utilisées pour rechercher et éva-
luer les revendications des produits antivieillisse-
ment reposent sur des instruments sophistiqués, à
323
Clinical perspectives and clinical methods in the evaluation of ageing skin T. M. Callaghan and K.-P. Wilhelm

côté des méthodes cliniques plus tradition- • hair loss

nelles. La combinaison intelligente de méthodes
cliniques a permis le développement de produits
commerciaux aux technologies avancées, possédant
une efficacité et une performance améliorées. A par-
tir de méthodes non invasives pour la détermina-
tion et la quantification des peaux âgées, une
pléthore d’outils utilisables par les chercheurs
cliniciens a été développée. Elle repose sur les para-
mètres cliniques-clés observés lors du vieillisse-
ment : rêcheur de la peau et texture de surface,
ridules et rides, pigmentation de la peau, couleur de
la peau, fermeté et élasticité, chute des cheveux et
lésions proliférantes. De plus, de nombreuses pro-
cédures cliniques pour l’évaluation des traitements
des peaux âgées sont combinées à des procédures
invasives qui permettent des revendications à
valeur ajoutée comme l’identification et l’altération
de marqueurs biochimiques, en particulier dans les
cas où la perception de l’effet du produit nécessite
une argumentation complémentaire. Comme dis-
cuté ici, les méthodes cliniques utilisées pour la
détermination du vieillissement de la peau sont
nombreuses et nécessitent une approche contrôlée
pour pouvoir les utiliser dans de telles recherches.
• unwanted hair
• nail plate thins, development of ridges
Visual comparison of chronologically sun-
exposed vs. sun-protected skin reveals that age-
associated alterations in the skin’s appearance are
a result of sun exposure. Ageing is accelerated in
those areas exposed to sunlight (ultraviolet radia-
tion), a process known as photoageing. Photo-
ageing is because of a combination of short
wavelength (UVB) injury to the outer layers of the
skin (epidermis) and long wavelength (UVA) injury
to the middle layers (dermis). Photoaged skin
appears wrinkled, flaccid, rough with uneven pig-
mentation, etc. (Fig. 1) with an increased epider-
mal thickness and alterations of connective tissue
organization. The key feature of photoaged skin is
the accumulation of amorphous elastin-containing
material that resides beneath the epidermal–dermal
junction. Impairment of collagen and elastin orga-
nization is typically more severe in photoaged skin

Introduction

As the body ages, the appearance and characteris-

tics of the skin alter. Chronologically aged skin is
thin, relatively flattened, dry and unblemished
with some loss of elasticity and age-related loss of
architectural regularity. It shows a general atro-
phy of the extracellular matrix, which is reflected
by a decrease in the number of fibroblasts.
Furthermore, there are reduced levels of collagen
and elastin and their organization is impaired.
This is because of decreased protein synthesis
affecting types I and III collagen in the dermis
with an increased breakdown of extracellular
matrix proteins [1, 2].
The common signs of intrinsic ageing are:
• fine wrinkles
• thin and transparent skin
• loss of underlying fat leading to hollowed cheeks
and eye sockets with noticeable loss of firmness
on the hands and neck
• bones shrink away from the skin as a result of Figure 1 Characteristic features of photoaged skin. Note
bone loss, which causes sagging skin wrinkling in the orbital and periorbital regions of the
• dry skin with pruritis face, skin laxity, uneven pigmentation and coarse skin
• inability to sweat sufficiently to cool the skin texture. Telangiectases are apparent in the naso-labial
• greying hair eventually turning white folds.

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324 International Journal of Cosmetic Science, 30, 323–332
Clinical perspectives and clinical methods in the evaluation of ageing skin T. M. Callaghan and K.-P. Wilhelm

(a) compared with chronologically aged skin (Fig. 2).

The severity of photoageing is proportional to accu-
mulated sun exposure and inversely related to
degree of skin pigmentation. Individuals with fair
skin are more susceptible to solar UV-induced skin
damage than darker-skinned individuals.
Photoaged skin is classified according to the Glo-
gau [3] score and the degree of wrinkling observed
as:
• Mild (age 28–35 years): few wrinkles, no kera-
toses (Fig. 3a).
• Moderate (age 35–50 years): early wrinkling,
sallow complexion with early actinic keratoses
(Fig. 3b).
• Advanced (age 50–60 years): persistent wrin-
kling, discolouration of the skin with telangiec-
tases and actinic keratoses (Fig. 3c).
• Severe (age 65–70 years): severe wrinkling,
(b)
photoageing, gravitational and dynamic forces
affecting the skin, actinic keratoses with or with-
out skin cancer (Fig. 3d).

Clinical aspects of ageing skin

With the advancement of skin research, today’s
consumer has increased access to technological
information about skin care products. As a result,
the demand for proof of efficacy especially for anti-
ageing products is rapidly increasing. Recognizing
these demands has led to the development and
validation of many clinical methods to measure
and quantify ageing skin and the effects of anti-
ageing treatments.
Of non-invasive methods for the assessment and
quantification of ageing skin, there is a plethora of
(c) tools available to the clinical researcher as defined
by key clinically observed ageing parameters:
• skin roughness and surface texture
• fine lines and wrinkles
• skin pigmentation
• skin colour
• firmness and elasticity
• hair loss
• proliferative lesions

Figure 2 Impairment of collagen organization in the

photodamaged skin. In Vivo confocal microscope images
of superficial reticular dermis in (a) 41-year-old female,
(b) 57-year-old male and (c) 75-year-old male. Note com-
paction of collagen fibres with increasing age (with per-
mission: Lucid Inc., Rochester, NY, U.S.A.).

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International Journal of Cosmetic Science, 30, 323–332 325
Clinical perspectives and clinical methods in the evaluation of ageing skin T. M. Callaghan and K.-P. Wilhelm

(a) (b) (c) (d)

Figure 3 Glogau scores for the photoaged skin: (a) few wrinkles, no keratoses; (b) early wrinkling (c) persistent wrin-
kling and skin discoloration; (d) severe wrinkling, photodamage and sagging.

Skin roughness and surface texture

(a)
As the skin ages, changes in the texture (topogra-
phy) and roughness or smoothness of the skin are
apparent as a result of loss of barrier integrity and
therefore resulting in increased water loss, as well
as changes in the collagen-supporting matrices
showing visibly on the skin surface.
Changes in skin barrier integrity can be mea-
sured using transepidermal water loss (TEWL), a
measure of cutaneous barrier function reflecting
the skin water content. It is defined as the mea-
surement of the quantity of water that passes
through the epidermis to the surrounding atmo-
(b)
sphere via diffusion and evaporation processes.
The autonomic nervous system, body temperature
and blood flow to the skin control the amount of
TEWL. Despite anatomical differences in TEWL
measurements, barrier function does not appear to
decrease with age and this can be seen in overall
decreased TEWL measurements [4–6].
Corneometry, which measures electrical capaci-
tance of the skin, gives an indication of how much
the skin is actually hydrated. This measurement is
also strongly influenced by the activity of the
sweat glands.
d-Squames and corneosurfometry are useful reli-
able standardized techniques for providing infor-
mation on the dryness and therefore roughness of
the skin surface (Fig. 4a,b).
In vivo confocal Raman spectroscopy is a sophisti-
Figure 4 Dry skin of lower leg (a) and examples of
cated technique, which provides actual quantita- d-squame sampling illustrating surface roughness
tive measurements of the amount of water (and (dryness) of the skin (b).
other molecules) in the skin. The method relies on
inelastic scattering or Raman scattering of mono- microns in diameter, the resulting photon flux is
chromatic light. Raman confocal microscopy has a much higher than achieved in conventional
very high spatial resolution. As the objective lenses Raman set-ups. This has the added benefit of
of microscopes focuses the laser beam to several enhanced fluorescence quenching. By using

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326 International Journal of Cosmetic Science, 30, 323–332
Clinical perspectives and clinical methods in the evaluation of ageing skin
Figure 5 Surface topography of ageing skin as seen by
videomicroscopy.
Raman microspectroscopy, in vivo time- and space-
resolved Raman spectra of microscopic regions of
samples can be measured.
As the skin ages, the surface topography of the
skin also changes (Fig. 5). Videomicroscopy is a
non-contact method, which can show age-related
changes in the surface of the skin. Image analysis
provides quantification of data obtained.
Figure 6 PRIMOS imaging of the
skin surface: periorbital region.
Figure 7 DermaTOP imaging of
periorbital region of the face high-
lighting skin furrows.
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International Journal of Cosmetic Science, 30, 323–332
T. M. Callaghan and K.-P. Wilhelm
Another non-contact method for evaluating
changes in skin surface profiles is Fringe Projec-
tion, a method in which phase-shifted fringe pat-
terns are created by a micro-mirror device and
then projected to the skin by a computer-con-
trolled digital projection system. Three shifted
fringe images are captured by a digital camera
positioned at an angle different from that of the
projection system. These three images are used
to retrieve the 3-D surface contour of the skin
(Figs 6 and 7). There are currently two main
types of systems commercially available each
very similar in their approach – PRIMOS (Pri-
mos, Teltow, Germany) and DermaTOP (Breuck-
Mann GmbH, Meersburg, Germany). The main
difference between them is how the fringe pat-
terns are generated. PRIMOS uses micro-mirrors
and requires a different system for each field
size/type, whereas DermaTOP uses a template for
shadows onto the skin and also offers the option
of different field sizes within one system. Fringe
Projection is particularly useful for measuring
changes in wrinkle depth (see section Fine lines
and wrinkles).
327
Clinical perspectives and clinical methods in the evaluation of ageing skin T. M. Callaghan and K.-P. Wilhelm

SkinChip technology is a relatively new skin

imaging technique [7, 8], which enables the skin II 4–6 Fine to moderate
depth wrinkles,
surface to be imaged according to its capacitance.
moderate number
Consequently, the images generated provide a pre- of wrinkles
cise observation of the skin topography that can III 7–9 Fine to deep wrinkles,
be easily quantified in terms of line density and numerous lines, with
line orientation. The mean grey levels of the or without redundant
skin folds
images closely correlate to Corneometer values.
This method is a very convenient way for charac-
terizing the properties of the skin surface.
Moderate (distinct
elastosis, with yellow
translucency under
direct light)
Severe [multipapular
and confluent elastosis
(thickened yellow and
pallid) approaching or
consistent with cutis
rhomboidalis]

Wrinkles can be measured using the Fringe Pro-

Fine lines and wrinkles
The skin surface topography is a polygonal mic-
rorelief with furrows and wrinkles representing the
three-dimensional organization of the epidermis,
dermis and the subcutaneous tissue. It depends on
morphological characteristics like thickness of the
cornified layer and collagen content, and it may
be considered as a mirror of the functional status
of the skin. The quantitative determination of the
skin’s surface topology, both skin roughness and
macrostructures, such as wrinkles and cellulite is
one of the most important and frequently per-
formed non-invasive clinical investigations. The
skin’s microrelief will alter progressively with age
including the appearance of wrinkles. Changes to
the surface profile of the skin caused by the forma-
tion of fine lines and wrinkles increase with age
primarily as a result of UV-exposure. However, it
must be noted that wrinkles do not result from
these changes but are superimposed upon them
resulting from structural changes in the epidermis,
dermis and hypodermis. Wrinkles are classified as
atrophic, elastotic, expressional and gravitational
[3], and each type of wrinkle is characterized by
distinct microanatomical changes and each devel-
ops in specific skin regions. Furthermore, different
wrinkles are likely to respond differently to treat-
ment.
Wrinkles are classified to the Fitzpatrick
score [9]:
Fitzpatrick wrinkle score
Class Score Wrinkling Degree of elastosis
I 1–3 Fine wrinkles Mild (fine textural
changes with subtly
accentuated skin lines)
jection method to measure, in 3-D, the depth and
breadth of wrinkles and fine lines (Figs 6 and 7).
Macrophotography: Quality standardized high-
resolution digital photography can visibly demons-
trate facial lines and wrinkles with accuracy. It is
particularly useful for providing accurate before
and after images. The addition of polarization fil-
ters enables a focus on the lines and wrinkles by
removing surface interference such as shine reflec-
tance (Fig. 8a,b).
Invivo confocal microscopy: The primary contribu-
tor to ageing of the skin is photodamage of the
epidermis and dermis. In vivo confocal microscopy
is capable of imaging photodamaged skin and from
those images quantitative data related to short-
and long-term photodamage of the skin are
obtained (Fig. 9). Comparative histological grading
of the structure of the dermis correlates well with
perceived age [10, 11].
Skin pigmentation
Changes to the normal colouration of the skin,
such as age-associated ‘yellowing’ and the appear-
ance of age spots, hormonal changes in females
resulting in melasma, etc. can be measured using
Video microscopy with high resolution digital imag-
ing. Grey scale analysis of the surrounding and
pigmented areas provides an accurate measure-
ment of melanin changes (Fig. 10).
Through Colorimetry, these measurements can
be further supported with the use of a Chromame-
ter, which characterizes skin colour using the
Commission Internationale l’Eclarage (CIE) L*a*b*
colour space, a 3-D representation of human col-
our perception. In this system, a* indicates a point
along the green–red axis, b* the blue–yellow axis
and L* surface brightness (black–white axis).
Practical application of the L*a*b* scale enables
quantification of various colour-based skin charac-

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328 International Journal of Cosmetic Science, 30, 323–332
Clinical perspectives and clinical methods in the evaluation of ageing skin
(a)
Figure 8 High resolution digital
macrophotography of facial wrinkles
in standard (a) and cross-polarized
lighting (b) where removal of
surface shine sharpens wrinkle
imaging.
teristics; hyperpigmentation decreasing the L*
value.
UV-Reflectance photography visualizes and
enhances the results of excess melanin production
caused by UV exposure (Fig. 11). With specific
light filters, UV Reflectance photography enables
observation of areas of pigment density below the
skin’s surface which are difficult to see on the sur-
face of the skin in normal light (approx. 3 mm
below the skin’s surface). Commonly seen parame-
ters with UV photography are: severe freckling
Figure 9 In Vivo confocal microscopy – sparse fine
image of normal collagen fibres in 41-year-old female
skin (with permission, Lucid Inc., Rochester, NY, U.S.A.).
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International Journal of Cosmetic Science, 30, 323–332
T. M. Callaghan and K.-P. Wilhelm
(b)
most commonly seen in very fair skin types; white
spots indicating areas where melanocytes have
been destroyed because of UV exposure; uniform
dark colour commonly seen in darker and Mediter-
ranean skin types.
In vivo confocal microscopy has been employed to
visualize melanocytes within the skin. Pigmented
keratinocytes are seen as polygonal cohesive cells
with variably bright granular cytoplasm. Melano-
cytes appear as bright round, oval, or dendritic
cells (Fig. 12) and are identified by their nested
growth pattern as aggregates of bright round to
oval structures at the dermoepidermal junction or
in the superficial dermis. Melanocytes are also rec-
ognizable as single cells along the dermoepidermal
junction, usually separated from each other by a
variable number of keratinocytes [12, 13].
Skin colour
In addition to skin pigmentation alterations with
age, the underlying skin colour also changes and
these changes in colour tone are perceived by the
consumer as a negative ageing attribute.
Chromophore mapping is a relatively new tech-
nique to measure changes in skin colour tone.
Chromophores, light absorbing molecules below
the skin surface are responsible for colouration
and ‘appearance’ of the skin. The three types
of chromophores – haemoglobin, collagen and
melanin – are crucial in determining perceived
age. Non-contact chromophore mapping using
SIAscopy generates haemoglobin and melanin
329
Clinical perspectives and clinical methods in the evaluation of ageing skin T. M. Callaghan and K.-P. Wilhelm

(a)

(b)

(c) Figure 11 UV-reflectance photography of the skin high-

lighting dense pigmentation as a result of UV exposure,
not seen with the naked eye.

Figure 10 Video microscopy high resolution digital

imaging of age spots (a) normal view and grey scale
imaging of surrounding (b) and pigmented areas (c).

parametric concentration maps enabling investiga-

tion of colour changes with age [14].
RBX is also a similar chromophore mapping
system; the advantage of this technology being
based on a novel colour spaced model capable of
analyzing melanin/haemoglobin deposition across
different skin types [15]. The other advantage is Figure 12 Confocal microscope images of melanocytes
that the tool can be used within existing digital (bright ovoid’s) in the dermis of a benign nevus. Field
imaging systems such as VISIA and OMNIA view 500 · 500 lm (with permission, Lucid Inc.,
(Canfield Imaging Systems, Fairfield, NJ, USA). Rochester, NY, U.S.A.).

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330 International Journal of Cosmetic Science, 30, 323–332
Clinical perspectives and clinical methods in the evaluation of ageing skin
In addition to Chromameter measurements, the
skin’s microcirculation can be further measured
using scanning laser Doppler imaging. By quantifying
skin blood flow, it can provide a relative measure-
ment of clinical and sub-clinical irritation or ery-
thema.
Firmness and elasticity
Of the many undesirable changes in the skin with
age, the loss of skin resilience and skin sagging as
a consequence of both intrinsic and extrinsic age-
ing is very apparent [16]. A number of clinical
methods are available to assess these parameters
based on skin deformation. The Dermal Torque
meter uses angular rotation, whereas the Ballis-
tometer uses an indentation technique. The
Cutometer creates distortion of the skin via
suction. Claims relating to skin firmness and tone
are supported through these methods.
Hair loss
Age-related changes in hair colour, density and
distribution are widely recognized [17]. Greying is
caused by progressive and eventually total loss of
melanocytes from the hair bulb. Scalp hair is
believed to grey more rapidly because its anagen/
telogen ratio is considerably greater than that of
other body hair. With the decrease in the numbers
of hairs with age (Fig. 13), those remaining may
be smaller in diameter and grow more slowly [18].
Hair loss can be evaluated assessing the ratio of
anagen hairs, hair volume, rate of growth and
determination of the number of hairs/cm2. In the
case of female pattern, hair loss scoring is per-
Figure 13 Age-related hair loss in females, scoring
according to a modified SAVIN scale.
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International Journal of Cosmetic Science, 30, 323–332
T. M. Callaghan and K.-P. Wilhelm
formed on a modified SAVIN scale [19] and for
male pattern, on a Norwood-Hamilton scale [20].
Clinical grading
Clinical manifestations of skin ageing are still eval-
uated by trained clinical technicians where
descriptive grading scales (e.g. Fitzpatrick classifi-
cation of wrinkles etc) are used to quantify base-
line and post-treatment parameters. Comparison of
before and after scores enables an evaluation of
the treatment under study.
Combined invasive procedures
Many clinical procedures for the evaluation of the
treatment of ageing skin are often combined with
invasive procedures. Such procedures enable added
value to claim support particularly in those cases,
where perception of product effect needs additional
support. Small skin biopsies can be used to quan-
tify biochemical markers particular to the study in
question, e.g. P53 analysis for photoprotective
effects of a given treatment.
Concluding remarks
Clinical methods used in the assessment of skin
ageing are many and require a disciplined
approach to their use in such investigations.
This work was fully funded by proDERM with
no conflict of interest.
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