THE SCIENCE OF AGING & ANTIOXIDANTS

modern scientifically sound skincare to their clients seriously.

anti-oxidants, actives like niacinamide, CoQ10, Vitamins A, E and Ester C,
panthenol, grape seed extract, and organic Black tea are the highlights of their fully
loaded arsenal for skin protection and regeneration.
And what good are anti-oxidants slathered on the skin, anyway? For this post, let’s
focus on the basics of oxidation, and the role of anti-oxidants. We can do a deep
dive into inflammation next time around.
reactive oxygen species, also called ROS or “free radicals”ROS can damage all
cellular components from nuclear DNA to cell membranes and everything in
between. The damage caused by ROS leads to a state of chronic inflammation
which is a proved causative factor in the aging process.
There are several naturally occurring enzymatically based antioxidant systems,
each capable of neutralizing ROS. Oxidative stress occurs when the endogenous
ability to cope with ROS is exceeded and is considered a causative factor in nearly
all conditions and diseases associated with aging. This is particularly true of
photoaging and cancer of the skin.
The major endogenous antioxidants are superoxide dismutase, catalase, and
glutathione peroxidase. The levels and composition of endogenous antioxidant
molecules differ from tissue to tissue and by cell type. It is possible to overwhelm
the body’s antioxidant capability, especially if environmental factors (sun
exposure, smoke, toxins, etc.) are substantial. Changes during aging also contribute
to the decline in endogenous antioxidant defenses.Vitamins C and E are thought to
protect the body against the destructive effects of free radicals by donating one of
their own electrons, thus ending the electron-“stealing” reaction. The antioxidant

nutrients themselves don’t become free radicals by donating an electron because

they are stable in either form. Instead, they act as scavengers, helping to prevent
cell and tissue damage that could lead to cellular damage and disease.
Vitamin E is the most abundant fat-soluble antioxidant in the body and one of
the most efficient chain-breaking antioxidants available. It is the primary defender
against oxidation. Primary defender against lipid peroxidation (creation of unstable
molecules containing more oxygen than is usual).
Vitamin C is the most abundant water-soluble antioxidant in the body and acts
primarily in cellular fluid. It is of particular value in combating free-radical
formation caused by pollution and cigarette smoke.
Other antioxidants of potential value are selenium, zinc, silymarin, soy
isoflavones, and tea polyphenols. Their topical use may favorably supplement
sunscreen protection and provide additional anticarcinogenic protection.
Cytokines are chemical signals produced by all cells that modulate inflammation.
Growth factors are a type of cytokine or signaling molecule that leads to tissue
growth, whether for purposes or development (e.g. embryogenesis) or healing
(regeneration). A damaged tissue needs to be rebuilt. But rebuilding cannot occur
in the presence of inflammation – newly minted cells just get gobbled up along
with the old & dying cells. Thus, in a wise conservation strategy, inflammatory
cytokines tend to depress levels of growth factors while anti-inflammatory
cytokines tend to increase their activity.
Reactive Oxygen Species (ROS) are released during inflammation, which cause
both oxidative damage and elicit the release of additional inflammaging
cytokines. This may lead to a vicious cycle, accumulating over decades, whereby
the persistently pro- inflammatory state leads to pathophysiological changes in the
tissue and a vicious cycle of inflammation, an immune “healing” response in
response, and the “aging” of the tissue as evidenced by fibrosis, scarring,
degeneration, and e.g. (skin being the most visible) things like wrinkles and
discoloration, skin laxity, or possibly cancers and other lesions related to chronic
oxidative stress.
magic of stem cells. Human stem cells, not fruity ones (which are rather beside the
point since their cytokines are indecipherable by human cells).
Plant derived isoflavones are therefore useful in topical applications to obtain
estrogenic effects
Actives may benefit dermal collagen through protective effects (principally
antioxidant defense) against deleterious assaults from sun or toxin (e.g. tobacco)
exposure, or through stimulation of collagen synthesis per se. There is scant
research that supports the ability to preferentially stimulate the synthesis of Type
III collagen over Type I.

Niacinamide (Vitamin B3)

Increased production of collagen based on in vitro measurements, and decreased
production of excess dermal glycoaminoglycans.
Retinoids (Vitamin A)
Vitamin A analogs comprise the retinoids and topical application has been shown
to be effective in stimulating more rapid cellular turnover in the skin, and to
promote synthesis of pro-collagen. (Please see the BFT posting on vitamin A.)
Vitamins C and E
Because free radicals are a major culprit behind UVA-induced skin alterations,
application of topical antioxidants would thus seem beneficial and studies confirm
their efficacy. One study found that pro-oxidative factors that accelerate skin aging
might activate a self-maintained micro-inflammatory process that interferes with
skin elasticity and thickness Double-blind studies of topical application of blended
aqueous and lipid borne vitamin C compounds showed decreased photoaging
scores and increased collagen (Type I) synthesis. Vitamin C demonstrates
protective effect against UVA radiation with addition of topical vitamin E showing
combined protective antioxidant effect from UVB exposure.
Peptides & Cu++Peptides
KTTKS (a pentapeptide) is itself a fragment of dermal collagen, and stimulates
collagen production in fibroblast cultures. At very low levels in culture, KTTKS
reduces excess dermal GAG’s. GHK is a tripeptide fragment of collagen. Copper is
a required cofactor for activity of lysyl oxidase, an enzyme involved in collagen
synthesis. The complex of copper and a peptide (tri or penta) has been examined
extensively in the wound healing literature, and shown to be effective at
stimulating collagen as well as specific matrix remodeling MMP’s (matrix
metalloproteinases). The specific mechanisms have been investigated at a deeper
level and found to include induction of cytokines including FGF (fibroblast growth
factor) and specifically the beta-3 version as opposed to beta-1. The latter
contributes to scarring during healing, while the former has the opposite effect.
A double-blind, placebo-controlled, split-face, left–right randomized clinical study
assessing two topical products: moisturizer control product vs. the same
moisturizer product containing 3 ppm palmitoyl pentapeptide was well tolerated
and provided significant improvement vs. placebo control for reduction in
wrinkles/fine lines by both quantitative technical and expert grader image analysis.
The National Institutes of Health carried out a rstudy and found pentapeptides
increases production of collagen in sun-damaged skin. Subsequent studies have
shown when pentapeptides are topically applied; it can stimulate the production of
collagen and diminishes wrinkles and lines.
Decorin, a naturally occurring small cellular or pericellular matrix proteoglycan, is
a component of connective tissue, binds to type I collagen fibrils, and plays a role
cin ollagen fibrillogenesis, regulating excessive bundle-like aggregation of
collagen. As skin ages, there is lack of functional decorin, which results in
disrupted collagen fibres and in a reduction in the tensile strength of the skin. Two
tetrapeptide sequences have been identified as the specific binding sites of decorin
to collagen fibrils. These sequences were engineered to generate new tetrapeptides
with improved affinity that would present a decorin-like activity. The candidates
were screened with an in vitro collagen fibrillogenesis assay and the tetrapeptide
with International Nomenclature of Cosmetic Ingredients (INCI) name Tripeptide-
10 Citrulline achieved the best results. Like decorin, this synthetic tetrapeptide
proved, through in vitro tests, to regulate collagen fibrillogenesis and to influence
the diameter of collagen fibres, making them thinner and more uniform. .
Palmitoyl Tetrapeptide-7 is a synthetic peptide comprised of four amino acids
whose sequence is SSNA. Palmitic acid is attached to the peptide chain as a
penetration enhancer to drive the peptide through the stratum corneum. PT-7 was
formulated with the goal of suppressing the body’s production of excess
interleukins, cytokines which trigger the body’s acute inflammatory response
which leads to glycation damage. Remember, there are good cytokines and bad
cytokines when it comes to scar free healing, and rejuvenation.
Coenzyme Q10 ( Nano-Lipobelle H EQ10 / Idebenone)
Coenzyme Q10 is a potent antioxidant able to penetrate into the viable layers of the
epidermis and reduce the level of oxidation from UVA radiation. CoQ10 is also
able to significantly suppress the expression of collagenase in human dermal
fibroblasts following UVA irradiation. These results indicate that CoQ10 has the
efficacy to prevent many of the detrimental effects of photoaging. Nano-Lipobelle
H EQ10 is an enhanced penetrating modification based on liposome technology
and Idebenone is a synthetic analog.
Phytessence Wakame (Japanese sea kelp)
This Japanese sea kelp contains an inhibitor of hyaluronidase, the enzyme that
breaks down hyaluronic acid, and hence is protective of hyaluronic acid. The fetal
wound matrix, which in contrast to adult skin, does not scar during healing, is rich
in hyaluronic acid. In addition, topical hyaluronic acid has been associated
experimentally with a reduced amount of scarring in postnatal wound
healing. Hyaluronic acid extracted from human skin and scar tissue is associated
with collagen and other proteins. In protecting hyaluronic acid from hyaluronidase,
collagen scaffolding may be prevented from damage.
Topical estradiol and soy isoflavones
Collagen, elastin and dermal hyaluronic acid appear sensitive to and dependent
on hormonal levels as hormone reduction produces skin dryness and losses in
elasticity and volume. Some studies show woman’s skin can lose up to 1/3 of its
collagen within five years of menopause. Because of possible systemic effects
including increased risks of breast cancer, cardiovascular and
thromboemboembolic disease, topical hormone application, rather than systemic
administration, is recommended when skin effects are specifically targeted. .
Evidence also suggests estrogens are stronger antioxidants than Vitamin
C and E and that female face and chest skin are especially estrogen-receptive.
Estrogen normally works by signaling genes in cells to be switched on or off,
however one recent study has found that sun-damaged skin isn’t improved by
topical estradiol(Topical 17-beta estradiol in ethanol/propylene glycol (ETOH/PG).
Because photo-aging is superimposed on natural aging in sun-exposed areas of the
skin, the results suggest that alterations induced by long-term sun exposure hinder
the ability of topical estradiol to stimulate collagen production in aged human skin.
Soy beans are rich in phytoestrogens that function as selective estrogen receptor
modulators producing physiologic responses similar to natural estrogens. Plant
derived isoflavones are therefore useful in topical applications to obtain estrogenic
effects yet not so well absorbed as to pose a risk to male useage.

Photolyase CPD and Phycocyanin

Phystoestrogens are plant derived compounds that mimic estrogen effects and are
common in oil seeds, nuts, soy, flax and other botanical sources. One class of

phytoestrogens are the isoflavones which are derived from soy beans. Soy
isoflavones have demonstrated efficacy in replacing estrogenic effect in skin when
applied topically with beneficial effect on stimulation of fibroblast proliferation,
reduction of collagen breakdown, and inhibition of 5α-reductase. The prevalent
isoflavone in soy is the glycoside genistin. Its aglycone (the molecular form
without sugar residues), genistein, is a well-known inhibitor of protein tyrosine
kinase, critical enzymes involved in the molecular mechanisms that link UV
exposure to photoaging. Soy derived isoflavones are helpful organic and natural
topical “replacements” for declining estrogen levels.

Essential Fatty Acids: Body cannot produce on it's own. 2

types: Omega 3-fish & chia=anti-inflamatory prop., Omega 6-
corn & soybean oil- pro-inflamatory properties.
EFAs also help to reduce inflammation, which can lead to a
variety of skin problems, and play a role in cell regeneration
- keeping skin looking young and radiant. Fatty acids are a
type of lipid which are essential for maintaining the integrity
of cell membranes in the outermost layer of your skin. Both
omega-3 and omega-6 fatty acids are important for keeping
your skin barrier moisturised. Without enough essential fatty
acids, the skin can become dry, flaky, and prone to irritation.
Anti-Aging
There are multiple approaches to anti-aging skin care and ingredients To Die
For offers a variety of ingredients that deliver a more youthful appearance
through different pathways: Wrinkle Prevention or Improvement for refined
skin texture, Enhanced Collagen and Elasticity for firmer and tightened skin,
or through Enhanced Moisturization and Hydration for a youthful glow. Anti-
Aging ingredients can have a significant impact on the appearance, and
progression, of mature skin, especially when the product, that you add them
to, offers an effective delivery system to get the actives to spread smoothly
across the surface of the skin and maintain stability while on the skin.
Moisturizers / Hydrators
Moisturizers / Hydrators are ingredients that counteract dryness in skin and
hair care. These materials are often humectants (substances which draw
moisture from the air and bring it closer to the skin or hair). Some are what
we call “moisture binders” because they force cells to hold water, and
therefore retain moisture. Some are what we call “film formers” because
they form a breathable, protective barrier on the skin, reducing “TEWL”
(TransEpidermal Water Loss). TEWL is the migration of moisture upward
from deeper dermal tissues where it is lost to evaporation after passing
through the stratum corneum. TDF carries the most effective moisturizers
known, allowing you to develop the most efficacious products on the market
today.

Anti Irritant
Our Anti irritant category of ingredients is for those that have shown, in
vivo, improvement in the structure of the skin after exposure to common
irritants such as: sulfates, citrals .... Because of this activity they are known
to soothe the skin.

Acids
Often called Fruit Acids, Alpha Hydroxy Acids (AHAs) and Beta Hydroxy
Acids (BHAs) are some of the most well-researched and effective
ingredients in personal care today. Alpha Hydroxy Acids at concentrations of
2% or less, Alpha Hydroxy Acids (AHAs) are extremely effective
moisturizers, having powerful moisture-binding properties. Alpha Hydroxy
Acids at concentrations of 3-70%, Alpha Hydroxy Acids are the most
effective exfoliants known, increasing cell proliferation to reveal a fresh,
young, beautiful layer of skin. Beta Hydroxy Acids at concentrations of 2%
or less, Beta Hydroxy Acids (BHAs) are are powerful anti-inflammatories,
and are also efficacious in prevention and treatment of acne due to their
pore cleansing and antibacterial functions. Beta Hydroxy Acids at
concentrations of 3-60%, Beta Hydroxy Acids are used to combat the visible
signs of aging, and as a chemical exfoliant for young or acne-prone skin.

Alpha Hydroxy Acids

All Ingredients To Die For Alpha Hydroxy Acids (AHA's) are from
plant source.Alpha Hydroxy Acids (AHA's) at concentrations of 2% or
less are extremely effective moisturizers, having powerful moisture-binding
properties. When used above 2% and with a final pH under 4.0 the Alpha
Hydroxy Acids (AHA's) are one the most effective exfoliants known,
increasing cell proliferation and shedding to reveal a fresh, young, beautiful
layer of skin.The most commonly utilized Alpha Hydroxy Acids (AHA's) in
cosmetics are Citric, Glycolic, and Lactic. Of these, we never recommend the
use of Citric Acid in skin care due to it's potential for irritation. We only
recommend the use of Citric Acid in fizzing bath products and then only
because the pH is controlled, and neutral, due to the combination with
baking soda which lessens potential for irritation.For the most powerful
exfoliation activity the most commonly used is Glycolic Acid due to it's
smaller size which enables the Glycolic Acid to easily penetrate the pores for
a much more effective, but aggressive, sloughing of dull surface skin.For the
most gentle exfoliation we recommend Lactic Acid which is much less
aggressive but still an effective exfoliator. In most AHA products a
combination is utilized to get the best of all activities to offer exfoliation
while taming irritation.

Beta Hydroxy Acids

Beta Hydroxy Acids (BHAs) at concentrations of 2% or less, Beta
Hydroxy Acids (BHAs) are are powerful anti-inflammatories, and are also
efficacious in prevention and treatment of acne due to their pore cleansing
and antibacterial functions. Beta Hydroxy Acids at concentrations of 3-60%,
Beta Hydroxy Acids are used to combat the visible signs of aging, and as a
chemical exfoliant for young or acne-prone skin.