cosmetics

Review
Dermatological Management of Aged Skin
Ewelina Rostkowska 1 , Ewa Poleszak 2 , Katarzyna Wojciechowska 2 and Katarzyna Dos Santos Szewczyk 3, *

1 Student Research Group Belonging to Chair and Department of Applied Pharmacy,

Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland
2 Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland
3 Department of Pharmaceutical Botany, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland
* Correspondence: [email protected]

Abstract: The subject of the work concerns the dermatological management of patients mainly with
aged skin. The purpose of the work was to present the basic techniques and preparations which are
performed by dermatologists in the treatment of aged skin. There are dermatological treatments
related to the treatment of skin diseases and cosmetic treatments which are mainly related to skin
care. In this work, the method of literature research was applied. On the basis of books and journal
articles on dermatological and cosmetic procedures for aged skin, an analysis of treatment types
was made. Then, the results of this analysis were presented in the paper under discussion. The
paper presents information on the skin and its properties. The structure and functions of the skin,
aging processes and characteristics of aged skin were discussed. Then, the possibilities of reducing
the visible signs of skin aging through the use of invasive and non-invasive dermatological and
cosmetological treatments were given, and the most important components of preparations used
supportively in combating skin aging processes were discussed.

Keywords: aged skin; skin aging; aging processes factors; skin care methods; cosmetic ingredients;
dermatological treatments

1. The Skin and Its Properties

Citation: Rostkowska, E.; Poleszak, 1.1. Structure and Functions of the Skin
E.; Wojciechowska, K.; Dos Santos The skin, as the body’s coating, performs many functions. It provides protection
Szewczyk, K. Dermatological against external factors such as cold, heat, moisture, bacteria and chemicals. It is flexible
Management of Aged Skin. Cosmetics and stretchy, making it possible for a person to move in complex ways. It transmits
2023, 10, 55. https://doi.org/ nerve impulses about phenomena occurring in the human environment [1]. Therefore,
10.3390/cosmetics10020055
the skin is one of the basic elements of the human body, largely determining its health.
Academic Editor: Francesca Larese Two basic functions of the skin are indicated—passive functions related to the protection
Filon of the body, and active functions, related to regulatory, sensory, defensive and secretory
phenomena. The most important tasks performed by the skin within the framework of
Received: 21 February 2023
passive functions are [2]:
Revised: 16 March 2023
Accepted: 24 March 2023 • protection of the body from the outside temperature,
Published: 27 March 2023 • protection from the harmful range of solar radiation and moisture,
• protection from excessive or dynamic mechanical action—impacts, pressure, friction—as
the skin is flexible and absorbs some of the energy,
• protection from chemicals,
Copyright: © 2023 by the authors. • protection against microorganisms and biological agents.
Licensee MDPI, Basel, Switzerland.
The passive functions of the skin can also include the social function, relating to giving
This article is an open access article
distributed under the terms and
a person’s external appearance and external personal characteristics, which is important in
conditions of the Creative Commons
forming personal social relationships. On the other hand, the tasks included in the active
Attribution (CC BY) license (https://
function of the skin include [2]:
creativecommons.org/licenses/by/ • regulating body temperature through various defense and adaptive mechanisms
4.0/). including the circulatory system,

Cosmetics 2023, 10, 55. https://doi.org/10.3390/cosmetics10020055 https://www.mdpi.com/journal/cosmetics

Cosmetics 2023, 10, 55 2 of 23

• regulating the body’s water and electrolyte metabolism, i.a., through excretory activities,
• participation in the defense mechanism against infections and pathogenic phenomena
• absorption (resorption) activities,
• participation in the metabolism of proteins, lipids, vitamins (synthesis of vitamin D3),
• conduction of sensory information, moisture, temperature, pressure.
Human skin consists of three main layers: epidermis, dermis and subcutaneous
(adipose) tissue, within which are appendages (hair follicles, sebaceous and sweat glands,
nails), as well as blood vessels and nerves. The outer layer—the epidermis—is composed
of cells called keratinocytes, which are arranged in four layers [3,4]:
• stratum corneum—it can be described as the outermost layer of the epidermis. Its cells
undergo continuous exfoliation. It consists of completely flattened, dead, as well as
closely arranged cells without a nucleus (corneocytes). This layer contains compounds
with hygroscopic properties, which are part of the NMF (natural moisturizing factor)
such as amino acids, pyroglutamic acid (PGA) and its sodium salt, urea, uric acid
and glycosamine,
• granular—this is located just below the stratum corneum and consists of several levels
of individual flattened cells; in this part are formed the keratin knots responsible for
the color of the skin,
• squamous—composed of several levels of strongly interconnected cells, this is where
ceramides are produced, which are substances that in the layers of keratinized epider-
mis form the cohesiveness of the skin,
• basal, also called proliferative—this is a row of single cells, i.e., keratinocytes, which
sit directly on the basement membrane. This is a thin zone where the division of
the basal cells of the skin and their growth towards higher layers takes place. In the
newly formed cells there are also specialized cells responsible for the immune system
(Langerhans cells), protecting the skin (melanocytes) and cells working as receptors.
The dermis is about 1–3 mm thick and determines the elasticity and resilience of the
entire skin structure. It consists mainly of protein in the form of collagen (75%) and elastin
(2–4%). This layer of skin also contains hygroscopic substances, for example hyaluronic
acid, that regulate the amount of water in the skin. Proteoglycans provide hydration and
viscosity to the dermis, while elastin is responsible for normal flexibility and elasticity. The
dermis is composed of approximately 60–70% water [5,6]. As we age, human skin contains
less and less water and sags [2].
The dermis also contains sebaceous glands and sweat glands. Sebaceous glands are
distributed throughout the body, and although they perform a similar task, they vary in
size and shape in different zones of the skin. They secrete sebum, which on the surface of
the skin acts as a preservative and lubricant and protects against biological infections [5].
The last layer of skin is subcutaneous tissue. It consists of intertwined, compact fibers
of connective tissue and flakes of fat. Blood vessels that supply the skin also run through
this layer. The subcutaneous layer has thermal insulating properties and protects internal
organs from injury [5].
The general structure of male and female skin is identical. However, there are some
significant differences in terms of its individual components. First of all, men’s skin is
thicker, by about 20–25%, in relation to women’s skin. These differences are mainly due to
the thicker stratum corneum in men, which makes men’s skin rougher and harder to the
touch than women’s skin. Nerve stimuli such as heat and mechanical pressure are less well
conducted by the nerves, but the thicker epidermis and stratum corneum better protect the
skin from mechanical damage and injury [6].
Women’s wrinkles are flatter than men’s, but they appear earlier. Men have deeper
wrinkles, but their formation process is later than in women’s. Male skin has a better blood
supply, and a large number of hairs and adjacent sebaceous glands make the skin oilier,
which can contribute to acne lesions. Some studies [6] indicate higher levels of sebum in
men, which is related to sex hormones. However, there is emerging research indicating that
women’s skin can also show high levels of sebum. Among men, skin pigmentation is much
Cosmetics 2023, 10, 55 3 of 23

higher and there is more noticeable facial sagging in the lower eyelids compared to women.
Skin elasticity among men and women does not differ significantly [6–10]. It is worth
noting that the ways and habits of skin care are influenced by culture. An example is the
Korean culture, in which men show more willingness to take care of their skin compared to
other cultures [10–12].
There are differences between hairy skin and glabrous skin. One of these differences
includes the aspect of touch. Glabrous skin does not have C-tactile (CT) afferents and is
associated more with discriminative touch, whereas hairy skin has C-tactile (CT) afferents
and is associated more with an affective touch [12,13]. The differences between these skin
types are also related to differences in the stratum corneum thickness, the presence or
absence of pilosebaceous units and also the perception [13].

1.2. Human Skin Condition and Aging

The skin is an integral part of the human body and, like the whole body, has a unique,
genetically determined character. Aging processes result from both internal factors, directly
related to a person and his specific organism (endogenous) and external factors (exogenous),
i.e., the environment in which a person lives. The phenomenon of aging involves the
successive weakening of the performance of the body’s cells, which function less well in
terms of metabolic and self-regulation processes and regenerative capacity. Both external
and internal factors have a significant impact on the skin aging phenomenon, and there are
various interactions between them that increase the effect of a particular factor [14].
The endogenous factors that influence the skin aging process are mainly [15,16]:
• natural and genetic predispositions related to aging,
• age—the biggest changes in women occur during menopause,
• general state of health, past skin diseases.
Around the time of menopause, which averages at around 50–52 years of a woman’s life,
the production of estrogen, a sex hormone that is also a regulator of collagen synthesis—the
substance responsible for skin elasticity—decreases [17]. The loss of collagen in the skin is as
high as 30% during the first 5 years after the onset of menopause, and in later years the loss is
about 1–2% per year [18].
In addition, the amount of collagen fibers decreases, they have a different chemical
composition and are corrugated, stiff and irregularly distributed, resulting in a decrease
in skin thickness and loss of elasticity and tension. Due to lower amounts of estrogen, the
ability to create new cells in the basal layer of the epidermis is also reduced. Because of this,
the stratum spinosum and granular layer become thinner. The sebaceous and sweat glands
are also less active during menopause, making the skin dry and rougher to the touch [19].
External factors that affect skin aging include [20,21]:
• improper diet, poor in antioxidants,
• exposure of the skin to ultraviolet (UV) radiation,
• exposure to various chemicals on the skin, associated with being in a contaminated
environment and also passive and active smoking,
• improperly implemented facial care procedures,
• skin diseases—bacterial and viral, the presence of parasites in the skin, etc.

1.2.1. UV Radiation
One of the important external factors that has a major impact on skin aging is UV
radiation, which has the strongest effect on the face and hands. The term “photoaging”
describes the many destructive changes in the appearance, function and structure of the skin
caused by excessive and prolonged exposure to UV radiation and artificial UV radiation,
such as in tanning beds. UVA radiation (wavelength 320–400 nm) and UVB radiation
(wavelength 290–320 nm) are responsible for photoaging. UV radiation penetrates the skin
and leads to harmful effects, which depend on its intensity, wavelength and frequency of
exposure, as well as the occurrence of sunburn. The degree of skin reaction to UV radiation
Cosmetics 2023, 10, 55 4 of 23

depends on the complexion of the skin (skin phototype). Those most prone to skin damage
and subsequent aging are those with class I and II phototypes [22]. However, there is also
evidence that for phototypes III and IV, photoaging may be a cause of skin aging. These
skin types also present a greater predisposition to melanocytic changes, such as melasma
and lentigo [23,24].
It is very important that photoaging of the skin is defined as the aging process that
occurs in this tissue. The process means that any changes may be noticeable and observable
before clinical symptoms appear. This can be used to increase better photoprotection [25].
Sunlight increases photoallergies and contributes to the formation of so-called free
radicals responsible for skin cell aging. Reactions of reactive oxygen species (ROS) with
proteins, lipid-protein membranes and nucleic acids are particularly dangerous. Smoking
also contributes to the generation of free radicals and faster skin aging. The effect of free
radicals is cell damage and destruction of its components. The effects of photoaging include
deep furrows on the skin, nodules and papules. There are also hypertrophic changes,
dryness and roughness of the skin, solar keratosis, deep wrinkles, and telangiectasias.
Harmful effects of UV radiation can manifest themselves at different times in life, even
years later, for example, in the form of cancerous lesions [26].

1.2.2. Blue Light

In addition to UV radiation, a serious threat to the skin is also a part of visible radiation,
so-called blue light (BL), with a range of wavelengths (~400 nm–480 nm). The spectrum of
blue light borders on UVA radiation. It is a heavy energy visible light (HEV) that has an
effect on the skin similar (albeit 4x weaker) to UVA radiation. Shorter wavelength and thus
higher energy light has a more destructive effect on the skin [27,28].
Both UVA and BL radiation cause increased hyperpigmentation of the skin, the for-
mation of spots and hyperpigmentation which results from disrupted melanocytes [27].
In epithelial cells, BL causes the destruction of mitochondrial DNA and increases the pro-
duction of oxygen free radicals and nitrogen free radicals. Increased oxidative stress in
fibroblasts interferes with their division, resulting in reduced collagen and elastin synthesis
and thus premature skin aging [27,29].
HEV rays penetrate deep into the body’s tissues and lead to the activation of free
radicals. This process results in the destruction of collagen and elastin fibers, which are
responsible for skin firmness and elasticity. In addition, free radicals cause the destruction
of skin DNA and lead to the elimination of lipids, or fat cells, which have a very important
role in the issue of skin hydration. In a situation of insufficient lipids, the aging process
becomes faster, and the skin becomes dull, dry and is stripped of its natural color. Facial
hyperpigmentation can also appear, and for this reason people who have a particular
tendency toward pigmentary changes should watch out for HEV radiation. Frequent and
prolonged exposure to HEV radiation can result in an increase in the intensity of irritation
and exacerbation of lesions, so people with sensitive skin should also be careful. In a
situation of regular and frequent use of a phone or computer, care should be taken to
protect the skin accordingly [30].
The skin’s circadian rhythm can be disrupted by excessive BL in the evenings. Skin
cells soothe inflammation and repair damage at night. However, the action of BL can cause
cells to ‘confuse’ themselves and the natural regeneration process can be disrupted [31].
The skin can be protected from the effects of BL in various ways. Some of these may be,
for example, limiting the amount of time that one spends in contact with a laptop or phone;
being able to use such devices that are equipped with a BL filter; using cosmetics that have
a high level of antioxidant potential; and paying attention to ensuring that the diet is rich
in antioxidants, as they are involved in the process of destroying free radicals [31].
Protecting the skin from digital aging primarily involves using cosmetics rich in an-
tioxidants like carotenoids, niacinamide, vitamin E and vitamin C and its derivatives [32].
Vitamin C is a very important antioxidant. This vitamin helps neutralize free radicals,
smoothens the complexion and adds natural vitality. It also participates in the process of
Cosmetics 2023, 10, 55 5 of 23

lightening discolorations on the skin and provides protection against UV radiation. Vitamin
E leads to the process of accelerating the restoration of cells and protects them from the neg-
ative effects of oxidative stress. Niacinamide is a very important ingredient in the process
of skin regeneration, as well as in the process of combating the resulting discoloration [30].

1.2.3. Urbanization Aging

The growth of urbanization as well as the associated increased levels of environmental
pollutants are noticeable in many regions of the world [33]. Air pollutants may include [34–36]:
• gases such as sulfur dioxide, carbon monoxide, nitrogen oxide;
• particulate matter (PM) which is characterized by varying particle sizes, and which
may contain substances such as carcinogenic aromatic hydrocarbons (PAHs) or volatile
organic compounds (VOCs);
• ozone which is formed by the reaction of pollutants with oxygen, with the involvement
of UV action.
Sources of environmental pollution can include coal-fired power plants, car exhaust,
cigarette smoke, and furnaces found in households. There is a growing awareness among
the population of these phenomena and concern about the dangers that may result from
them. Studies indicate that the mentioned factors have negative effects on human health.
In addition, these factors have a high reactivity towards biological structures, including the
condition of the skin. Air pollutants have effects related to a mechanism that is linked to
their activity toward the acryl hydrocarbon receptor (AHR). Several types of skin cells char-
acterize this system, for example, melanocytes, keratinocytes, fibroblasts and Langerhans
cells. External environmental factors lead to its activation, and this leads to the expression
of genes controlling reactions that are related to oxidative stress, immunosuppression,
pigmentation induction, inflammation or premature skin aging [33].
Simple surface interactions of pollutants have the ability to lead to large changes in
the natural composition of the outer structures of the skin layers. There is an increase in the
amount of sebum secreted by the sebaceous glands, as well as a change in its composition
in a negative way. The content of very important components of the lipid layer of the
skin decreases: phospholipids, glucosylceramides, cholesteryl sulfate and sphingomyelins.
There is also an increase in the amount of lactic acid formed and this accounts for the
decrease in the skin’s pH [33].
In addition, environmental pollutants contribute to the reduction of antioxidants, for
example squalene or vitamin E, which are activated to fight oxidative stress, and which
provide protection for the outer layers of the skin [33]. This process leads to the release
of free radicals, which lead to the destruction of hyaluronic acid and the degradation of
structural proteins, namely collagen and keratin, which provide elasticity to the skin and
protect against water loss. Environmental pollutants contribute to damage to the natural
protective barrier, deterioration of the cohesion of the stratum corneum, excessive skin
sensitivity, and increased levels of the erythematous index. Pollutants lead to oxidative
stress, which is a cause of faster aging but can also worsen other existing dermatological
problems, such as psoriasis, acne, atopic inflammation, or even account for the appearance
of skin cancerous lesions [33,35,37].
Cosmetics are increasingly appearing to reduce the negative effects of environmental
pollution. These cosmetics are mainly related to skin care, which helps nullify the negative
effects of pollution. They are, for example [38,39]:
• cleansing cosmetics, whose task is to remove the impurities on the skin;
• antioxidants that replenish those reduced by environmental pollutants and support
the fight against antioxidant stress. This is mainly vitamin C and vitamin E;
• protective cosmetics, which have the effect of protecting against the penetration
of pollutants;
• emollients, whose function is to maintain the integrity of the epidermal barrier
and replenish it, such as ceramides, naturally occurring fatty acids among lipids
and cholesterol.
Cosmetics 2023, 10, 55 6 of 23

1.3. Features of Aged Skin

The first sign of aged skin is wrinkles, which can be deep or superficial (up to 0.05 mm
deep). As we age, wrinkles become more numerous and deeper, which is the result of a
decrease in skin elasticity and loss of fat, water and thus a decrease in the thickness of
the various layers [22]. One of the reasons for less elasticity of the skin after the age of
40 is the body’s cessation of production of ceramides, components of the cellular cement,
which are responsible for proper skin hydration. Atrophy of adipose tissue, most noticeable
in the periorbital, temporal and suborbital regions, is responsible for the skin laxity of
aging skin [40].
Skin aging involves all layers of the skin. The skin’s ability to renew and regenerate
is diminished. Restrictions occur in the metabolic exchange between skin layers, and the
skin’s immune defenses are impaired, making it more susceptible to infection. As the skin
ages, it becomes drier, less smooth and more sensitive to external factors. In aging skin,
elastic fibers become thinner and may even atrophy in the papillary layer so that collagen
is unable to perform its functions. There is also atrophy of vertical vascular loops, resulting
in reduced blood flow, reduced nutrient supply to the skin, impaired thermoregulation,
reduced skin surface temperature and pale skin [41].

2. Opportunities to Reduce Skin Aging Processes in the Beauty Salon

2.1. Invasive Methods
The most commonly used invasive skin care methods include:
• platelet-rich plasma (PRP) treatment,
• needle mesotherapy,
• PDO (polydioxanone) lifting threads,
• botulinum toxin type A injection,
• carboxytherapy.
It must be noted that invasive procedures, such as breaking the continuity of the skin,
must be performed by qualified individuals, such as a doctor. It is important to ensure the
safety and effectiveness of the procedure and to minimize the risk of complications. Only a
qualified doctor has the appropriate knowledge and skills to perform such a procedure.

2.1.1. Platelet-Rich Plasma (PRP) Treatment

Human blood is made up of plasma and the formed elements, or morphotic elements,
which include erythrocytes (red blood cells), leukocytes (white blood cells) and throm-
bocytes. The most important function of platelet cells is to support homeostasis, that is,
to stop bleeding on their own. This function prevents the body from bleeding out and
keeps the blood in the placenta fluid. During treatment with platelet-rich plasma (PRP),
plasma is injected into the human skin, which is enriched with platelets. This results in
tissue reconstruction at the cellular level. The activator for the platelets is the first contact
with collagen, the execution of the injection—that is, the trauma itself—chemicals such as
calcium chloride, the heating of the body’s tissues to an appropriate temperature as well as
UV radiation [42].
PRP is properly prepared for the procedure by a blood centrifugation process. Once
injected under the skin, the process of degranulation of alpha granules in platelets begins
in the tissues. They secrete a growth factor that stimulates skin cells to regenerate. After the
thrombocytes die off, macrophages take over the repair function. Preparing the preparation
begins with the collection of about 10–20 mL of blood from the client into a syringe
containing an anticoagulant in the form of dextrose citrate or sodium citrate. The collected
blood is centrifuged in an angle or horizontal centrifuge. This obtains plasma separated
from morphotic elements. The plasma is separated from the morphotic elements and
placed in a syringe and then the injection is made into selected points of the skin. For full
effect, it is advisable to perform a series of treatments, preferably three with intervals of one
month. Treatment with platelet-rich plasma does not alter facial features and gives natural,
incremental results. Because the client’s blood components are used for the procedure,
 syringe containing an anticoagulant in the form of dextrose citrate or sodium citrate. The
collected blood is centrifuged in an angle or horizontal centrifuge. This obtains plasma
separated from morphotic elements. The plasma is separated from the morphotic
elements and placed in a syringe and then the injection is made into selected points of the
Cosmetics 2023, 10, 55
skin. For full effect, it is advisable to perform a series of treatments, preferably three7with
of 23
intervals of one month. Treatment with platelet‐rich plasma does not alter facial features
and gives natural, incremental results. Because the client’s blood components are used for
the procedure, the risk of allergies and infections is reduced [43]. The platelet‐rich plasma
the risk of allergies and infections is reduced [43]. The platelet-rich plasma treatment has
treatment has rejuvenating and regenerative properties. It restores skin firmness, elasticity
rejuvenating and regenerative properties. It restores skin firmness, elasticity and is used in
and is used in the treatment of acne scars and accelerates hair growth. A double‐blind
the treatment of acne scars and accelerates hair growth. A double-blind placebo-controlled
placebo‐controlled randomized trial showed that PRP was able to significantly improve
randomized trial showed that PRP was able to significantly improve hair regrowth in
hair regrowth in alopecia areata. Results were significantly better after PRP was used than
alopecia areata. Results were significantly better after PRP was used than with placebo and
with placebo and steroid cream [44].
steroid cream [44].
2.1.2. Needle
2.1.2. Needle Mesotherapy
Mesotherapy
An invasive
An invasive procedure
procedure that
that is
is very
very commonly
commonly performed
performed inin beauty
beauty salons
salons is
is needle
needle
mesotherapy. It is performed with a special device or traditionally with a needle
mesotherapy. It is performed with a special device or traditionally with a needle [45]. An[45]. An
example of a needle mesotherapy device is shown in Figure
example of a needle mesotherapy device is shown in Figure 1 [46]. 1 [46].

OP‐N needle
Figure 1. View of the OP-N needle mesotherapy
mesotherapy gun
gun [46].
[46].

This method
methoduses various
uses variouspreparations containing
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hyaluronic or combined
acid alone or
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inorganic or trace
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The product,
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needs, injected intoanesthetized
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anesthetized skin.
tion
The preparation is administered intradermally or subcutaneously. By interrupting the
is administered intradermally or subcutaneously. By interrupting the continuity of the
epidermis,
continuity the healing
of the and reconstruction
epidermis, the healing processes of the skin are
and reconstruction accelerated.
processes of theThe useare
skin of
this method inhibits the loss of collagen, elastin, proteoglycans, as well as Langerhans
accelerated. The use of this method inhibits the loss of collagen, elastin, proteoglycans, as cells.
The
wellmain benefits ofcells.
as Langerhans usingThe
needle
mainmesotherapy are [47]:
benefits of using needle mesotherapy are [47]:
• application of active substances to the
application of active substances to the dermis, dermis,
• nourishing,
nourishing, hydrating
hydrating and and rehydrating
rehydrating thethe skin,
skin,
• improving blood circulation and
improving blood circulation and color, color,
• restructuring of the skin around the eyes,
• thickening and oxygenation of the skin,
• leveling existing wrinkles,
• preventing skin aging and sagging, on the abdomen, thighs and arms,
• contouring of the face.
With needle mesotherapy treatment, the skin is brighter, more hydrated, which al-
lows for a lifting effect. For aged skin, two series consisting of 4–6 treatments per year
are recommended [48].

2.1.3. PDO (Polydioxanone) Lifting Threads

Treatment with lifting threads is often used in aesthetic dermatology. The threads are
made of polydioxanone, which is also used to produce dissolvable sutures in medicine. The
procedure is performed under local anesthesia. Using cannulas or needles, PDO threads are
implanted into the subcutaneous tissue [49]. In the case of tightening threads, a “scaffold”
is created, so to speak, to soften the wrinkles that have formed. Lifting threads pull up the
oval of the face, giving an anti-gravity effect. For a better effect, the thickness and length of
the threads can be selected depending on the size of the face and the thickness of the client’s
skin. Most commonly, 1–3 PDO threads per side are used when using lifting threads. When
using tightening threads, several to dozens of threads per area can be used [50]. The effects
of using lifting threads can be seen as early as three weeks after the procedure. Significant
Cosmetics 2023, 10, 55 8 of 23

improvement is seen after another two to three months. The complete result of thread
absorption occurs one year after the procedure [51].

2.1.4. Botulinum Toxin

The next type of invasive treatment is botulinum toxin type A injection. This is a safe
and effective method of reducing facial wrinkles. Botulinum is one of the most popular
preparations used today in medical and cosmetology offices. Neuromodulators were first
used in medicine in 1950 in neurology and later in ophthalmology. In 2002, botulinum toxin
was approved by the Food and Drug Administration (FDA) for the temporary improvement
of moderate to deep wrinkles. It is used to smooth and shallow wrinkles, as well as to
treat hyperhidrosis or bruxism. Botulism injection causes inhibition of the secretion of
acetylcholine, the neurotransmitter responsible for the conduction of nerve impulses to
muscles. Using a thin 30 G needle, the preparation is injected into the specific muscle
causing the wrinkle, and as a result, relaxing the muscle and reducing the wrinkle. The
effect lasts approximately 4–6 months [52].
Botulinum toxin type A, as well as B, is most commonly used for therapeutic purposes
these days. Examples of preparations that include botulinum toxin type A, which are
registered in Europe, are the following products with their trade names: Botox® , Dysport®
and Xeomin® . In the United States, there is a registered preparation that has botulinum
toxin type B in its composition, and this is a product whose trade name is MYOBLIC® ;
however, the product does not currently have approval for cosmetic use [53]. Nowadays,
interest in the botulinum toxin is growing, and one can also see an increase in the number
of indications for its use. Botulinum toxin has become popular mainly for its anti-wrinkle
effect, which is associated with its wide use in the field of aesthetic medicine. Gradually,
its range of therapeutic recommendations and pharmacological actions is expanding. At
first, botulinum toxin type A received FDA approval for the temporary correction of deep
forehead wrinkles. Allergan’s therapeutic preparation Botox® was used for facial wrinkles
in the upper part of the face. Studies have shown that botulinum toxin treatments are safe,
as well as producing the desired results in terms of correcting facial wrinkles. Usually
within 24–72 h after the procedure, the effect is already visible. Patients who are under
50 years of age achieve the best results with this type of treatment [54]. The development of
research in this field, the expansion of knowledge, as well as the experience gained, has led
to the fact that the use of the toxin has also been extended to the neck, décolleté and lower
face [55]. A preparation containing botulinum toxin is injected into the relevant muscles,
the dose of which is adjusted on an individual basis. Patients are advised to pay attention
to rest after the procedure; it is advisable not to engage in high-exercise activities for a
minimum of two days, and should not undergo facial massages and treatments or laser
treatments for two weeks after the procedure [56]. Neuromuscular disorders, which may
include, for example, pseudomuscular myasthenia gravis, as well as allergy to the toxin,
are primary contraindications to botulinum toxin treatment [57].
The mechanism of action associated with the administration of botulinum toxin is that,
once injected into the appropriate tissue, it binds using a heavy chain to the presynaptic
terminals of cholinergic nerve fibers in the motor plate. The high affinity of receptors
located on the surface of the presynaptic membrane with toxin molecules ensures this
connectivity. Botulinum toxin type A is assigned a receptor, which is a protein fused to the
membrane of the presynaptic vesicle SV2C [58]. When acetylcholine is released from the
vesicle into the synaptic gap, it becomes possible for the SV2C protein to bind to botulinum
toxin type A. The reason for this is that the SV2C receptor is located on the inner part of
the presynaptic vesicle’s membrane surface. The intensity of the toxin coupling process
depends on the number of vesicles that release acetylcholine. The intensity increases if the
number of acetylcholine-releasing vesicles increases. The intensity of the toxin binding
process is greater if the neuromuscular synapse is more active. Botulinum toxin binds to
the SV2C receptor and endocytosis occurs. The light chain characterized by enzymatic
properties penetrates into the cytosol due to the interaction of the endosomal vesicle
Cosmetics 2023, 10, 55 9 of 23

membrane with the hydrophobic domains of the heavy chain of the toxin. The SNAP-25
protein in the cytoplasm is a substrate of the light chain, is part of the SNARE protein
complex and is responsible for the transport and secretion of vesicles with acetylcholine
into the synaptic space. The functions of SNARE proteins are related to the process of
recognition and fusion of the cell membrane with vesicles and the process of vesicular
transport. Among the SNARE proteins is SNAP-25, a synaptosome-associated protein;
there is also synaptobrevin, a synaptic vesicle protein, and the cell membrane-associated
syntaxin. Botulinum toxin type A and its effects are linked to the process of enzymatic
damage in the presynaptic membrane of nerve-end proteins of the SNARE complex. The
toxin’s light chain is responsible for the defragmentation of the SNAP-25 protein [53].
The toxin is the cause of hydrolysis of the SNAP-25 protein, which leads to the process
of cutting off the last nine amino acids; this in turn results in the fact that the release of
acetylcholine from the presynaptic nerve fiber endings of the CNS is inhibited. Muscles
undergo a process of relaxation and the function of the motor neuromuscular plate is
blocked. Changes in the autonomic nervous system can also occur, for example, such as
paralysis of eye accommodation, dryness of the mucous membrane of the throat and mouth
and orthostatic drops in blood pressure [59].

2.1.5. Carboxytherapy
Carboxytherapy is the use of purified carbon dioxide in a controlled manner in various
parts of the body. Such a treatment is used to improve skin elasticity and circulation
in the tissues, as well as to reduce local excess fatty tissue or to improve the cosmetic
effect after liposuction [60]. After application, carbon dioxide is removed from the human
body as a product of gas exchange, that is, naturally. The amount of carbon dioxide
applied in carboxytherapy is comparable to the amount of gas that is produced at the time
of exercise [61].
Subcutaneous injection is related to the injection of CO2 into the subcutaneous tissue
to reduce cellulite, reduce local excesses in adipose tissue and improve blood circulation.
Subcutaneous carbon dioxide injection can be used in the thighs, neck area, abdomen,
supraspinatus, in the ileal area or in the back of the arm. The angle at which the needle
is inserted is 45 degrees. Intradermal injection is associated with the injection of carbon
dioxide to reduce stretch marks, improve the elasticity of the skin of the neck and face, heal
or restore the eye area, improve the skin of the hands, as well as in situations of baldness.
This type of injection can be used around the upper and lower extremities, torso and head.
Injections in the area of the head require special care because there is a disruption of tissues
at the site of the course of many blood vessels and nerves [62]. Carboxytherapy is associated
with the application of gas using a thin needle, so it is a procedure characterized by the
fact that it is minimally invasive. During this treatment, devices that have the function of
regulating the pressure, flow and temperature of the applied gas should be used. Perceived
discomfort during the procedure may be associated with a burning, pressure, spreading
feeling, and the cause of such a condition is the injection and accumulation of gas. After
the procedure, the patient can immediately begin daily activities, though swelling and
mild redness may temporarily persist [63]. Contraindications that are most commonly
mentioned for carboxytherapy procedure are heart disease, pregnancy and severe lung and
kidney failure [64]. Carboxytherapy is a CO2 therapy that is described as an effective and
safe method that results in skin rejuvenation. This treatment is an alternative to methods
characterized by greater invasiveness, such as surgical lifting and laser therapies [65]. Fat
reduction is the main indication for carboxytherapy. This treatment can be the main factor
in the process of reducing local excess fatty tissue, or it can be a complementary factor to the
liposuction procedure, the aim of which would be to increase the intended results and make
the skin smoother. Carboxytherapy is a method that has a mechanical and biochemical
effect. For this reason, it is used for the purposes of correcting the figure, treating skin that
is not very firm on the arms, abdomen and inner thighs, as well as correcting the neck,
décolleté and double chin. Carboxytherapy is very effective in the treatment of scars and
Cosmetics 2023, 10, 55 10 of 23

stretch marks. This treatment stimulates the synthesis of collagen and elastin, leads to
an improvement in blood supply to the tissues and results in the loosening of adhesions
located in the subcutaneous tissue area. CO2 therapy stimulates angiogenesis, and thus
has an effect on fibroblasts, which results in the production of collagen. The new collagen
gives the skin a smoothing effect, improving its appearance [66]. Carboxytherapy is also
one of the most effective methods used in the process of reducing cellulite. This treatment
affects the factors that are the cause of cellulite. Carbon dioxide injection is associated
with an increase in lipolysis and damage to adipocytes, even in cases at an advanced
level. The fibrotic structure is loosened, lymphatic flow is improved, and capillary flows are
increased [67]. Carbon dioxide therapy effectively leads to improved skin tone and elasticity.
Carboxytherapy can be used to reduce wrinkles that appear in the area of the lower and
upper eyelids. There is also a repigmentation process due to an increase in the amount of
oxygen in the tissue and intensification of blood flow, which leads to increased melanin
production. There is a reconstruction of the eye area and a reduction of static wrinkles, dark
circles and fat pads. Carboxytherapy also leads to improved microcirculation, improved
vascular function, reduction and diminution of spider veins, which is beneficial for lower
limb telangiectasias [62]. The effectiveness of carboxytherapy treatment in the area of
cosmetic indications has been proven by numerous studies. The effects of carrying out this
procedure are usually noticeable already at the initial stage of the conducted therapy [68].

2.2. Non-Invasive Methods

Non-invasive or minimally invasive methods are the second group of ways to correct
the skin and its condition in a cosmetics cabinet. These include [69]:
• needle-free mesotherapy,
• application of ultrasound,
• oxygen infusion,
• chemical peels
• micro-needle mesotherapy.

2.2.1. Needle-Free Mesotherapy

Needle-free mesotherapy uses the phenomenon of stimulation of the skin by electrical
impulses. The application of electrical potentials opens channels, allowing active substances
to penetrate into the deeper layers of the skin. This mesotherapy is the least invasive skin
stimulation available on the market. Using the phenomenon of electroporation, it is used
to rejuvenate aged skin [70].
For this treatment, three phenomena occur simultaneously: electroporation, pinocy-
tosis and sonosphere, or micromassage. Electroporation involves the use of a pulsed
electromagnetic wave to destabilize the cell membrane, resulting in the formation of pores
in the membrane [68]. Pinocytosis is the uptake of fluids and nutrients by skin cells through
the convexity of the cell membrane and the tubules formed in it. The molecules of ac-
tive substances contained in cosmetics also work after the treatment, which prolongs its
effectiveness. The most commonly used ingredients for mesotherapy are organic acids,
organic silica, hyaluronic acid, peptides, glutathione and vitamins. The treatment is very
pleasant and painless, dedicated to clients who are afraid of more invasive procedures.
Effects after this treatment include skin rejuvenation, brightening of spots, revitalization,
hydration and skin firming. The treatment takes about 30 min, and is applied once a week
in a series of 5–10 treatments, depending on the client’s skin condition [71]. Needleless
mesotherapy is used to prevent wrinkles, skin aging, to eliminate cellulite, reduce visible
stretch marks, scars, and sagging skin. It is also used for skin firming, body contouring and
to stimulate circulation [70].

2.2.2. Ultrasonic Waves

Ultrasound is sound waves with a frequency of 20,000 Hz. Their high frequency
makes them inaudible to the human ear. It has long been a popular non-invasive method of
Cosmetics 2023, 10, 55 11 of 23

renewal and regeneration of aged skin among clients. Depending on the frequency setting
of the power of such a wave, different depths of the skin can be affected. Ultrasound widens
the intercellular space, which allows for better penetration of active substances contained in
cosmetics used in the treatment. The deep skin massage performed by the device stimulates
cells to regenerate. The treatment has a strong effect on fibroblasts, smoothing wrinkles
and improving skin tone. It is called a ‘lift without a scalpel’ [72].

2.2.3. Oxygen Infusion

A new cosmetic treatment is oxygen infusion. This method involves the injection of
various active substances into the deeper layers of the skin, and the carrier for these sub-
stances is pure oxygen injected into the skin under increased pressure. It is a non-invasive
method by injecting active substances into the layers of the skin, without puncturing. As
a result of such treatment, skin cells are oxygenated and their metabolism is increased,
which increases their energy state and ability to regenerate. More efficient cell division and
expansion of blood vessels (angiogenesis) are achieved, which is important in maintaining
skin tone and firmness. By stimulating fibroblasts to produce collagen and elastin, the skin
gains firmness and elasticity. The effects of oxygen infusion include skin refreshment and
oxygenation, improved skin tone, increased tension and firmness, shallowing of wrinkles
and the acceleration of healing and regeneration processes. It is primarily dedicated to
clients with aged skin that requires immediate regeneration. The effects of the treatment
are already visible after the first treatment, but appropriate home care is recommended
after the treatment in order to consolidate the effect. Oxygen infusion treatment via highly
concentrated oxygen molecules also exhibits strong antibacterial and anti-inflammatory
effects, through which it is recommended for acne-fighting therapies [73].

2.2.4. Chemical Peeling

Chemical peeling is classified as a minimally invasive procedure. It involves the
use of chemicals to remove lesions caused by skin aging or trauma. It is currently the
most popular skin resurfacing treatment. The most common treatments are performed
using combined surface peels. Surface peels separate the corneocytes from the layers of
cells within the stratum corneum, even down to the stratum spinosum. Treatments with
chemical acids achieve improvements in the dermis by stimulating fibroblasts, through
which there is an increase in the production of collagen and glycosaminoglycans. Factors
that affect the depth of penetration of superficial peels depend on the chemical compound
used, the time of application, the client’s skin type and the preparation of the skin before
treatment. Chemical compounds used for this type of treatment include glycolic acid
at a concentration of 20–70%, mandelic acid 50–70%, pyruvic acid 40–60%, salicylic acid
20–30%, trichloroacetic acid (TCA) 10–25%, retinoids and Jassner’s solution. The frequency
of treatments is from 10–30 days in a series of 6–8 treatments [74,75].

2.2.5. Microneedle Mesotherapy

Micro-needle mesotherapy is a treatment that stimulates the epidermis and increases
its permeability, allowing highly concentrated ingredients of the right molecular size to
penetrate deeper and at a higher concentration. Mechanical stimulation stimulates the
skin’s natural regenerative abilities. Micropunctures made with sterile, disposable needles
create several thousand microchannels. Perforation of the epidermis is carried out in
a strictly controlled manner—both its frequency and depth of penetration are adjusted
according to the client’s feelings [76]. During puncturing, blood vessels are damaged, so
that a small amount of blood is released and cytokines are secreted into the extravascular
space, affecting skin regeneration processes. This results in the release of so-called growth
factors, which include [77]:
• transforming growth factor alpha (TGF-α),
• transforming growth factor beta (TGF-β),
Cosmetics 2023, 10, 55 12 of 23

• fibroblast growth factor 2 (FGF-2) and basic fibroblast growth factor (bFGF); these strongly
stimulate fibroblasts to produce proteins that form the extracellular matrix (ECM),
• platelet derived growth factor (PDGF),
• epidermal/epidermal growth factor (EGF),
• connective tissue growth factor (CTGF).
The treatment achieves a lifting effect, improves firmness and elasticity and stimulates
collagen and elastin production. The frequency and number of treatments are adjusted
to the client’s skin needs. The best results are obtained after a series of 3–4 treatments
performed at intervals of 3–4 weeks.

3. Active Compounds of Cosmetics for Aged Skin

The active ingredients present in dermocosmetics for aged skin care are very diverse,
which is related to the numerous theories of skin aging. Their function is to restore a more
youthful appearance and delay and repair skin damage. These substances include cell
stimulators, estrogen-type anti-aging agents, free radical scavengers and sunscreens, as
well as skin exfoliating, strengthening and tightening agents.

3.1. Phytoestrogens
An ingredient of dermocosmetics intended for women of mature age, especially
menopausal women, are phytoestrogens, which are a cosmetic discovery of the 20th cen-
tury. These are plant-derived compounds that show structural similarity to estrogen [78].
The ability to bind to the ER (both ERα and ERβ) is also important in anti-aging cosmetics.
ERβ receptors in the skin are found on keratinocytes, melanocytes, dendritic cells and
vascular endothelial cells. Their role is related to influencing keratinocyte proliferation
and differentiation, facilitating proper keratinocyte adhesion, formation of keratohyalin
deposits, inhibiting IL-12 and TNF-α formation and regulating melanin secretion. ERα
receptors are found on fibroblasts and macrophages. They are involved in the stimulation
of type I and II collagen production by affecting the secretion of transforming growth
factor (TGF-β1) and basic fibroblast growth factor (bFGF) [78]. The potency of these
compounds is weaker than that of 17-β-estradiol. The most important and best known
class of phytoestrogens are isoflavones (genistein, daidzein). Other groups of compounds
belonging to the phytoestrogens include lignans, stilbenes, coumestans, coumarins, as
well as dihydroxychalcones and triterpenoids. Among the isoflavones with the strongest
estrogen-like effects are genistein and daidzein [79], as well as resveratrol [80], a polyphe-
nolic compound belonging to the stilbene group. Phytoestrogens have several biological
mechanisms of action, including antioxidant activity [81,82], reduction of UV radiation-
induced skin damage [83] reduce melanogenesis [84] and improve skin vascularization in
postmenopausal women [85]. These biological properties have found applications in anti-
aging skin care. Studies conducted in vivo have shown the effectiveness of phytoestrogens
against skin aging [86–89].

3.1.1. Isoflavones (Genistein, Daidzein)

The sources of obtaining isoflavones such as genistein, genistin and daidzenin, which
are phytoestrogens, are mainly plants of the Leguminosae family, e.g., Glycine max (L.)
Merr. [90], Pueraria candollei Grah. ex Benth. var. mirifica [91], Styphnolobium japonicum (L.)
Schott (syn. Sophora japonica L.) [92] and Trifolium pretense L. [93]. In 2018, Savoia et al. [94]
demonstrated in their study the protective effect of genistein against peroxidative damage
in fibroblasts and keratinocytes by modulating the release of nitric oxide (NO) and reactive
oxygen species (ROS). Genistein also increased the glutathione (GSH) content and improved
mitochondrial function [94]. Genistein inhibits UVB-induced oncoprotein expression and
reduces the risk of sunburn and tumorigenesis. The efficacy of phytoestrogens is enhanced
by the appropriate chemical form, the use of liposomal carriers and the simultaneous
use of other ingredients with anti-aging effects [95]. From a safety assessment based on
the available aglycone data form of genistein and daidzein, and taking into account the
Cosmetics 2023, 10, 55 13 of 23

potential endocrine effects, the Scientific Committee on Consumer Safety (SCCS) believes
that the use of genistein and daidzein in cosmetics up to a maximum concentration of
0.007% and 0.02%, respectively, is safe [96].

3.1.2. Resveratrol
Resveratrol (3,5,4-trihydroxystilbene) is a polyphenolic phytoelaxin synthesized in
some plants in response to stress factors and fungal infections [97,98]. It occurs naturally in
high concentrations in red grapes, berries (cranberries, black currant, strawberries, raspber-
ries) and peanuts. It is a potent antioxidant, modulator of genetic expression and inhibitor
of inflammatory mediators. It is a potent inhibitor of NADPH, lipid peroxidation and
an effective free radical scavenger, 17 times more potent compared to the Coenzyme Q10
analogue idebonone [97,99]. Resveratrol affects the mechanism of skin aging. It inhibits
damage to the genetic material affecting the proper work of enzymes of the sirtuin class.
Sirtuins (SIRT 1 and SIRT2) are enzyme proteins that normalize a cell’s stress resistance
and repair capacity and prolong cell life. The activity of sirtuins decreases with age [100].
Resveratrol is one of the most effective activators of these enzymes. By increasing their effi-
ciency, resveratrol improves the skin’s natural regenerative processes, as well as enhances
the cells’ resistance to dangerous external factors, including UV radiation. Resveratrol can
also protect the skin from photoaging, reduce lipid peroxidation and reduce leukocyte
infiltration [101]. In human keratinocytes, resveratrol blocked activation of the transcription
factor kappa B (NF-κB) pathway, a protein responsible for intracellular signaling in the
body’s defense pathomechanisms and inflammatory processes induced by TNF-α, IL-1,
IL-6 and IL-8 [102–104]. Sticozzi et al. [105] also showed that resveratrol in vitro protects
human keratinocytes from tobacco smoke. The anti-aging effect of resveratrol was proven
in a study involving 55 women aged 40–60 years. When using a night cream containing
resveratrol (1%), baicalein (0.5%) and vitamin E (1%) for 12 weeks, a marked improvement
in skin firmness and elasticity, smoothing of fine wrinkles and reduction of hyperpigmenta-
tion was observed [106]. Resveratrol, as an anti-aging substance, has an inhibitory effect
on the glycation of supporting proteins in the skin. Glycation involves the destruction
of collagen and elastin by sugars. With age, the level of glycation processes in the body
increases. There is a stiffening of collagen and elastin fibers. Their regenerative capacity
decreases, resulting in increased inflammation and slower healing; at the same time, the
skin takes on a yellowish color. Research on the effectiveness of resveratrol as a comprehen-
sive anti-aging treatment was conducted by Brinke et al. [107]. The purpose of this study
was to evaluate the topical effects of an emulsion containing 2% resveratrol on age-related
skin lesions. The product was applied once a day for 8 weeks, and then selected skin
parameters were evaluated. The results confirmed the anti-aging nature of the resveratrol
emulsion. Indeed, after 8 weeks of regular use, the level of skin elasticity (+5.3%), skin
density (+10.7%) increased, skin roughness (−6.4%) and dispensability (−45.9%) decreased,
and the intensity of skin redness decreased [107]. The indication of the study confirms the
anti-aging nature of emulsions containing resveratrol.

3.1.3. Stem Cell Extracts

With aging, the number of cells in tissues and organs with slowed regenerative pro-
cesses increases. Skin stem cells are responsible for regenerating damaged or worn out basal
layer cells and fibroblasts [108]. High hopes are placed on stem cells in both regenerative
medicine and anti-aging cosmetology [109]. Extracts from plant cell cultures containing a
mixture of active ingredients (primary and secondary metabolites) can be used in minimal
concentrations in the formulation of cosmetics [110]. Clinical studies have proven that
plant stem cell extracts used in cosmetics are readily absorbed by the epidermis, causing an
almost immediate renewal of skin cells. Cosmetic companies are using plant stem cells in
the production of anti-aging cosmetics [110–116]. Plant stem cell extracts are responsible
for many positive cosmetic effects, such as [110,116]: extending the life of fibroblasts and
stimulating their activity (e.g., Oryza sativa L., Gardenia jasminoides J.Ellis); increasing the
Cosmetics 2023, 10, 55 14 of 23

flexibility of the epidermis (e.g., Symphytum officinale L., Capsicum annuum L., Opuntia spp.);
regulating cell division (e.g., Oryza sativa L., Lotus corniculatus L.); rebuilding damaged
epidermis (e.g., Panax ginseng C.A.Mey., Opuntia spp.); activating DNA repair of the cells,
protecting them from oxidative stress (e.g., Rubus ideaus L., Lycopersicon esculentum Mill.,
Citrus limon (L.) Osbeck); and protecting against UV radiation (e.g., Vigna unguiculata (L.)
Walp., Opuntia ficus-indica (L.) Mill.). The first anti-aging plant stem cell extracts from Malus
domestica were introduced in 2008 [117]. Liposomes were used as carriers for the extracts.
An experiment was conducted using human fibroblasts that were exposed to H2 O2 . After
two hours of exposure, the skin fibroblasts had typical signs of aging. Subsequently, one
part of the cells was placed in a 2% apple (Malus domestica stem cell) stem cell extract, while
the other, a control sample, was placed in a neutral environment. The results of the experi-
ment showed that the apple stem cell extract reversed the aging process of the fibroblasts
and led to the stimulation of the expression of the antioxidant enzyme hemeoxygenase-1,
while in the control sample the fibroblasts were irreversibly damaged [117]. When used
as an ingredient in cosmetics, apple stem cell extract shows great potential for reducing
wrinkles in the eye area, the so-called ‘crow’s feet.’ Using an eye cream with the extract
reduced the depth of wrinkles after 2 weeks by 8%, and after 4 weeks by as much as
15% [118]. Polish scientists from Wroclaw have isolated stem cells extracted from red deer
antlers (MIC-1). They are pluripotent cells and can differentiate into all cells that make up
the antler: osteocytes, chondrocytes, neurons, fibroblasts and keratinocytes. Using stem
cell culture from deer antlers, a new complex for cosmetic use was developed. In addition
to MIC-1 cells, the complex contains unsaturated fatty acids, phospholipids and collagen
peptide active factors, mineral salts and sugars in its composition. The complex contains
growth factors that stimulate fibroblasts and specific epidermal stem cells. This leads to
natural skin renewal [119]. After the application of cosmetics containing active substances
from deer antlers, the density, firmness and elasticity of the skin increase and wrinkles
become shallower. The process of bio-renewal of the dermis and basal layer that occurs
after using the products contributes to skin rejuvenation [120]. Stem cell extracts are very
good ingredients to cosmetics designed for aged skin care.

3.1.4. Vitamins
Vitamins play a very important role in slowing down the aging process, especially
those with strong antioxidant potential such as vitamin A and its derivatives—retinoids, vi-
tamin C, vitamin E and coenzyme Q10. Cosmetics containing vitamins in their composition
have a multidirectional effect. They not only inhibit the formation of oxidative stress in the
skin, but also protect against the adverse effects of external factors, the so-called extrinsic
aging. Cosmetics rich in antioxidant vitamins prevent inflammatory processes underlying
the aging process [121].

3.1.5. Vitamin A and Its Derivatives—Retinoids

Retinoids are among one of the most effective and widely used ingredients in anti-
aging cosmetics. They exhibit a lipophilic nature, so they penetrate the epidermal barrier
very easily, passing into the deeper layers of the skin. Vitamin A derivatives have a smooth-
ing effect on the skin, as well as making it more elastic. It eliminates fine wrinkles, reduces
hyperpigmentation and increases the production of collagen fibers; the number and activity
of fibroblasts reduces the activity of metalloproteinases and also improves skin angiogen-
esis [122]. Retinoids stimulate the synthesis of collagen I, III, VII, as well as procollagen
I and fibrillin. They promote collagen remodeling, and stimulate the proliferation and
differentiation of epidermal cells, resulting in an increase in the cohesiveness of the stra-
tum corneum and thickening of the granular layer. They inhibit tyrosinase and limit the
transfer of melanosomes, increasing the exfoliation of melanocytes so that hyperpigmen-
tation becomes less visible. The complex mechanism of action of retinoids makes deep
wrinkles shallower, skin radiant, well-hydrated, smoother, more elastic and smoother to
the touch [123]. The most common forms of vitamin A in cosmetics include retinol and its
Cosmetics 2023, 10, 55 15 of 23

esters, palmitate and retinyl acetate, and β-carotene [124]. Due to safety reasons (risk of
teratogenicity), the Scientific Committee on Consumer Safety, Secretariat at the European
Commission, Directorate General for Health and Food Safety recommends a maximum
retinoid concentration of 0.05% retinol equivalents (RE) in body lotions and 0.3% RE in
hand and face creams, as well as other leave-on or rinse-off products for cosmetics in the
EU [124]. Rakuša and Roškar [121] studied 35 cosmetic creams containing various retinol
derivatives. The content of the active ingredient per retinol ranged from 160 ng/g–19 mg/g.
The application of cosmetic formulations containing retinol or its derivatives is one of the
most effective methods of preventing skin aging [123].

3.1.6. Vitamin C
Vitamin C and its modified molecules protect the skin from oxidative damage, rejuve-
nate photoaging skin, brighten skin, have anti-inflammatory effects and reduce erythema
after sun exposure or laser treatments. The anti-aging effect of vitamin C is due to the fact
that it is essential as a cofactor for the enzymes lysyl hydroxylase and prolyl hydroxylase,
which are essential in the biosynthesis of collagen (types I and III). Thus, by stimulating
these stages of biosynthesis, ascorbic acid will increase collagen production, leading to
wrinkle reduction [125]. Topical application of vitamin C increases levels of tissue inhibitors
of collagen-degrading matrix metalloproteinase 1 (MMP-1) [126]. Garre et al. [127] reported
that the application of a cosmetic formulation containing ascorbic acid to skin sections
in vitro protected against oxidative damage and photoaging-induced protein loss. In tests
on study participants, it provided very good skin hydration, and brightened and smoothed
the skin [128]. The beneficial properties of vitamin C make it a popular choice for use
in anti-aging and regenerative cosmetics [111]. Topical application of vitamin C is the
cornerstone of anti-aging management [88]. There are several forms of vitamin C used in
cosmetology. The first, non-permanent form is the active form of vitamin C, L-ascorbic acid.
To increase the durability of cosmetics containing ascorbic acid, its esterified derivatives
are used: ascorbyl tetraisopalmitate, ascorbyl palmitate-6-ascorbyl palmitate, ascorbyl
phosphate magnesium and sodium salt [128–130]. Exposure to UV rays reduces vitamin
C content in the skin by about 70%. External application of this vitamin protects the skin
from the dangerous effects of UV radiation, especially when using vitamin C, vitamin
E and ferulic acid simultaneously [129]. Vitamin C stimulates ceramide synthesis and
increases the amount of TIMPs-tissue inhibitors that inhibit MMP1 metalloproteinase [129].
A study of 19 people aged 36–72 with moderately UV-damaged facial skin showed that
regular use, over a 3-month period, of a preparation containing 10% ascorbic acid improves
the overall appearance of the skin, reduces roughness and minor skin defects, shallows
wrinkles, increases flexibility of the skin and unifies skin tone by reducing significant skin
yellowing, compared to a control group that used the base alone for the same period of
time [129]. In the care of aged skin, L-ascorbic acid derivatives perform better, among which
lipophilic ascorbyl tetraisopalmitate is the most durable. It can be used in formulations
in combination with retinol and ferulic acid, thus significantly increasing the anti-aging
and brightening properties of the compound. Unlike ascorbic acid, it can be used for
sensitive skin [128].

3.1.7. Vitamin E
Vitamin E is considered the most important lipophilic exogenous antioxidant. Vitamin
E is used in cosmetics as an active ingredient, with occlusive and emollient action [131]. It
is also stabilizer of other, non-permanent components of a cosmetic product [106,132]. It
builds into cell membranes, prevents oxidative stress-induced peroxidation of cell mem-
brane lipids and reduces UV-induced erythema and swelling [106]. It also exhibits strong
anti-aging properties [133,134]. According to studies, α-tocopherol has better antioxidant
properties compared to tocopherol esters, which require prior hydrolysis in the skin [121].
In their research, Rakuša and Roškar [121] determined the concentration of tocopherol in
49 cosmetic formulations. Tocopherol was present in them at a concentration of 8.5 µg/g to
Cosmetics 2023, 10, 55 16 of 23

16 mg/g. It has also been shown that when using a formulation with tocopheryl acetate
every day for five consecutive days, it is possible to fully inhibit erythematous lesions
resulting from the influence of UV radiation [128]. In addition, vitamin E, present in cos-
metics, supports the reconstruction of damaged tissue, increases blood supply to the skin,
improves the elasticity of the connective tissue and accelerates the processes of collagen
and elastin biosynthesis occurring in the dermis [128].

3.1.8. Coenzyme Q10, Alpha-Lipoic Acid and Idebenone

A natural antioxidant that is a quasi-vitamin is ubiquinone, otherwise known as coen-
zyme Q10 [135]. The content of coenzyme Q10 in the skin is relatively low. There is 10 times
less ubiquinone in the dermis than in the epidermis, so the epidermis can benefit from
topically applied ubiquinone [136]. Coenzyme Q10 also acts as an antioxidant in the skin.
It protects glutathione from its breakdown, slows DNA damage in keratinocytes, increases
glycosaminoglycans and protects collagen from breakdown. Ubiquinone minimizes the
symptoms of extrinsic and intrinsic aging [128]. Coenzyme Q10 in the form of ubiquinone
is a popular ingredient in anti-aging cosmetics, among others, in which it is usually found
in concentrations of ≤0.05% [137]. An analog of coenzyme Q10, idebenone, is also used
in cosmetics. It exhibits antioxidant activity comparable to lipoic acid and stronger than
ubiquinone [128]. Creams with alpha-lipoic acid smooth fine wrinkles, reduce photoaging
lesions, reduce the intensity of hyperpigmentation and reduce inflammatory reactions [128].

3.1.9. Plant Extracts

Plant extracts are very good for daily skin care, and because of their wide range of
applications, plant extracts are called one of the multifunctional cosmetic ingredients [138–140].

3.1.10. Extract of Scutellaria baicalensis Georgi (Lamiaceae)

Scutellaria baicalensis extract is widely used in cosmetics dedicated to aged skin. It can
also be used as a cosmetic ingredient for whitening, sun protection and anti-aging [141,142].
Following the discovery of Hayflick’s theory, scientists sought to find a way to activate
telomerase in somatic cells. They isolated a natural substance found in the roots of S.
baicalensis, baicalin, which increases telomerase expression [143]. The activation of telom-
erase by baicalin has only been discovered in recent years. In vitro studies proved that
aging fibroblasts housed for 2 months in a baicalin environment restarted their divisions.
This was due to the elongation of the DNA strand that forms the telomere [143]. Using
baicalin extracted from S. baicalensis, the anti-aging raw material was developed to prevent
cellular aging by stimulating telomerase expression in fibroblasts. The effect of baicalin on a
50-year-old person would be to rejuvenate her skin fibroblast population by 10 years [142].
Baicalin has been shown to delay fibroblast aging by increasing the number of cell divisions
by 10%, assuming that the total number of fibroblast divisions is 50. According to the
above experiments, it was noted that the test substance restores fibroblast activity to a
state comparable to skin ten years younger [141]. In in vivo tests, the positive effect of
baicalein on the skin was confirmed. The study was conducted in a group of 20 women
aged 35–45 years. After two months of using a cream with baicalin-containing raw material,
an increase in skin elasticity and firmness of about 12.5% was noted. An improvement
in the skin microsculpture and 13% reduction in wrinkles was observed [142]. The raw
material has become a very promising product in anti-aging medicine. This modern and
advanced extract can be successfully used in anti-aging and rejuvenating formulas. It has
a beneficial effect on the skin, improving its appearance, as well as its condition, while
delaying the aging process [142].

3.1.11. Centella asiatica Extract

Centella asiatica L. Urb. (Apiaceae) extract is used in cosmetics for aged skin due to its
valuable anti-aging, anti-inflammatory, anti-bacterial and collagen synthesis stimulating
properties [139,140]. Active substances belonging to the group of bioflavonoids (quercetin
Cosmetics 2023, 10, 55 17 of 23

and kaempferol), phytosterols, triterpene saponins (madecasoside and asiaticoside), among

others, have been isolated from the plant [139]. Madecasoside soothes and reduces the
allergic reaction in the skin caused by external factors. In addition, it stabilizes collagen
fibers and increases cell proliferation. Asiaticoside stimulates cell granulation, accelerates
regeneration and scarring processes, inhibits hyaluronidase and stimulates the synthesis of
glycosaminoglycans in the skin [139]. C. asiatica extract activates fibroblasts to biosynthesize
collagen (mainly type I collagen) and elastin. Due to its effects, it is widely used in anti-aging
cosmetics. When applied to the skin, C. asiatica extract reduces wrinkles. It also exhibits
antioxidant and antioxidant activity and accelerates angiogenesis. Asiatic acid present in
the plant extract increases the synthesis of collagen and proteoglycans increases wound
healing. The valuable moisturizing properties of C. asiatica are confirmed by numerous
scientific studies [139,140].

3.1.12. Bakuchiol
Bakuchiol is a plant-derived substance that is used by cosmetics manufacturers as
an ingredient of anti-aging preparations. It is a meroterpene phenol found mainly in
the seeds of the Indian plant Psoralea corylifolia [144,145]. Research results published by
Chaudhuri and Bojanowski [146] showed that retinol and bakuchiol have a similar gene
expression profile, especially in key genes and proteins which act as countermeasure for
aging. Bakuchiol, unlike retinol, has an excellent photochemical and hydrolytic stability,
and a good safety profile. It can be used during the day due to its photostability [146].
Studies conducted by Chaudhuri and Bojanowski [146] have shown that the regular use
of a cream containing 0.5% bakuchiol for 12 weeks significantly improves the smoothness
of the skin and reduces the appearance of fine wrinkles. In addition, preparations with
bakuchiol brighten the skin and reduce sun discoloration [147]. It can be used even in
people with very sensitive skin [148].

3.1.13. Peptides
Peptides are very popular cosmetic ingredients. Glutathione (γ-glutamyl-cysteyl-
glycine) is a GSH tripeptide which is one of the first peptides used in cosmetology. It
contains the amino acid cysteine -SH, which gives this molecule its antioxidant activ-
ity. Glutathione levels in the body decline markedly with age, which contributes to
skin aging [149]. Glutathione is also helpful in eliminating skin discoloration of various
etiologies [149]. Carnosine (β-alanyl-l-histidine) scavenges reactive oxygen species (ROS)
formed by the peroxidation of cell membrane fatty acids during oxidative stress. Carnosine
has also been shown to prevent the effects of protein glycation, which leads to damage
and fragility of collagen fibers [150]. Another popular stimulating peptide belonging to the
matrikines family that is often used in cosmetics is (a fragment of the type I procollagen
sequence of) the Pal-KTTKS pentapeptide. It is found in combination with palmitic acid,
to which it owes its good penetration through the skin; the main function of this peptide
is to increase the production of type I and II collagen and fibronectin [151]. Tetrapeptide
Arg-Gly-Asp-Ser (RGDS) is the structure of fibronectin responsible for the ability of this
protein to bind to collagen and cell membranes, thus accelerating wound healing. The cyclic
peptide RGD, on the other hand, binds to integrin receptors, thus showing anti-wound
healing properties [151]. The Pal-Gly-Gln-Pro-Arg peptide (Pal-GQPR) is a fragment of
a natural circulating IgG protein which contributes to the reduction of UV-induced IL-6
release in keratinocytes and fibroblasts, leading to improved skin firmness [152]. Peptides
in cosmetology represent a novelty in the prevention of skin aging. They are distinguished
by their ability to penetrate the epidermis and reach the deep layers of the dermis. Peptides
are involved in many skin processes: stimulation of protein synthesis, melanin production,
migration of pro-inflammatory cells, modulation of fibroblast proliferation, as well as
formation of capillaries. The effects of the peptides are visible only after 8–12 weeks of
regular use [152]. It manifests itself by increasing the firmness and elasticity of the skin,
strengthening the blood vessels present in the skin, reducing irritation and reducing the
Cosmetics 2023, 10, 55 18 of 23

appearance of facial wrinkles. In addition, the peptides stimulate mechanisms that protect
the skin from harmful UV radiation and also prevent the formation of facial wrinkles at an
early age [152].

4. Summary
The skin is the largest human organ, and the signs of aging, a natural biological process,
are clearly visible on it and become more pronounced with age. The result of these processes
are wrinkles, and the main causes of wrinkles are the loss of collagen, loss of hyaluronic
acid and weakening of the hydrolipid barrier of the epidermis. The dermis, thanks to its
high content of collagen and hyaluronic acid, maintains its cohesion, density, elasticity,
flexibility and firmness, which is what determines its youthful appearance. Additionally,
skin is exposed to external factors such as UV radiation, smog (fine suspended particulate
matter, PM 2.5), and free radicals on a daily basis, which can accelerate the aging process.
The main problem with aged skin is the progressive atrophy of the skin, associated with
degenerative processes in all its layers. The loss of body fat on the face makes it look tired
and sunken. Its susceptibility to mechanical deformation increases, and hyperpigmentation
intensifies. To solve these problems, both invasive and non-invasive methods of skin
treatments are available. Invasive methods performed by a dermatologist, such as PRP
treatment, needle mesotherapy or botulinum toxin injection, may provide faster results,
but are associated with a greater risk of complications and allergic reactions. On the
other hand, non-invasive methods, such as needle-free mesotherapy, ultrasound, oxygen
infusion, chemical peels and micro-needle mesotherapy are less risky, but may take longer
to see results. Ultimately, the best approach for the patient will depend on their individual
problems and skin preferences. In addition to salon-based care for aged skin, it is also
important to have a properly selected cosmetic daily routine. Cosmetics used on a daily
basis should provide appropriate moisture, UV protection, combat free radicals and act
regeneratively. Ingredients that prevent the negative effects of oxidative stress on skin
are vitamin C, vitamin E and coenzyme Q10. Baicalin, obtained from the Baikal skullcap
(Scutellaria baicalensis), and retinol or its plant-based counterpart bakuchiol have very
good anti-aging properties. Regular and long-term use of these ingredients allows the
improvement of the appearance of the skin, reducing the visibility of fine wrinkles and the
negative effects of free radicals on the skin.

Author Contributions: Conceptualization, E.R. and K.W.; writing—original draft preparation, E.R.
and K.W.; writing—review and editing, E.R., K.W., E.P. and K.D.S.S.; supervision, K.D.S.S. and E.P.
All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data available on request.
Conflicts of Interest: The authors declare no conflict of interest.

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