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A R T I C L E I N F O
A B S T R A C T
Article history
:
Received: January 31, 2016
Revised: March 25, 2016
Accepted: April 01, 2016
Available online April 03, 2016
Skin is the first business card in human social life. Its structure, texture and color transmit
our status of health and wellness. Unfortunately, wrinkles and sagginess appearing is a
natural phenomenon of life that can affect the human psychological status. Especially
with the increase of the lifetime, and the focus on improving the lifestyle, there is an
increase of patients demanding solutions for the aging signs. Cosmetics act in a scientific
way to find those molecules aiding to maintain the health status of the skin. The purpose
of this review is to consider the wrinkles origin and the treatments that cosmetology and
aesthetic medicine offered so far.
© 2016 Cipriani et al., This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Keywords:
Aging
Skin
Wrinkling
Cosmetics
* Corresponding Author;
E-Mail:sara.bernardi@graduate.univaq.it
Tel: +39 3479801726
Introduction
The skin is well known to be the first element
influencing human socio-cultural relationship. How
we exteriorly look is very important for self-accepting
and for the social life. The skin is where emotions take
place and the expression of health and wellness status.
The color, the opacity and the hydration levels give a
signal of the psychophysical status. The wrinkle is a
furrow on the skin surface. It is due to a progressive
collagen loss, causing a low elasticity of the tissue and
to a lower cellular reproduction (Draelos and Pugliese,
2011). It appears during the natural life course as a
phenomenon known as ageing.
Skin ageing is due to intrinsic and extrinsic processes.
The formers are due to the individual genetic
background, are inevitable and not subject to the
influence of the human behavior. The latters are due
to external factors introduced into the human body,
such as smoking, sun exposure, poor nutrition and
excessive alcohol consumption (Baumann, 2007).
As stated above the skin is the organ that plays a
fundamental role in social life, and a not natural
ageing, the presence of wrinkles, scars and
imperfections lead to the constant research of tools to
slow down the ageing process and to maintain a good
tone of the skin.
Wrinkles classification
The wrinkles are distinguished in (Kligman et al.,
1985):
•Texture
The skin, even the infants’ one, show on its surface a
Advances in Cosmetics and Dermatology
ISSN: Journal homepage: http://www.ajournals.com/journals/acd
Volume 2 (2016) | Issue 1 | Pages 01-07
Open Access
Wrinkles: origins and treatments
Eleonora Cipriani
1
, Sara Bernardi 2*, Maria Adelaide Continenza 3
1 Cosmetologist, Private Practicer, L’Aquila, Italy.
2 DDS, European PhD, Department of Life, Health and Environmental Sciences, University of L’Aquila, Italy.
3 MD, Anatomy Associate Professor, Department of Life, Health and Environmental Sciences, University of L’Aquila, Italy.
Cite this article as: Cipriani, E., Bernardi, S., Continenza, M.A., 2016. Wrinkles: origins and
treatments. Advances in Cosmetics and Dermatology 02, (01): 01-07.
texture composed by depressions or groves, which
intersecting form small rhomboid area.
•Expressional
These are those lines forming on the face where skin
has to adapt to the facial muscles movements.
Indeed, the facial muscles find their insertion beneath
the skin. Consequently, the skin moves together with
them. These cranes are visible at the age of 30, but
they do not increase in number during the years;
instead, they become deeper. Their direction is
perpendicular to the muscular fibers direction.
Due to their dynamism and position, they can be sub
classified in (Figs. 1-2);
-horizontal wrinkle on the forehead, connected to the
activity of frontalis;
-periocular wrinkles, related to the muscle orbicularis
oculi. They result marked in elderly due to the lateral
fall;
-glabellar folds run vertically from the nose root
towards to the forehead. They are due to the
corrugator and procero muscles hyperactivity;
-the naso-labial folds, run laterally from the nose to
the lips angles. The nasolabial fold un-aesthetic when
it is more marked, giving an older aspect to the face.
This accentuation is due to the cutaneous atrophy and
to the ptosis of soft tissues, in particular the malar fat
pad of Owsley. In addition, the mimic activity of
elevator labii gives a great contribution;
-the commissural fold, due to the genien inferior
region ptosis and to the activity of the depressor
anguli oris muscle;
-the peri-labial wrinkles are due to the mimic of
orbicularis oris muscle;
-the geniene wrinkle run vertically from the lateral
cantus of the lips and the mandibular angle. They can
be highlighted by the atrophy of the Bichat corpus.
Figure 1. horizontal wrinkle, periocular wrinkle, glabellar folds
Figure 2. the naso-labial folds, the commissural fold, the
geniene wrinkle and the peri-labial wrinkle
•Joint lines
They are located in the scheletric articulations place
and necessary for the natural movements of the skin.
•Grooves from muscolar skin laxity
They normally appear as part of ageing process, due to
the loss of elasticity of collagen texture. Therefore,
dermis is no more able to contrast the gravity and the
muscle tissue is reduced. This kind of groove appears
normally on the face as the natural fall of the skin. The
treatment in this case is just surgical.
•Lines from sleeping
These folds are created from the lateral position
during the sleep. They appear later on the photo
damaged skin.
Treatments and cosmeceutics molecules in skin
aging
Treatments
The continuous increase of length of life depicts the
necessity to maintain a healthy and young aspect. So
the population look at the aesthetic medicine. When
plastic surgery is not necessary, so-called “non-
invasive” treatments are available (Table 1). These
options are:
•filler;
•peeling;
•botulin toxin;
•lasers;
Table 1. Summary of the methods of treatments in skin aging
(Ganceviciene et al., 2012)
Non invasive
treatments
Filler
Peeling
Botulin Toxin
Lasers
Invasive treatments
Restoration (redistribution)
of fat and volume loss, skin
augmentation and
contouring
Plastic surgery procedures
Cosmetic Care
Daily skin care Correct sun
protection Aesthetic non-
invasive procedures, uses of
antioxidants
Avoiding exogenous
factors
Correct and healthy life-
style
The fillers
The filler is a biological or syntactical mean to inject in
hypoderm or in derma tissue, so to implement or
enhance a limited area of body (usually face) for
aesthetic purpose (Kusin and Lippitz, 2009).
The currently available injectable skin fillers can be
divided into three categories: those that function to
replace tissue lost by the aging process and temporary
duration (collagen, hyaluronic acid, and biologic
fillers); those that stimulate endogenous connective
tissue growth (poly-L lactic acid and
calciumhydroxyapatite); and permanent fillers
(polymethylmethacrylate, silicone, and
hydroxyethylmethacrylate) .
-Temporary filler: they are the most used due to their
temporary effect. The filler is processed and re-
absorbed by the local enzymes. The used substrates
are bovine collagen, autologous collagen, cadaveric
collagen, cell-cultured collagen, hyaluronic acid and
agarose gel (Kusin and Lippitz, 2009).
-Partially absorbable filler: they are constituted by an
absorbable part (usually hyaluronic acid or collagen)
and the other not absorbable (usually composed by
synthetic materials such as dextran beads or poly-
methyl-methacrylate).
-Permanent filler they are synthetic, injectable and
ideally aiming to be permanent without any side. They
are indicated in volumetric correction of deep defects.
They are constituted by acrylics material,
hydroxyapatite and silicones (Buck et al., 2009; Kusin
and Lippitz, 2009).
Peelings
Peeling is a medical treatment consisting in a micro-
abrasion of epidermis or the superficial and medium
derma, by means of chemical or physical agents. This
kind of treatments aim to the revitalizing and
rejuvenating the skin (Fischer et al., 2007; Sánchez-
Carpintero et al., 2010). Both physicians and
nonmedical personnel to improve or correct enlarged
pores, photo-damages, hyperpigmentation, superficial
rhytides, stretch marks, tattoo removal, scar revision,
and acne scarring are using it.
The chemical agents can be distinguished in:
-Superficial peels, affecting the epidermidis and
stimulating the papillary derma. The peels used in
these treatments are pyruvic acid, salicylic acid,
retinoic acid, tricloroacetic acid (T.C.A.) at 10%-20%;
-Intermedium peels, affecting the superficial derma.
They are T.C.A. at 25%, T.C.A. 35%, glycolic acid and
T.C.A. 35%
-Deep peels, affecting the intermedium derma. These
peels are TCA 50% and fenolic based solution.
Botulinum toxin
Botulinum toxin injection for treatment of facial
wrinkles is one of the most common entry procedures
for clinicians seeking to incorporate aesthetic
treatments into their practice. Botulinum toxin is a
potent neurotoxin that inhibits release of
acetylcholine at the neuromuscular junction. Injection
of small quantities of this molecule into overactive
muscles determines a localized relaxation that
smooths the overlying skin and consequently reduces
wrinkles. The effects take two weeks to fully develop
and last three to four months. Treatment of frown
lines and crow’s feet, which are the cosmetic
indications approved by the U.S. Food and Drug
Administration, and horizontal forehead lines, offers
predictable results, has few adverse effects, and is
associated with high patient satisfaction (Bhalla and
Thami, 2006).
Lasers
The cosmetic use of the laser represents a valid non-
invasive intervention for the aged skin. The used
lasers are the CO2 laser and the Er-Yag. They are
indicated for treatments of aesthetic lesions, for
resurfacing, for non-ablative rejuvenating and for hair
removal. These lasers usually are implemented for
face rejuvenating and in acneic patients. The goal is to
vaporize the superficial layers of the skin (epidermidis
and papillary derma) to smooth the external skin. The
side effect of this treatment is the longtime of healing
(Camargo Cristina et al., 2014; Humphreys, 2006;
Sharad, 2013).
Molecules in cosmetology
Vitamin C (I.N.C.I.: Ascorbic Acid-Ascorbil Palmitate)
is well-known and foundamental for its antioxidant
actions as well as being a cofactor in hydroxylation
reactions of collagen production. Vitamin C is also
considered an antiaging ingredient because of its
potential to stimulate collagen production (Hruza et
al., 1993; Teikemeier and Goldberg, 1997). There are
three forms commonly available in cosmetics:
ascorbyl palmitate, magnesium ascorbyl phosphate,
and L-ascorbic acid.
Ascorbyl palmitate, a fat-soluble synthetic ester of
vitamin C, is stable in cosmetic formulas at neutral pH.
Topical ascorbyl palmitate in one study was found to
be thirtyfold more effective than Ascorbyl palmitate,
applied after UV burning, reduced redness 50%
sooner than areas on the same patient that were left
untreated (Manela-Azulay and Bagatin, 2009). The
suspected mechanism is that the ascorbyl palmitate
acted as both an antioxidant and anti-inflammatory
agent.
The Magnesium-L-ascorbyl-2-phosphate, was found
to protect against UVB radiation-induced lipid
peroxidation in hairless mice. The authors found in
vitro evidence that magnesium ascorbyl phosphate
crossed the epidermis and is converted to ascorbic
acid. In an in vivo study of human skin showed 10%
magnesium ascorbyl phosphate cream determined a
clinical improvement of melasma and senile freckles
(Yuan et al., 2005).
L-ascorbic acid is the most bioactive form of vitamin C
and has been found to have numerous benefits for the
skin. This form of vitamin C is water soluble but it
must be formulated at low pH to be stable. In cultured
human skin fibroblast, it increases type I and type III
procollagen mRNA (Kameyama et al., 1996; Lupo,
2011).
Retinol (I.N.C.I.: Retinol-Retinyl Palpitate), or vitamin
A, and its derivates are very popular in cosmetics. It is
particularly indicating for aged skin. The primary
benefit of vitamin A and its derivatives in cosmetic
products consist in the normalizing the keratinization
and in the regulation of epithelial cell growth and
differentiation. This family of compounds showed to
have receptor-specific effects on the skin organ,
resulting in a consequent decreased roughness and
decreased facial wrinkling (Geesin et al., 1988).
Vitamin E (I.N.C.I.: Tocoferol-Tocoferyl Acetate),
potent antioxidant ability. Because of this ability to
quench free radicals, especially lipid peroxyl radicals,
the term “protector” has been used to describe the
actions of vitamin E and its derivatives. Several studies
showed their property to reduce UV-radiation-
induced erythema and edema, sunburn cell formation,
and lipid peroxidation (Pinnel et al., 1987).
Alpha Lipoic Acid (I.N.C.I.: Thioctic Acid) is known to
be one of the most natural powerful antioxidant, the
alpha lipoic acid (LA) is well-defined as a therapy for
preventing diabetic polyneuropathies, and scavenges
free radicals, chelates metals, and restores
intracellular glutathione levels which otherwise
decline with age. Enzymes containing lipoamide are
typically mitochondrial multi-enzyme complexes
catalyzing the oxidative decarboxylation of α-keto
acids (e.g. pyruvate dehydrogenase, 2-oxo-glutarate
dehydrogenase, and transketolase) and glycine
cleavage (Serri and Iorizzo, 2008).
The chemical reactivity of LA is mainly due to its
dithiolane ring. The oxidized (LA) and reduced
(DHLA) forms determine a potent redox couple with a
standard reduction potential of −0.32 V. This
determines DHLA one of the most potent naturally
occurring antioxidants (Trevithick et al., 1992). In fact,
there is evidence that both LA and DHLA are able of
scavenging a variety of reactive oxygen species. Both
LA and DHLA may scavenge hydroxyl radicals and
hypochlorous acid (Devasagayam et al., 1993, 1991;
Scott et al., 1994; SEARLS and SANADI, 1960; Shay et
al., 2009). Neither species is active against hydrogen
peroxide. Furthermore, DHLA appears to regenerate
other endogenous antioxidants (e.g. vitamins C and E)
and has the property of neutralizing free radicals
without itself becoming one in the process.
Hyaluronic acid (I.N.C.I.: Ialuronic Acid-Sodium
Ialuronate) is one of the major elements in the
extracellular matrix (ECM) of vertebrate tissues. It is
available in almost all body fluids and tissues, such as
the synovial fluid, the vitreous humor of the eye, and
hyaline cartilage (Devasagayam et al., 1991; Fakhari
and Berkland, 2013; Suzuki et al., 1991; Vejlens, 1971;
Zheng Shu et al.). This biopolymer functions as a
scaffold, binding other matrix molecules including
aggrecan. It is also involved in several important
biological functions, such as regulation of cell
adhesion and cell motility, manipulation of cell
differentiation and proliferation, and providing
mechanical properties to tissues, skin included. It is
widely used in cosmetic formulations for its
hydratating properties and a filler material
Omega 3 (or PUFA n-3) acids are essential for the
correct body functioning. They are crucial at cellular
levels for maintaining membrane homeostasis, as
ligands for transcription factors thus influencing gene
expression, and for an optimal balance with n-6 fatty
acids to secure a regulated inflammatory response, a
healthy body composition homeostasis and an
equilibrated neurological and psychiatric balance.
Omega 3 have anti-age property: they maintain whole
the cellular membrane avoiding the water loss. In
addition they are used for acne, psoriasis and
dermatitis (Burri et al., 2012).
Natural compounds and herbal products
Phenolic compounds, Flavonoids, and
Proanthocyanidins derived from plants are the main
characters of antioxidative properties of herbal
products. Their chemical structures make them able to
donate free electron and hydrogen (Binic et al., 2013).
The Polypodium leucotomos, extracted from the
tropical Cabbage palm fern and the Camellia sinensis
from the Green Tea act as protection against
photodamages (Binic et al., 2013).
Polyphenolic ellagic acid mostly from berries
prevented proteolytic degradation of existing dermal
elastic fibres and efficiently enhanced elastogenesis in
aged skin. It revelaed to be a promising aid in
curtailing skin wrinkling and cutaneous inflammation
associated with chronic UV exposure leading to
photoageing (Bae et al., 2010) .
Always in the topic of photoageing, Aceriphyllum rossii
extracts have showed to decrease the Matrix
metalloproteinases (MMPs) (Ha et al., 2015) .
A. lappa, A.catechu, D. villosa , C. xanthorrhiza, and S.
japonica decrease the activity of the tissues’
degradation enzymes. In particular, they inhibit
Hyalorunidase, Elastase and Colagenase (Shaheda et
al., 2014) .
Aloe vera (Liliaceae) inhibits the tyrosine hydroxylase
and the 3,4dihydroxyphenylalanine oxidase (Shaheda
et al., 2014).
The combined formulated fruit extract of P. granatum,
G. biloba, F. carica, and M. alba showed a much higher
rate of collagenase inhibition than the efficacy of
individual plant’s fruit extract (Ghimeray et al., 2015).
E. oficinalis, C. asiatica, P.ginseng,and C.zeylanicum act
on the promotion of the synthesis of collagen fibers
(Mukherjee et al., 2011).
For what concern the depigmentation and the skin
enlightment, the Licorice extract, induce skin
lightening by means of melanin dispersion; Raspberry
ketone also inhibits melanogenesis (Binic et al., 2013).
Origanoside from Origanum vulgare has a
depigmentation properties, being an inhibitor of the
melanin synthesis and causing the decline in cellular
Dihydroxyphenyl-alanine oxidase (DOPA oxidase)
activity (Binic et al., 2013).
Topical effect
A good cosmetic product using as ingredient the
molecules listed above, has to satisfy the three gold
standard questions formulated by Dr. Albert Kligman:
1) Can the active ingredient penetrate the stratum
corneum (SC) and be delivered in sufficient
concentrations to its intended target in the skin
over a time course consistent with its mechanism
of action?
2) Does the active ingredient have a known specific
biochemical mechanism of action in the target
cell or tissue in human skin?
3) Are there published, peer-reviewed, double-
blind, placebo-controlled, statistically significant,
clinical trials to substantiate the efficacy claims?
To our knowledge, only the Niacinamide is the
cosmetic ingredient that is closest to the the “Kligman
standards” of cosmeceutical-ingredient analysis
(Levin et al., 2010).
Conclusion
Cosmetology play a fundamental role in aesthetic
medicine, because the modern formulation represents
a valid co-adjuvant to the minor treatments. Modern
cosmetology considers the skin as a proper organ
looking at its anatomy, biochemistry and physiology.
Cosmeceuticals are cosmetic products with
biologically active ingredients with the purpose to
have medical or drug-like benefits. Cosmetics act on a
healthy skin, contributing to its maintaining and as aid
during the ageing process.
Acknowledgments
Authors declare they have no conflict of interest to
disclose
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