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Prepared
by: Dr. Charlene DeHaven, Clinical Director
HOW DAMAGED SKIN DIFFERS FROM NORMAL SKIN
The changes of aging on skin appearance are obvious.
Wrinkling, as it develops in an individual over time, is visually
obvious. There are also biochemical and functional differ-
ences that develop in skin as time advances. These visual,
biochemical and functional changes of aging do occur in all
of us, given enough time. They are related to sun exposure,
toxin exposure (such as smoking), other diseases (such as
diabetes, heart disease, cancer) and oxidative stress
(excess free radical damage). Each individual may delay or
hasten the development of these changes according to
various “life style” factors. These include taking antioxi-
dants, limiting sun exposure, modifying diet, etc. For all
intents and purposes, aged skin is the same as damaged
skin. However, within the category of “aged skin” are two
groups that do differ somewhat from each other; these are
aging without sun exposure and aging in sun-exposed
areas. We usually think of “damaged skin” as occurring,
perhaps, at a younger age and “aged skin” as exhibiting
visual changes about where we would expect in accordance
with the individual’s age. However, the skin of a thirty-year-
old individual may have an “aged” appearance equivalent to
most fifty-year-olds because “damage” was accelerated and
no steps were taken to protect against it. Young individuals
with older-looking skin may have damaged their skin by
intense or repetitive sun exposure or toxin exposure, such
as cigarette smoking.
Let’s do briefly clarify the changes of aging seen in sun-
exposed areas and non-sun-exposed areas. You can
visually conceptualize the differences here by thinking of the
appearance of aged skin on the abdomen (an area usually
protected from sun exposure) and on the back of the neck or
the forearms (sun-exposed). Thinking biochemically, in
general terms, the areas protected from the sun have
sustained damage related to “pure aging”. Biochemically,
“pure aging” would be associated with the free radical
damage of ongoing cellular metabolism and its conse-
quences, including defective protein synthesis. The aging
changes of sun-exposed skin would include “pure aging”
plus the additional radical damage from solar radiation. Skin
protected from the sun is thin and smooth, evenly pale, with
fine wrinkling, few malignant lesions, inelastic and saggy,
and exhibits increased fragility. Aged skin in sun-exposed
areas is more thickened and nodular, exhibits coarse
wrinkling and rough texture, has mottled pigmentation, is lax
and inelastic as well as dry and scaly, has pronounced fragil-
ity and bruises easily, and has a marked tendency to
develop malignant growths. Interestingly, keratinization is
not altered with age alone. This is particularly interesting
considering that keratin is a protein and synthesis of most
proteins becomes defective with aging.
Wrinkling is the most visually obvious
of the changes of aging in solar-exposed areas. There
are various types of wrinkles, ranging from very fine
to deep. The deep wrinkles are the most problematic because
their treatment requires the most invasive methods, i.e.
surgical correction. If aged skin is viewed under the
electron microscope (a micro- scope with extremely large
magnification), the elastin fibers are seen to be altered.
This occurs because of oxidative stress and glycation,
which damage them. The damage may be due to “normal” aging
or may be accelerated by excessive sun exposure, other
diseases, toxins, etc. Elas- tin is a protein that is
“elastic”, as its name implies. When the skin is stretched,
as in smiling or with other facial motion, the elastin
fibers cause the skin to recoil back to its original shape.
If the elastin is damaged, it functions poorly in this
regard and the skin looses its youthful elasticity. Consequently,
wrinkles begin to develop due to the inability of the
skin to resist the effects of gravity and its inability
to return to normal shape after facial muscle motion.
Colla- gen, a protein within the dermis that imparts strength
to the tissue, also becomes defective with aging. Collagen
content decreases by about 1% per year through adult life.
Proteoglycans, the substances holding the collagen bundles
together, also decrease with age. In addition to supporting
collagen, proteoglycans, such as hyaluronic acid, bind
large amounts of water. Fewer proteoglycans mean less
ability to hold hydration, leading to a dry leathery appearance.
The development of wrinkling follows the “skin lines”
which correcpond to the direction of the under- lying
muscle fibers. In addition, the downward force of gravity
also exerts its pull on the skin. As damage occurs, the
skin is increasingly less able to oppose the force of
gravity. This downward sagging of the face results in
the typical tired or angry appearance of the aged countenance.
The cellular components of the skin also tend to decrease
in number with aging. Fibroblasts are the cells which
synthesize collagen. Fibroblasts also decrease with aging
and express decreased amounts of procollagen (collagen
precursor) and increased amounts of collagenase (an
enzyme which degrades collagen). Less procollagen and
more collagenase results in a decrease in the overall
amount of collagen found in the dermis of the aging person.
There are fewer melanocytes (pigment-producing cells) in
aged skin. However, in solar-damaged skin, the melano-
cytes that are present are over-stimulated. This combina-
tion of over-stimulation and fewer overall melanocyte
number leads to the mottling pigmentation of aged solar-
damaged skin. Within the rete pegs at the dermal-
epidermal junction are found the stem cells responsible for
regeneration of epidermal cells. The rete pegs are
flattened and there are fewer stem cells, which leads to the
decreased regeneration of the epidermal cells.
As we age, our ability to repair damaged tissues deterio-
rates. All tissues become damaged as a consequence of
living in our environment. For example, a muscle may
become bruised. A bone may be broken. This damage may
be very minor (as a slight bruise) or major (as a surgical
procedure). All living organisms have repair mechanisms to
correct damage and return to optimum functioning. With
oxidative stress (aging), these repair mechanisms are less
able to function in the exact way they were intended. In
order to repair and rebuild damaged tissue, protein synthe-
sis is required. DNA within each cell directs the synthesis of
the type of protein that cell is supposed to produce. For
example, DNA within cells in the dermis of the skin directs
the formation of new elastin to replace or repair the elastin
that has been damaged. If the DNA itself has been
damaged by oxidative stress, it is unable to clearly direct
proper protein synthesis. The formation of defective elastin
leads to its ineffective functioning. In other words, the new
elastin made is not “elastic”. This defective elastin cannot
prevent architectural changes in the face from gravity and
wrinkles develop. It is estimated that by the time a person
reaches 60, and with an average rate of aging, that
individual is able to synthesize about one-half of the protein
they could at the age of 20. No wonder we all begin to look
old and our tissue functioning begins to fail as aging
progresses. We are not able to manufacture the correct
proteins to facilitate repair of damaged tissues to the same
degree as when we were younger. A microscopic slide of
aged sun-exposed skin shows the characteristic findings of
“solar elastosis”. This solar elastosis is the result of free
radical damage from solar radiation on the elastin bundles
combined with the increasingly ineffective protein synthesis
of the aging organism. Under the microscope, we see
defective bundles of elastin that are characteristic of aging
solar-damaged skin.
Wrinkling may be the most obvious change associated with
aging in sun-exposed areas but others also occur. The
layers of skin become thinner, particularly the dermis. The
dermal-epidermal junction flattens and the rete pegs that
interdigitate the dermis and epidermis become blunted. This
blunting results in a decrease in surface area of the dermal-
epidermal junction. This lessens the force holding the two
layers together, making it easier for the dermis and epider-
mis to separate with trauma. Thus, blistering occurs more
readily, superficial skin tears occur more frequently and with
less force.
These microscopic changes are also visible and make the
skin look older. As we might expect, these visible structural
changes are associated with alterations in skin function
which are described below.
Alterations in Barrier Function—Right
now, there is no clear consensus as to how structural
differences in the epidermal barrier translate into functional
differences seen with age. We do know quite a bit about
the structural differ- ences of older compared to younger
epidermis. With aging, the thickness of the epidermis
decreases slightly, although the most pronounced decrease
in thickness occurs in the dermis. Since the number of
total cells appar- ently does not change, this means that
the epidermis becomes more compact. Also, the surface
area of the junction between the epidermis and dermis
decreases because this epidermal-dermal junction flattens.
Water content of the stratum corneum decreases with aging.
Visually, older skin appears drier than youthful skin
and is also more subject to the effects of dehydration
since it contains less water to begin with. In aging skin,
the proteo- glycans (such as hyaluronic acid) which hold
water decrease and moisture content also goes down. The
amount of lipids (fats) in the epidermis of older persons
is less than in younger. When these various changes of
aging skin are considered, it might seem that some would
increase the absorption of substances through aging skin
and some might cause a decrease. Evidence indicates that
the overall effect depends on whether the substance to
be absorbed (carried) through the skin is hydrophilic
(meaning water-loving or itself containing water) or lipophilic
(meaning lipid-loving or fat-loving or itself contain-
ing lipid). All types of substances make their way through
the epidermis by a lipid-rich pathway. In these types
of passive transport, like attracts like; for example,
oily substances merge with other oily substances but not
with watery substances. Lipids (oils or fats) attract
lipids and merge with them. The lipid rich transport system
therefore is ready to merge with and transport other lipids
(fats) and less ready to merge with and transport watery
substances. For the substances rich in water, the decreases
in lipid content of older epidermis mean an increase in
transport through the epidermis for these substances.
Substances of this nature include caffeine and salicylic
acid. For the oilier substances we might expect an increase
in transport through the older epidermis. Surprisingly,
however, the transport rates of oily substances, like
the hormones estro- gen and testosterone, is about the
same in older and younger epidermis. The discussion above
illustrates the many variables that relate to skin absorption
and water content. Some of these are clearly conflicting.
Right now, researchers are not in agreement as to the
overall differ- ences in absorption through the epidermis
of older versus younger persons. We can say that more
watery substances are transported more rapidly, however,
and more oily substances move at about the same rate in
younger and older epidermis.
For skincare products, we try to achieve absorption through
the epidermis into the dermis only. It might surprise you that
most skincare products are surface agents only. Their
technology is not sufficiently sophisticated to penetrate the
epidermal barrier. Because of this, they actually do very
little. Unfortunately, they merely sit on the surface. Skincare
products of more sophistication and with a scientific basis,
however, are designed to penetrate the epidermal barrier
and act upon the layers of skin below this barrier.
The skin may also be used to absorb medicines. This is
especially common today with hormones, such as estrogen,
or cardiac medicines, such as nitroglycerin. These medi-
cines can be placed in a cream, gel or serum or can be
placed on a patch which adheres to the skin. Medicines
must travel into the general circulation in order to have an
effect upon the heart or other organs. There are other struc-
tural changes in older skin that affect the absorption of these
medicines into the general circulation. The number of small
blood vessel loops (capillary loops) in the dermis are
decreased in older persons, making the transport of medi-
cines into these tiny blood vessels more difficult. This also
slows the transport of the medicines from these minute
blood vessels to larger blood vessels and then to their target
organs. This would be an impairment of absorption in
topically applied medicines like patches in older persons.
Here is another factor that further complicates absorption of
various substances in older skin.
Alterations in Inflammation and Irritation
— Older individuals are less able to fight infections.
For this reason, the number of viral infections (colds
or shingles as examples) is increased in older persons.
The severity of infections also tends to be greater with
age. We recommend that older persons are vaccinated against
the flu because their mortality is higher if they contract
the illness. Immunity is decreased in the skin as well
as other tissues with aging. Also, it has been shown that
both irritant responses and allergic inflammatory responses
are less in older skin. This is probably related to impaired
function of immune cells and also decreased production
of inflammatory proteins neces- sary to mount an inflammatory
or immune response.
Except for the few areas mentioned in the above discussion
for which clear evidence exists, a true consensus of the
changing function of skin elements with age and its effect
upon the body as a whole awaits further investigation.
There is still much to be discovered in this area.
Limiting the Effects of Aging — In order
to delay the changes seen with aging and photodamage,
several tenets may be simply stated and will be amplified
in other chapters. Limit intrinsic oxidative stress—and
included here is also providing extra antioxidant protection.
Limit photodamage. Avoid tobacco use. Control other diseases
that, if unchecked, will further oxidative damage--particularly
control vascular disease and diseases associated with
vascular disease, such as diabetes.
 References
“Percutaneous Absorption and
Inflammation in Aged Skin: A Review”,
J.
Harvell, H. Maibach; J Amer Acad Derm; Dec 1994; 1015-1021.
“Towards Obsolete Senescence”,
F Henry, N Claessens, O Martalo,
AL Fraiture, C Peirard-Franchimont, GE Pierard; Rev Med
Liege; 2000 Feb; 555(2):110-3.
The Biology of the Skin;
RK Freinkel, DT Woodley, eds;
Parthenon Publish- ing: New York, London; 2001.
Physiology of the Skin;
PT Pugliese, Allured Publishing:
Carol Stream, Illinois, USA; 1996. |
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