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<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong><br />

& <strong>Texture</strong><br />

<strong>Research</strong> <strong>Update</strong>


contents<br />

The State of Anti-Aging<br />

Skin Care<br />

1 Skin care science advances as<br />

market proliferation and consumer<br />

confusion increases<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong><br />

& <strong>Texture</strong> Infl uence<br />

Self-Perception<br />

2 How fi ne lines, wrinkles and<br />

texture contribute to perceptions<br />

of age<br />

Biology of <strong>Fine</strong> <strong>Lines</strong>,<br />

<strong>Wrinkles</strong> & <strong>Texture</strong><br />

3 Defi ning the Problem<br />

Where a fi ne line ends and a<br />

wrinkle begins<br />

4 Targeting the Problem Where<br />

it Occurs<br />

The common facial areas where<br />

problems appear<br />

4 Intrinsic & Extrinsic Factors<br />

Associated with Skin Aging<br />

The skin’s responses to biological<br />

aging and environmental exposures<br />

6 The Fundamentals of<br />

Preventing and Reversing<br />

the Signs of Skin Aging<br />

Talking points on how to minimize<br />

wrinkles and strengthen skin<br />

Innovations in<br />

Technology &<br />

Clinical Testing<br />

6 Advances in Molecular Testing<br />

From genomics to metabolomics<br />

and beyond<br />

7 Advances in Preclinical and<br />

Clinical Testing<br />

A new age of safety and effi cacy<br />

testing<br />

Addressing <strong>Fine</strong> <strong>Lines</strong>,<br />

<strong>Wrinkles</strong> & <strong>Texture</strong><br />

Changes<br />

10 Topical Anti-Aging Compounds<br />

A table of some of the most<br />

researched and popular skin care<br />

compounds<br />

11 What Works<br />

The latest research on antioxidants<br />

and UV protection, retinoids, niacinamide<br />

and peptides<br />

Infl ammatory Responses<br />

& Their Relationship<br />

to Skin<br />

16 Putting the Pieces Together:<br />

Genomics, Infl ammation and<br />

Skin Aging<br />

Infl ammatory pathways and their<br />

effects on skin aging


The State of Anti-Aging Skin Care<br />

The appearance of fi ne lines and wrinkles is one of the most<br />

common signs of aging in people around the world. Yet, regardless<br />

of when wrinkles are fi rst noticed, they are an unwelcome<br />

indicator of age, especially for women who are leading more<br />

active lives and are looking for ways to look and feel their best.<br />

Increased life expectancy has changed the concept of aging and,<br />

in turn, propelled anti-aging research that has led to a multitude of<br />

topical applications. Skin science is advancing at an exponential<br />

pace, yet profound gaps remain in patients’ understanding of the<br />

biological mechanisms of skin and the research supporting interventions<br />

that can help to preserve supple, smooth, youthful skin<br />

and nourish, replenish and renew aging skin.<br />

Amid the proliferation of specialty<br />

anti-aging products and the<br />

ensuing consumer confusion, the<br />

anti-aging fi eld is booming with<br />

discoveries made possible through<br />

the application of complex science<br />

and advanced technologies including<br />

the gene chip, sophisticated<br />

medical imaging tools and computational<br />

models. With a focus on<br />

the physical and molecular basis<br />

of fi ne lines, wrinkles and poor<br />

texture, P&G <strong>Beauty</strong> scientists have<br />

brought exacting precision to this<br />

area of dermatological study and<br />

have translated their knowledge to<br />

drive the identifi cation of improved<br />

anti-aging ingredients.<br />

As scientists continue to search for<br />

breakthroughs, deeper analyses of<br />

bio logical pathways that distinguish<br />

young and aging skin are providing<br />

new insights into the processes of<br />

skin aging which will in turn lead to<br />

better preventive measures and antiaging<br />

treatments.<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 1


<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong><br />

& <strong>Texture</strong> Infl uence<br />

Self-Perception<br />

Th roughout the evolution of skin<br />

care, fi ne lines, wrinkles and texture<br />

have been persistent concerns for<br />

aging women. <strong>Research</strong> reveals that<br />

this concern is legitimate and related<br />

to self-image and age-related discrimination.<br />

Poor self-image is associated<br />

with chronic illness and fewer<br />

preventive health behaviors, such as<br />

exercise, 1 and aged skin, particularly<br />

in women, has also been linked to<br />

job discrimination. 1 Such far-reaching<br />

psycho-social implications help<br />

explain the ongoing quest to develop<br />

better treatments to conceal and<br />

delay the signs of aging.<br />

As this quest has progressed, skin care<br />

formulators have sought to use the<br />

best science available to address fi ne<br />

lines, wrinkles and texture problems.<br />

As illustrated in the timeline below, a<br />

snapshot of trends over past decades<br />

Decades of Skin Care<br />

1960s<br />

Moisturization is<br />

key to wrinkle reduction<br />

(e.g., propylene<br />

glycol, lactate)<br />

2 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

1970s<br />

Super-moisturization<br />

ingredients debut<br />

(e.g., glycerol,<br />

petrolatum)<br />

demonstrates that the approaches to<br />

addressing the problem have evolved<br />

in step with technological advances<br />

and a wider availability of ingredients.<br />

In tandem with the increased availability<br />

of specialty creams and lotions,<br />

consumers have become more aware<br />

of and concerned with the multitude<br />

of factors relating to aging skin.<br />

<strong>Research</strong>ers have found there are<br />

seven key signs of aging that concern<br />

women and these concerns are consistently<br />

identifi ed, regardless of their<br />

diverse lifestyles and ethnicities.<br />

P&G <strong>Beauty</strong> conducted surveys with<br />

over 6,000 women across three continents<br />

and found the following concerns<br />

to be consistently identifi ed:<br />

• <strong>Fine</strong> lines and wrinkles<br />

• Skin texture<br />

• Skin tone<br />

• Skin surface dullness<br />

• Visible pores<br />

• Blotchiness and age spots<br />

• Dryness<br />

1980s<br />

Exfoliation is the rage<br />

(e.g., hydroxy acids)<br />

While this longer list of concerns<br />

suggests that women are increasingly<br />

taking a more holistic view of the<br />

signs of skin’s aging, fi ne lines and<br />

wrinkles continue to be a prime concern<br />

for women. As one of the fi rst<br />

visible manifestations of aging in a<br />

world that values youthful appearances,<br />

there are no indications that<br />

the focus on fi ne lines and wrinkles<br />

will wane. But how much do wrinkles<br />

and fi ne lines contribute to selfperceptions<br />

compared to these other<br />

age-related factors?<br />

To better understand the relative contribution<br />

of fi ne lines and wrinkles<br />

versus skin color unevenness on selfperceptions,<br />

P&G <strong>Beauty</strong> researchers<br />

conducted a study to isolate the<br />

role that fi ne lines and wrinkles play.<br />

In the study, researchers took digital<br />

facial images of subjects 40 years or<br />

older using a custom high-resolution<br />

digital imaging system. Th ese images<br />

were then subjected to the digital<br />

removal of fi ne lines, wrinkles and<br />

color unevenness. Finally, groups of<br />

1990s<br />

Age-defying ingredients<br />

make news<br />

(e.g., retinoids)<br />

2000s<br />

An ever-expanding<br />

range of specialty<br />

ingredients leads to<br />

better products, but<br />

also consumer confusion<br />

(e.g., niacinamide,<br />

peptides)


panelists were asked to identify the<br />

age of the images they were shown.<br />

Preliminary fi ndings reveal that fi ne<br />

lines and wrinkles are the primary<br />

factors impacting perceptions of<br />

female facial age. Th ese early fi ndings<br />

underscore the need for further<br />

research to elucidate the connection<br />

between skin aging and perceptions,<br />

and reinforce eff orts to discover better<br />

and more accessible anti-aging<br />

solutions.<br />

Biology of <strong>Fine</strong><br />

<strong>Lines</strong>, <strong>Wrinkles</strong><br />

& <strong>Texture</strong><br />

In looking at the biological mechanisms<br />

which lead to fi ne lines,<br />

wrinkles and changing texture, it is<br />

important to start with clear working<br />

defi nitions of these phenomena. Th is<br />

is especially important because they<br />

often overlap, the progression from<br />

one to the other is subtle and the<br />

measurements used to evaluate them<br />

vary across the fi eld of dermatology.<br />

Adding to this complexity, one must<br />

take into account that these phenomena<br />

are driven by both intrinsic and<br />

extrinsic factors and that these factors<br />

are highly interrelated. As science<br />

unravels each nuance of these processes,<br />

better strategies for addressing<br />

the undesirable eff ects of skin aging<br />

are emerging, and P&G <strong>Beauty</strong> sci-<br />

entists and their collaborators are<br />

constantly seeking new insights that<br />

will ultimately lead to improved antiaging<br />

treatments.<br />

Defi ning the Problem<br />

Across dermatological literature,<br />

there are various synonyms and characteristics<br />

used to describe fi ne lines,<br />

wrinkles and inconsistent texture,<br />

and consequently, defi nitions have<br />

been somewhat broad and expansive.<br />

In their work, P&G <strong>Beauty</strong> researchers<br />

utilize the criteria below to defi ne<br />

fi ne lines, wrinkles and inconsistent<br />

texture:<br />

Surface <strong>Wrinkles</strong>/<strong>Fine</strong> <strong>Lines</strong><br />

• Crevices in the surface of the skin<br />

that only delve into the epidermal<br />

layer<br />

• Less than 0.1mm in depth<br />

Wrinkle<br />

Fold<br />

Line<br />

• May either disappear upon relaxation<br />

or be barely discernible<br />

• Th ought to be reducible/eliminated<br />

without the use of invasive<br />

procedures<br />

Deep <strong>Wrinkles</strong>/Folds<br />

• Crevices in the skin surface that<br />

delve into the dermal layer (deep<br />

wrinkles) and even into the subcutaneous<br />

layer (folds)<br />

• Greater than 0.1mm in depth, up<br />

to 0.4mm in depth<br />

• Remain well-defi ned and evident<br />

upon the relaxation of the muscles<br />

and the skin<br />

Inconsistent <strong>Texture</strong><br />

• Enlarged pore size<br />

• “Bumpy” texture<br />

• Rough or fl aky texture<br />

Epidermis<br />

Dermis<br />

Subcutis<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 3


Targeting the Problem<br />

Where It Occurs<br />

Experts agree that wrinkles usually<br />

begin as fi ne lines. Generally, these<br />

lines are found in the areas used most<br />

frequently in facial expressions and<br />

those highly exposed to UV rays.<br />

As a result, wrinkles are commonly<br />

found in the areas pictured below.<br />

Additionally, inconsistent skin texture<br />

can be found on many areas<br />

of the face, most noticeably on the<br />

nose and cheek area (“bumpy” texture,<br />

enlarged pores) and the area<br />

between the eye and the ear. Other<br />

texture problems that can be found<br />

across the entire face are rough or<br />

fl aky texture and scarring or pitting<br />

from acne.<br />

Forehead<br />

Crows feet<br />

Enlarged<br />

pores<br />

Upper & lower lip<br />

Chin/underside of chin<br />

4 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

Intrinsic & Extrinsic Factors<br />

Associated with Skin Aging<br />

A large body of research has helped to<br />

delineate intrinsic and extrinsic factors<br />

at work in aging skin. Th e process of<br />

intrinsic skin aging follows a similar<br />

trajectory as that of most internal<br />

organs, with factors including inevitable<br />

changes in hormone levels, particularly<br />

estrogen, as well as declines<br />

in metabolic activity and cell regeneration.<br />

2 Extrinsic skin aging is caused<br />

primarily by UV exposure; 3 however,<br />

exposure to environmental pollution<br />

and smoking are also signifi cant factors.<br />

Yet, while science has, for research<br />

purposes, categorized age-inducing<br />

factors as either intrinsic or extrinsic,<br />

increasing evidence demonstrates their<br />

interdependencies; specifi cally, we are<br />

Bumpy texture<br />

Laughter lines<br />

Corners of mouth<br />

In addition to the problem areas shown above, rough or fl aky texture can appear anywhere<br />

on the face.<br />

Skin Facts<br />

• Up to approximately mid-30s, the<br />

skin epidermis renews itself every<br />

4-6 weeks. As the body ages, the<br />

renewal time slows to about 6-8<br />

weeks.<br />

• The skin of an average woman<br />

weighs about 3 kg, and that of an<br />

average man approximately 5 kg.<br />

• The thickness of the skin varies,<br />

depending on its site on the body. It<br />

is thinnest on the eyelids and thickest<br />

on the palms of the hands and<br />

the soles of the feet.<br />

learning more about the ways extrinsic<br />

factors accelerate intrinsic aging.<br />

One example of the complex interplay<br />

of factors involves free radicals,<br />

which are both generated internally<br />

through normal metabolic processes<br />

and produced as a consequence of<br />

external factors, including UV exposure.<br />

As a result of the age-associated<br />

decline in protective internal antioxidant<br />

mechanisms, free radicals<br />

accumulate in the body and alter<br />

both the proteins and the DNA<br />

in the skin. In fact, according to a<br />

recent study published in Nature, 4<br />

the buildup of damaged DNA drives<br />

the aging process. In addition, ongoing<br />

accumulation of internally-generated<br />

free radicals combined with<br />

those generated from UV and other


external assaults (surfactants, allergens,<br />

and other irritants) can promote<br />

a chronic infl ammatory state.<br />

Th is chronic infl ammatory state<br />

compromises skin health and accelerates<br />

the aging process; for example,<br />

proteolytic enzymes are produced,<br />

resulting in collagen degradation. 5<br />

Other changes resulting from the<br />

complex interplay between intrinsic<br />

and extrinsic factors that impact the<br />

appearance of fi ne lines, wrinkles and<br />

texture include the following:<br />

• Th ickness of the epidermis, cellular<br />

turnover rate of both the epider mis<br />

and the stratum corneum declines<br />

and epidermal diff erentiation is<br />

6, 7 altered.<br />

• Dermis becomes thinner as major<br />

structural molecules including collagen,<br />

elastin and glycosaminoglycans<br />

decrease in amount. 8, 9, 10 Metalloproteinase<br />

activity also decreases<br />

in photodamaged skin and the<br />

structure of these molecules<br />

becomes disorganized and cross-<br />

11, 12, 13, 14, 15<br />

linked.<br />

• Convolution of dermal-epidermal<br />

junction (Rete ridges) fl attens with<br />

age, resulting in a loss of mechanical<br />

strength. 16 Th is also leads to<br />

decreased microcirculation to the<br />

upper dermis and, thus, decreased<br />

nourishment to the epidermis.<br />

• Age-related changes in inter- and<br />

intra-cellular signaling lead to<br />

17, 18<br />

decreases in collagen synthesis.<br />

• Changes in hyaluronic acid content<br />

within the skin varies with<br />

age. Hyaluronic acid is a natural<br />

moisturizer within the skin binding<br />

up to 1000 times its weight in<br />

water. Age-related declines result<br />

in compromised moisturization<br />

19, 20<br />

and fi rmness.<br />

• Decrease in intracellular energy<br />

sources including ATP and NADH<br />

lead to an inability of skin cells to<br />

sustain youthful skin biochemistry,<br />

thereby reducing the skin’s ability<br />

to maintain and restore youthful<br />

skin structure. 21<br />

Th ese changes work together to compromise<br />

skin’s elasticity, fi rmness and<br />

structure, which contributes to areas<br />

of collapse and irregularity and ultimately<br />

manifests as fi ne lines, wrinkles<br />

and texture problems.<br />

As P&G <strong>Beauty</strong> scientists continue<br />

to study how these processes contribute<br />

to fi ne lines, wrinkles and<br />

texture changes, they’re also seeking<br />

to better understand what processes<br />

impact other consumer-relevant signs<br />

of aging, including skin tone, surface<br />

dullness, pore size, blotchiness, age<br />

spots and dryness. Th e intention of this<br />

ongoing research is to develop antiaging<br />

products that can comprehensively<br />

approach the many factors that<br />

lead to the appearance of aging skin.<br />

Innovations in<br />

Technology &<br />

Clinical Testing<br />

With our advancing understanding<br />

of the biology of fi ne lines and<br />

wrinkles comes the application of<br />

more sophisticated technologies and<br />

more rigorous research methods to<br />

measure the eff ects of topical treatments.<br />

Gone are the days of trial<br />

and error, when the effi cacy of topical<br />

interventions was determined by<br />

treating symptoms without a clear<br />

sense of the underlying biological<br />

mechanisms. Now, researchers are<br />

utilizing a host of complex sciences<br />

and technologies to understand these<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 5


mechanisms, and designing their<br />

studies to eliminate the uncertainties<br />

and subjectivity that colored earlier<br />

conclusions.<br />

Advances in Molecular Testing<br />

At the molecular level, P&G <strong>Beauty</strong><br />

researchers are bringing to bear several<br />

complex sciences to gain a more<br />

complete picture of skin aging. Th ese<br />

sciences include:<br />

• Genomics: a branch of biotechnology<br />

which applies genetic and<br />

molecular biology techniques to<br />

the genetic mapping and DNA<br />

sequencing of sets of genes or<br />

the complete genomes of selected<br />

organisms.<br />

• <strong>Wrinkles</strong> and poor texture are among the earliest signs of aging.<br />

Over time, the skin becomes thinner, drier and less elastic. The<br />

timing and severity of the appearance of fi ne lines and wrinkles<br />

is due to:<br />

– Your genetic predisposition to wrinkles and the natural aging<br />

process<br />

– Exposure to sunlight and other environmental irritants, including<br />

pollution<br />

• Overexposure to the sun is the main culprit of premature agerelated<br />

changes, including wrinkles, roughness, altered pigmentation,<br />

loss of skin tone and dilated blood vessels. To protect<br />

your skin, use a daily moisturizer with broad spectrum SPF 15<br />

sunscreen included. If you plan to be outside, apply and reapply<br />

sunscreen and don’t forget to wear a hat, protective clothing<br />

and sunglasses. Try to limit your exposure to the sun during the<br />

middle of the day when UV light is at its strongest.<br />

6 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

• Proteomics: a branch of biotechnology<br />

which applies the techniques<br />

of molecular biology,<br />

bio chemistry and genetics to analyzing<br />

the structure, function and<br />

interactions of the proteins produced<br />

by the genes of a particular<br />

cell, tissue or organism.<br />

• Metabolomics: the systematic study<br />

of the unique chemical fi nger prints<br />

that specifi c cellular processes leave<br />

behind; specifi cally, the study of<br />

their small-molecule metabolite<br />

profi le.<br />

• Bioinformatics: the use of techniques<br />

including applied mathematics,<br />

infor ma tics, statistics,<br />

The Fundamentals of Preventing & Reversing the Signs of Aging Skin<br />

com puter science, artifi cial intelligence,<br />

chemistry and biochemistry<br />

to solve biological problems, usually<br />

on the molecular level.<br />

Of these applied disciplines, one<br />

of the most exciting areas of P&G<br />

<strong>Beauty</strong> research is genomics, where<br />

the sequencing of the human genome<br />

has given scientists an exponentially<br />

larger toolbox from which to learn<br />

and innovate targeted interventions.<br />

Owing directly to the breakthroughs<br />

of modern genetics, researchers now<br />

have the ability to identify the specifi<br />

c human genes that are modulated<br />

in response to various stimuli.<br />

• Supplement the protective effects of broad spectrum<br />

SPF 15 coverage with anti-aging treatments that can help<br />

strengthen the skin, including the skin barrier, and reverse<br />

the signs of aging. These include topical antioxidants, niacinamide,<br />

N-acetyl glucosamine (NAG) and peptides, among others.<br />

• Quit smoking or don’t start. Cigarette smoke causes marked<br />

decreases in the antioxidant capacity of skin and production of<br />

new collagen.<br />

• Exercise regularly to help fl ush impurities out of your skin. Exercising<br />

also facilitates the production of sebum, which is the skin’s<br />

natural moisturizer, and improves blood fl ow to the skin.<br />

• Optimize your immune function and skin’s natural self-repair<br />

mechanisms by drinking plenty of water, eating a well-balanced<br />

diet and getting plenty of rest.


Gene Chip Technology<br />

One new technology that has been<br />

developed as an outgrowth of the<br />

sequencing of the human genome is<br />

a gene-monitoring device known as<br />

the gene chip. Th e gene chip’s versatile<br />

technology has led to it being<br />

used by researchers studying various<br />

diseases including autism, bipolar<br />

disease, cancer, diabetes and heart<br />

disease. In addition to these applications,<br />

the gene chip technology is<br />

enabling P&G <strong>Beauty</strong> researchers to<br />

understand the underlying biological<br />

basis of changes seen on the skin surface,<br />

including changes in fi ne lines<br />

and wrinkles.<br />

Th e chip itself has indicators that represent<br />

genes comprising the human<br />

genome. By placing fragments of<br />

Tiled onto an Affymetrix gene chip are oligonucleatide<br />

probes representing over 35,000 genes.This<br />

technology has revolutionized genomics research<br />

and is being used extensively by P&G <strong>Beauty</strong><br />

scientists.<br />

fl uorescently-tagged samples isolated<br />

from the skin onto the chip, scientists<br />

can see which genes are expressed<br />

within the sample and whether these<br />

genes are up-regulated or down-regulated,<br />

indicating specifi c molecular<br />

events contributing to a given biological<br />

process.<br />

Advances in Preclinical<br />

& Clinical Testing<br />

Along the long road from molecular<br />

to preclinical and fi nally clinical testing<br />

at P&G <strong>Beauty</strong>, ingredients and<br />

their subsequent product applications<br />

must pass clear safety and effi -<br />

cacy benchmarks before even being<br />

considered for market introduction.<br />

Beginning with testing on in vitro<br />

skin equivalents and advancing to in<br />

vivo effi cacy testing, these measurements<br />

have elevated the legitimacy of<br />

skin care science and the rigor upon<br />

which skin care claims are made.<br />

In vitro Human Skin Equivalents<br />

Th e imperative for skin product<br />

safety, combined with ethical, social<br />

and political pressures, has fostered<br />

improvements in alternatives for animal<br />

testing. One of the leading technologies<br />

that has been developed is<br />

human skin equivalent culture models.<br />

In recent years, advancements in<br />

techniques have led to cultures that<br />

mimic not only the epidermal layer<br />

but also the dermal layer, allowing<br />

these models to be used not only for<br />

safety assessments22 but also to test<br />

23, 24, 25<br />

product effi cacy.<br />

In vitro human skin equivalents reproduce many<br />

cellular and structural elements of natural skin,<br />

including the dermis, epidermis and melanocytes.<br />

Human skin equivalent cultures receive nutrients<br />

from the bottom of the culture. This facilitates<br />

application of topical ingredients, both water<br />

soluble and non-water soluble, on the top of the<br />

culture.<br />

Today’s human skin equivalents off er<br />

multiple advantages over traditional<br />

monolayer cultures:<br />

• Can be used to test undiluted<br />

materials (e.g., product formulations)<br />

which is important because<br />

not all materials are water-soluble<br />

• Are able to show cell-to-cell<br />

interaction between dermis and<br />

epidermis<br />

• Clinically relevant measures can<br />

be performed (e.g., barrier eff ects<br />

with TEWL, hydration)<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 7


Clinical Test Design<br />

In today’s era of sophisticated skin science,<br />

clinicians and consumers alike<br />

are calling for data on cosmetic products<br />

that are based on the same level of<br />

scientifi c rigor that is required of drug<br />

trials. While such trials are voluntary<br />

and require signifi cant investments in<br />

time and resources, P&G <strong>Beauty</strong> has<br />

long adhered to testing methodologies<br />

for cosmetic products that exceed<br />

those required by governmental regulatory<br />

bodies and that are relied upon<br />

by most beauty companies.<br />

Consistent with this commitment,<br />

P&G <strong>Beauty</strong> regularly conducts randomized,<br />

double-blinded clinical trials.<br />

26, 27, 28, 29, 30 Using these protocols,<br />

participants are randomly assigned<br />

to one of two or more treatment<br />

regimens, and neither the study participants<br />

nor the researchers know<br />

which participants are receiving the<br />

test therapy and which are receiving<br />

a placebo or control therapy.<br />

Th ese measures, though exhaustive,<br />

ensure potential selection biases are<br />

eliminated and that fi ndings are both<br />

objective and reproducible.<br />

Ghosting Method: Increases<br />

Accuracy of Before & After<br />

Comparisons<br />

Th e technical diffi culties involved<br />

with capturing visual data and the<br />

absence of clear digital image capture<br />

standards have resulted in many<br />

dubious before and after comparisons<br />

8 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

throughout dermatological literature.<br />

Facial expression, head position and<br />

lighting are all critical factors in determining<br />

whether a wrinkle has become<br />

smaller, larger or remained the same<br />

size and depth. Th e challenge is compounded<br />

because the more subtle the<br />

change, the more critical changes in<br />

these factors become.<br />

Given these challenges, it has taken<br />

advances in technology and scrupulous<br />

scientists to bring rigor to the<br />

process of eff ective digital imaging<br />

of aging skin. One advance that has<br />

helped solidify digital imaging as a<br />

serious documentation and measurement<br />

tool is “ghosting” technology.<br />

By replicating the original lighting<br />

and facial positioning to the most<br />

precise degree, the ghosting method<br />

helps ensure the most accurate possible<br />

assessments of skin changes,<br />

whether those changes are being<br />

determined objectively by computer<br />

image analysis or subjectively by<br />

graders or consumers.<br />

How It Works: During the subject’s<br />

initial visit, the operator captures<br />

the baseline image. At follow-up, the<br />

operator recalls the subject’s baseline<br />

image, or repositioning image,<br />

in a semi-transparent “ghost image”<br />

format.<br />

When the camera system is activated,<br />

it brings up both the baseline ghost<br />

image and an overlaid live subject<br />

Ghost image from baseline visit.<br />

Aligning the ghost and current live image.<br />

image. Th e operator aligns the baseline<br />

ghost image and overlaid live<br />

image, matching the subject’s live<br />

head position and facial expression<br />

with the baseline ghost image.<br />

Th e goal of this technological process<br />

is to minimize possible confounding<br />

variables. Not only does this help<br />

advance science by providing more<br />

precise measures, it bolsters the validity<br />

of claims and is in the best interest<br />

of consumers.


Visit 1 Visit 2<br />

Perfectly repositioned subject, even months later.<br />

FOITS Topography Maps<br />

In the world of skin science, the value<br />

of obtaining skin surface topography<br />

in vivo cannot be understated,<br />

but the data obtained is only as valuable<br />

as it is precise. In their ongoing<br />

quest for more precise measurement<br />

instruments, P&G <strong>Beauty</strong> researchers<br />

acquired a new measurement technology<br />

known as FOITS (Fast Optical<br />

In Vivo Topometry of Human Skin)<br />

to augment their existing topographical<br />

measurement system.<br />

How It Works: FOITS uses the principle<br />

of “fringe projection” to analyze<br />

the topographic features (height variations)<br />

of the skin surface. An appro-<br />

priate analogy for “fringe protection”<br />

in image capture can be made by<br />

imagining light passing through<br />

window blinds and onto an object.<br />

While stripes of light are cast onto<br />

the object, they distort the geometry<br />

of the object. But the original geometry<br />

of the object can be captured by<br />

comparing the coordinates where the<br />

light stripes meet the parallel shadow<br />

stripes. FOITS applies this same<br />

principle to skin’s topographical features.<br />

A parallel stripe pattern is fi rst<br />

projected onto the skin surface. Th e<br />

instrument then calculates the x-y-z<br />

coordinates where the original stripe<br />

pattern and the parallel dark pattern<br />

meet, generating precise data on the<br />

true skin topography.<br />

Upon acquiring FOITS, P&G <strong>Beauty</strong><br />

researchers used the technology to<br />

assess the performance of existing<br />

product lines. Th eir fi ndings were<br />

extremely satisfying — the technology<br />

itself yielded better measurements and<br />

the tested products met or exceeded<br />

study endpoints. Th is is especially<br />

Example of FOITS before and after comparison images showing the benefi ts of a test topical antiaging<br />

cream. The outer boxes contain images of wrinkles in the crow’s feet area following treatment<br />

with a test topical anti-aging cream. The inner boxes represent topographical heat maps of<br />

this same area and clearly indicate reduced fi ne lines and wrinkles.<br />

rewarding, given that the FOITS system<br />

is increasingly gaining recognition<br />

for its ability to validate product<br />

claims and that the technology has<br />

been adopted as the standard for antiaging<br />

product claims in Germany.<br />

Addressing <strong>Fine</strong><br />

<strong>Lines</strong>, <strong>Wrinkles</strong> &<br />

<strong>Texture</strong> Changes<br />

In addition to the expanded range of<br />

topical anti-aging technologies available,<br />

the variety of cosmetic procedures<br />

(e.g., face lifts, fi llers and facial<br />

peels) has multiplied in recent years.<br />

While these more invasive and costly<br />

procedures are the right decision for<br />

some, many patients prefer topical<br />

interventions, are averse to invasive<br />

procedures or fi nd them cost prohibitive.<br />

For these reasons, it is important<br />

to stay up-to-date on the latest<br />

skin care ingredients that are backed<br />

by science and can address patients’<br />

anti-aging concerns. 31<br />

Scientifi c research has substantiated<br />

the mechanism of action of several<br />

wrinkle-fi ghting ingredients. While<br />

the variety of compounds found in<br />

today’s skin care products continues<br />

to grow, not all are backed by signifi -<br />

cant clinical research. Th e table on the<br />

following page describes some of<br />

the more popular and well-researched<br />

31, 32<br />

anti-aging ingredients.<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 9


TOPICAL ANTI-AGING COMPOUNDS<br />

Ingredient/Compound Mechanism of Action<br />

Ascorbic Acid — a potent organic acid with<br />

antioxidant properties, commonly known<br />

as vitamin C. Forms of this vitamin include<br />

ascorbic acid, ascorbyl phosphate, ascorbyl<br />

palmitate and ascorbyl glucoside.<br />

CoQ10 — a naturally occurring compound<br />

found in every cell in the body that acts as<br />

an antioxidant. Also known as ubiquinone.<br />

N-acetyl Glucosamine (NAG) — a simple<br />

amino sugar and nutrient that plays a role in<br />

forming and maintaining the body’s tissues.<br />

Niacinamide — a water soluble B3 vitamin<br />

found naturally in the body. Forms of vitamin<br />

B3 that are typically used in skin care products<br />

include niacinamide (also called “nicotinamide”),<br />

nicotinic acid and nicotinate esters.<br />

Panthenol — present in all living cells and<br />

a major component of co-enzyme A, which<br />

serves a critical role in cellular metabolism.<br />

Peptides — natural or synthetic compounds<br />

containing two or more linked amino acids.<br />

Peptides that are of particular interest to the cosmetic<br />

industry include palmitoyl-lysine-threoninethreonine-lysine-serine<br />

(pal-KTTKS; Matrixyl ® )<br />

and palmitoyl-lysine threonine (pal-KT).<br />

Retinoids — derivatives of vitamin A. Retinoic<br />

acid is the functional form of vitamin A in<br />

skin and is considered to be the gold-standard<br />

Rx anti-aging treatment. Other forms of<br />

vitamin A used cosmetically include retinol,<br />

retinyl-propionate and retinaldehyde.<br />

Salicylic Acid — derivative of beta-hydroxy<br />

acid. Other forms of hydroxy acids used cosmetically<br />

include glycolic, malic, tartaric, lactic<br />

and critic acids; and polyhydroxy acids such<br />

as gluconolactone and lactobionic acid.<br />

Other Antioxidants — include alphalipoic<br />

acid, tocopherol and lutein and<br />

are employed in the cosmetic arena.<br />

Tocopherol is an isomer of vitamin E.<br />

Sunscreens — Include avobenzone,<br />

octocrylene, titanium dioxide or zinc oxide.<br />

10 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

Based on in vitro experiments, vitamin C has been shown to promote collagen synthesis.<br />

Cosmetic studies demonstrate several skin anti-aging effects from the use of<br />

topical vitamin C. 3% ascorbic acid has been shown to reduce oxidative damage by<br />

neutralizing free radicals as well as to reduce facial wrinkles. 5–17% ascorbic acid<br />

minimizes facial photoaging, improves skin texture and increases skin elastin.<br />

Neutralizes harmful free radicals and protects skin from damaging effects. Higher levels<br />

of CoQ10 result in increased production of collagen and elastin. Penetrates epidermal<br />

layers to reduce level of oxidation and diminish depth of fi ne lines/wrinkles.<br />

Experiments treating cells in culture with N-acetyl-glucosamine have demonstrated signifi<br />

cant increases in both hyaluronic acid and collagen. In human clinical testing, topically<br />

applied NAG improves skin moisturization as well as the appearance of fi ne lines/wrinkles.<br />

In vitro experiments establish that niacinamide increases collagen production,<br />

decreases sebum production and increases barrier-containing lipids and proteins.<br />

Clinical studies have demonstrated a range of benefi ts including a reduction<br />

in the appearance of fi ne lines and wrinkles, minimized skin pore size and<br />

decreased appearance of hyper-pigmented spots, blotchiness and skin sallowness.<br />

In vitro studies of cells treated with panthenol demonstrate increased synthesis of stratum<br />

corneum lipids. Topically-applied panthenol in human clinical testing has shown increased<br />

hydration of the stratum corneum and improved roughness and elasticity of skin.<br />

In vitro studies prove that synthetic pal-KTTKS stimulates collagen production and<br />

reduces excess dermal GAGs. In addition, in vitro pal-KT enhances the reduction of<br />

collagen alone and synergistically with pal-KTTKS. Clinical studies show topical pal-<br />

KTTKS and pal-KT products improve the appearance of wrinkles and texture.<br />

In vitro studies demonstrate retinoid-induced changes in the expression of genes<br />

relevant to dermal matrix production, epidermal differentiation and melanin production.<br />

Specifi cally, retinoids stimulate the production of collagen and decrease<br />

the production of dermal GAGs. Retinoids have also been shown to increase the<br />

production of epidermal hyaluronic acid. Clinical studies demonstrate that topical<br />

doses of retinoids less than 1% are signifi cantly effective in reducing hyperpigmentation,<br />

roughness and the appearance of facial fi ne lines/wrinkles.<br />

Salicylic Acid proves to exfoliate the stratum corneum resulting in improved skin<br />

texture and color appearance. Clinical studies of topical salicylic acid have demonstrated<br />

improvements in the appearance of wrinkling, roughness and discoloration.<br />

In in vitro experiments, antioxidants neutralize free radicals, protect skin<br />

cells from oxidation and thwart other antioxidants from oxidizing. In particular,<br />

tocopherol has the potential to improve skin problems caused by UV exposure<br />

such as sunburn, skin photoaging and hyperpigmentation. Used topically,<br />

these antioxidants have been shown to diminish the appearance of aging.<br />

Chemical sunscreens absorb UV radiation while physical sunscreens block UV rays.<br />

A physical or “broad spectrum” sunscreen is an effi cient tool to protect against<br />

both UVA and UVB rays, which contribute to wrinkles, freckles and age spots.<br />

Prevents<br />

Repairs<br />

Prevents<br />

& Repairs


What Works<br />

In recent years, science has uncovered<br />

a great deal about how to prevent<br />

extrinsic skin aging as well as<br />

the anti-aging benefi ts of retinoids,<br />

niacinamide and peptides.<br />

Prevention of Extrinsic Skin Aging<br />

Everyone has heard the old adage<br />

that an ounce of prevention equals<br />

a pound of cure, but in the arena of<br />

skin science, it is only recently that<br />

we’ve gained a clearer understanding<br />

of what should be prevented and how.<br />

Th anks to research advancements,<br />

we now know both the consequences<br />

of extrinsic factors and what can be<br />

done to avoid, or at least limit, their<br />

deleterious eff ects.<br />

In the area of UV protection,<br />

increased understanding of the role<br />

of UVA rays in both cancer and skin<br />

aging has led to stronger emphasis on<br />

“broad spectrum” coverage that protects<br />

against UVA and UVB rays, as<br />

well as the introduction of improved<br />

UVA fi lters. Th is progress is continuing<br />

to be built upon through<br />

enhanced technologies that deliver<br />

the protection consumers need along<br />

with the product aesthetics we know<br />

improve sunscreen compliance. 33<br />

Progress has also been made in better<br />

understanding the role of antioxidants<br />

in inhibiting reactive oxygen<br />

species (ROS) formation and thereby<br />

interrupting free radical chain propa-<br />

gation, a major pathway for UV- and<br />

other environmentally-induced skin<br />

damage. In a recent study, P&G<br />

<strong>Beauty</strong> researchers 34 used fl uorescence<br />

microscopy to visualize and<br />

quantify the protective eff ect of topically-applied<br />

antioxidants for inhibiting<br />

ROS formation across several<br />

sources of oxidative stressors, including<br />

UV light, automotive emissions<br />

and ozone. Th e effi cacy of sunscreen<br />

alone and in combination with antioxidants<br />

was also evaluated.<br />

Key fi ndings include:<br />

• Topically applied antioxidant<br />

formulations were eff ective at<br />

signifi cantly inhibiting free radical<br />

formation, with reductions of<br />

19–88% versus antioxidant-free<br />

vehicle controls observed against<br />

three oxidative stressors.<br />

• An antioxidant/SPF 15 formulation<br />

gave signifi cantly reduced ROS<br />

(91% reduction) versus either<br />

antioxidant-only (88% reduction)<br />

or SPF-only (61% reduction) controls<br />

(p


Retinoids include:<br />

• Retinol<br />

• Retinaldehyde<br />

• Retinyl Esters (retinyl propionate,<br />

retinyl palmitate)<br />

• Tretinoin (trans-retinoic acid)<br />

• Adapalene<br />

• Tazarotene<br />

moderate skin irritation that may<br />

persist over the course of topical<br />

use, 36 and the associated teratogenic<br />

eff ects. In recent years, new synthetic<br />

derivatives of vitamin A that have<br />

been developed for use on human<br />

skin minimize cutaneous irritation<br />

and other unwanted eff ects. Clinical<br />

trials comparing retinol to retinyl<br />

esters suggest that retinyl propionate,<br />

the propionic acid ester of retinol,<br />

delivers skin benefi ts that are similar<br />

to using retinol (e.g., improvement<br />

in appearance of wrinkles and<br />

pigment spots) but with less irritation.<br />

37 Because of the skin’s enhanced<br />

sensitivity to sunlight when using<br />

retinoids, adequate sun protection<br />

must be factored into treatment. A<br />

12-week study evaluated the use of<br />

retinol and retinyl propionate both<br />

co-applied with sunscreen. Th ose<br />

using retinyl propionate and sunscreen<br />

showed a signifi cant reduction<br />

in the appearance of wrinkles and<br />

sunspots with no irritation. Con-<br />

12 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

Baseline After 12 Weeks<br />

Effect of retinyl propionate upon photodamaged skin. 0.2% retinyl propionate in a<br />

stable skin care emulsion system was applied twice daily for 12 weeks. Images were<br />

taken at baseline and week 12.<br />

versely, the retinol-sunscreen combination<br />

appeared to exacerbate skin<br />

irritation and lessened the skin benefi<br />

ts. 37 Retinyl propionate appears to<br />

off er dermatologists a milder, more<br />

tolerable form of retinoid that can<br />

improve the look of photoaged skin,<br />

while guarding against additional sun<br />

damage and irritation.<br />

Niacinamide<br />

Topical niacinamide, a water-soluble<br />

derivative of vitamin B3, provides<br />

a host of dermatological therapeutic<br />

benefi ts. Clinical research provides<br />

grow ing evidence for its positive<br />

eff ects on skin health, from help-<br />

ing maintain barrier integrity<br />

29, 30,<br />

38, 39, 40 to diminishing the signs<br />

of aging, including: (1) reducing fi ne<br />

lines and wrinkles, 29 (2) reducing<br />

texture problems by diminishing<br />

the appearance of pores 41, 42 and (3)<br />

improving skin tone by reducing the<br />

appearance of hyperpigmentation,<br />

skin yellowing and red blotchiness. 29<br />

Niacinamide is also well-tolerated<br />

and compatible with other anti-aging<br />

technologies, making it an ideal<br />

choice for skin care. 29 In fact, it has<br />

recently been shown that the use of<br />

niacinamide-containing moisturizer<br />

during topical tretinoin therapy mitigates<br />

the severity of side eff ects and<br />

augments the treatment response. 43<br />

Th e eff ects of niacinamide on skin<br />

cells in culture have been explored<br />

extensively. Niacinamide has been<br />

shown to be a key player in the normalization<br />

of age-associated depletions<br />

of nicotinamide coenzymes.<br />

Th is is of particular importance for<br />

aged skin since systemic and intracellular<br />

concentrations of the nicotinamide<br />

coenzymes NADH and<br />

NADPH decline with age in human<br />

and animal models. 44, 45, 46 Th ese<br />

cofactors are critical drivers of both<br />

catabolic and anabolic processes<br />

within cells including the production<br />

and maintenance of the dermis. In


Effect Of Niacinamide On Increase In Collagen Synthesis In Human Dermal Fibroblasts<br />

particular, niacinamide supplementation<br />

has been shown to stimulate<br />

collagen synthesis in human dermal<br />

fi broblasts, 47 an eff ect that would be<br />

of particular signifi cance in aged and<br />

photodamaged skin.<br />

Multiple clinical studies have demonstrated<br />

the positive eff ects of niacinamide-containing<br />

moisturizers on the<br />

appearance of wrinkles and fi ne lines<br />

in aging skin. 29, 48 In one, 29 a 12-week<br />

randomized, split-face trial, 50 female<br />

subjects applied blind-coded product<br />

Total protein Total collagen<br />

Collagen: total<br />

protein ratio<br />

500uM niacinamide 41% 54% 35%<br />

These data demonstrate that niacinamide treatment has a positive effect on collagen production relative to<br />

control and that there is specifi city for collagen biosynthesis and secretion relative to other cellular proteins.<br />

BETTER<br />

Change in fine lines/wrinkles area vs. baseline<br />

5.00 –<br />

0.00 –<br />

-5.00 –<br />

-10.00 –<br />

-15.00 –<br />

-20.00<br />

followed by image analysis. Signifi cant<br />

improvements were seen in several<br />

facial parameters including appearance<br />

of fi ne lines and wrinkles (p=0.06 at<br />

week 8 and 0.0005 at week 12).<br />

In another study, 40 female subjects<br />

applied blind-coded products in a<br />

split-face design for 12 weeks. Significant<br />

improvements in skin texture<br />

including fi ne line appearance were<br />

observed in niacinamide-treated skin<br />

at both four and 12 weeks of treatment<br />

(p


Peptides<br />

Th e use of peptides in commercial<br />

products has signifi cantly risen in<br />

recent years. Known to play a role in<br />

wound-healing, naturally occurring<br />

peptides in the skin have been shown in<br />

vitro to: (1) stimulate the production<br />

of extracellular matrix components<br />

including collagen, elastin and fi bronectin<br />

and (2) decrease the production<br />

of dermal GAGs. 49, 50 Decreased<br />

dermal matrix components and<br />

increased dermal GAGs are hallmark<br />

features of aged skin, 51 the reversal of<br />

which has been hypothesized as a viable<br />

approach to anti-aging.<br />

With variations in amino acid<br />

sequence, number of amino acids<br />

and use of derivatives of these acids,<br />

there are limitless combinations of<br />

possible peptides. By testing the eff ect<br />

of multiple peptides on the synthesis<br />

of collagen in culture, scientists<br />

at the University of Tennessee<br />

49, 50<br />

narrowed the fi eld of possible amino<br />

acid combinations to a pentapeptide<br />

fragment of pro-collagen, KTTKS<br />

(lysine-threonine-threonine-lysineserine).<br />

Th is peptide retained 80%<br />

of the collagen-stimulating activity<br />

of the original, much larger 34–44<br />

amino acid pro-collagen peptide<br />

from which it was derived.<br />

Because transdermal delivery of ionic<br />

peptides is likely to pose a signifi cant<br />

issue for delivery of bioactive peptide<br />

into the skin, a palmitoyl derivative<br />

14 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

Collagen synthesis (% of control)<br />

250 –<br />

200 –<br />

150 –<br />

100 –<br />

50 –<br />

0<br />

Control 4ppm pal-KTTKS<br />

In cell culture experiments, pal-KTTKS increases<br />

collagen synthesis.<br />

–<br />

–<br />

of KTTKS (pal-KTTKS) was used,<br />

which capitalizes on research conducted<br />

on peptides to improve transcutaneous<br />

delivery. 52<br />

Consistent with the collagenstimulating<br />

eff ects of the underivatized<br />

KTTKS, pal-KTTKS promotes<br />

the production of collagen in organotypic<br />

cultures of human skin cells. 24<br />

In addition, pal-KTTKS eff ectively<br />

reduces dermal GAGs at 1/10 th the<br />

dose of trans-retinoic acid (tRA). 53<br />

Th e promotion of these eff ects in<br />

vitro are consistent with the antiaging<br />

strategy proposed above.<br />

Multiple clinical studies have demonstrated<br />

the signifi cant eff ect of formu<br />

lations containing pal-KTTKS on<br />

wrinkle reduction and facial appearance<br />

improvement. In one study, 54<br />

60 subjects were treated for four<br />

months in a split-faced doubleblinded<br />

trial. Th e pal-KTTKS<br />

test product produced signifi cant<br />

% reduction in GAGs<br />

% change over 4 months<br />

70 –<br />

60 –<br />

50 –<br />

40 –<br />

30 –<br />

20 –<br />

10 –<br />

0<br />

5 –<br />

0 –<br />

-5 –<br />

-10 –<br />

-15 –<br />

-20 –<br />

-25 –<br />

-30 –<br />

-35 –<br />

-40<br />

0.9ppm<br />

pal-KTTKS<br />

% change vs. To p< 0.01 % change vs. To p< 0.015<br />

Wrinkle volume<br />

(μm 3 )<br />

–<br />

5 –<br />

0 –<br />

-5 –<br />

-10 –<br />

-15 –<br />

-20 –<br />

-25 –<br />

-30<br />

¢ pal-KTTKS<br />

¢ tRA control<br />

10ppm tRA<br />

(*10ppm = 0.001%)<br />

In in vitro cell culture experiments, pal-KTTKS<br />

reduces GAGs comparably at 1/10 th the dose of<br />

tRA (10 ppm = 0.001%).<br />

¢ pal-KTTKS<br />

¢ Vehicle<br />

Wrinkle depth<br />

(μm)<br />

Moisturizer containing pal-KTTKS decreases both<br />

wrinkle volume and depth following 4 months of<br />

treatment.<br />

–<br />

improve ments versus the vehicle in<br />

wrinkle volume and wrinkle depth<br />

at two- and four-month time points.<br />

Results were based on quantitative<br />

image analysis of skin replicas.<br />

In another split-face double-blinded<br />

study of 92 subjects, 27 signifi cant


improvements were seen in wrinkle<br />

appearance (week 12 p=


16 <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> and <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

Infl ammatory<br />

Responses &<br />

Their Relationship<br />

to Skin<br />

Infl ammatory responses, which occur<br />

in the vascularized connective tissue,<br />

are intended to be protective, destroying<br />

the organism of both the initial<br />

cause of cell injury (e.g., microbes,<br />

toxins) and the consequences of<br />

such injury (e.g., necrotic cells and<br />

tissues). Without infl ammation,<br />

infections would go unchecked and<br />

wounds would not heal; however, the<br />

process of infl ammation and repair<br />

can also be harmful. Infl ammatory<br />

mechanisms play a key role in the<br />

pathogenesis of chronic conditions<br />

including cardiovascular disease,<br />

colorectal cancer, stroke, type 2 diabetes,<br />

COPD and Alzheimer’s disease.<br />

It is also increasingly recognized<br />

as a potent independent predictor<br />

of all-cause mortality. Th e risk of<br />

chronic infl ammation correlates with<br />

increasing age and certain lifestyle<br />

factors, including smoking, obesity<br />

and poor dietary patterns.<br />

Th e term “infl ammaging” was coined<br />

by Claudio Franceschi 58 to describe<br />

the cascade of autoimmune infl ammatory<br />

responses that lead to chronic<br />

low-level infl ammation. Infl ammaging<br />

is a useful clinical construct<br />

because we know that all the major<br />

diseases associated with aging share<br />

an infl ammatory pathogenesis. Th e<br />

defi ning characteristic of infl ammaging<br />

is an up-regulation of multiple<br />

anti-stress responses at the cellular<br />

and molecular level. Th is rampant<br />

up-regulation of anti-stress responses<br />

in turn leads to the accumulation of<br />

molecular and cellular scars.<br />

Th e biological processes that characterize<br />

infl ammaging are also applicable<br />

to skin, as we are gaining an<br />

increased awareness of the importance<br />

of chronic infl ammation in the<br />

promotion of skin aging. Activated<br />

infl ammatory cells resulting from elevations<br />

in circulating pro-infl ammatory<br />

hormones (e.g., prostaglandins,<br />

cytokines, histamines) eff ectively<br />

produce ROS that cause oxidative<br />

damage to nucleic acids, cellular proteins<br />

and lipids. Accumulated ROS<br />

stimulates a host of cytokine cascades<br />

that result in photoaging and<br />

photocarcinogenesis. Th ese changes<br />

are directly tied to the appearance of<br />

aging skin. 5<br />

Putting the Pieces Together:<br />

Genomics, Infl ammation<br />

& Skin Aging<br />

Utilizing the sophisticated tools of<br />

genomics, P&G <strong>Beauty</strong> researchers<br />

are learning more about infl ammatory<br />

pathways and their eff ects on<br />

skin aging. One of these research<br />

endeavors was presented by Michael<br />

Robinson, PhD, at the 21 st World<br />

Congress of Dermatology. 59 Th e


study compared the sun-exposed skin<br />

of the forearm and the sun-unexposed<br />

skin of the buttocks in both<br />

young and older clinical test subjects.<br />

Gene chip technology allowed the<br />

researchers to identify exact processes<br />

and metabolic pathways that were<br />

diff erent in young versus old skin.<br />

Additionally, it allowed scientists to<br />

identify pathways that were active in<br />

young skin but were inactive in old<br />

skin as well as pathways that were<br />

overly active in the older skin, such<br />

as infl ammation.<br />

Genes observed in the older clinical<br />

test subjects shared consistent<br />

themes, including:<br />

• Immune and infl ammatory re -<br />

sponse genes were up-regulated<br />

• Extra-cellular matrix genes were<br />

up-regulated, though photoaging<br />

was more commonly associated<br />

with collagen gene changes and<br />

Summary<br />

<strong>Wrinkles</strong>, fi ne lines and uneven skin texture are<br />

persistent and universal concerns of aging patients, particularly<br />

women. But new innovations in topical treatments<br />

are allowing these concerns to be addressed both<br />

through preventative care, specifi cally the inclusion of<br />

ingredients that protect against UV-related damage,<br />

and restorative skin creams that deliver anti-aging<br />

benefi ts. Ingredients that have been shown to unequivocally<br />

deliver wrinkle, fi ne line and texture benefi ts<br />

include niacinamide, peptides, retinyl propionate and<br />

N-acetyl glucosamine.<br />

chronological skin aging with keratin<br />

gene changes<br />

• Protease/peptidase activity was upregulated<br />

• Oxidoreductase activity and epidermal<br />

development process genes<br />

were down-regulated<br />

Th e overarching theme, of course, is<br />

that an infl ammatory response was<br />

observed in older and photodamaged<br />

skin. By understanding how<br />

specifi c genes are modulated by the<br />

aging process, scientists now have the<br />

means to tailor treatments to shut<br />

down those processes which age the<br />

skin considerably.<br />

Th is study is just the beginning of<br />

the potential that is possible through<br />

gene chip technology. Th rough an<br />

analysis of these pathways at the gene<br />

expression level, these researchers<br />

are making discoveries that will ultimately<br />

lead to advances in cosmetic<br />

options for consumers. Spurred<br />

by the promising fi ndings to date,<br />

P&G <strong>Beauty</strong> scientists are continuing<br />

to explore this new frontier across<br />

multiple research end points. For<br />

the growing ranks of patients who<br />

seek non-invasive solutions to common<br />

dermatological problems, gene<br />

chip technology provides an understanding<br />

of skin aging never before<br />

possible, and, in doing so, off ers<br />

extraordinary potential for improving<br />

topical anti-aging treatments.<br />

This fi gure is illustrative of the combined effects<br />

of aging and photodamage at the gene expression<br />

level. The blue color indicates genes that<br />

are down-regulated; red, up-regulated; and white<br />

indicates no change. It is clear that there are large<br />

clusters of genes that are differentially regulated<br />

in young versus older photodamaged skin.<br />

Th rough refi ned applications of complex sciences and<br />

advanced technologies, P&G <strong>Beauty</strong> researchers are<br />

gaining a more complete picture of the underlying biological<br />

processes at work in aging skin. Th is methodological<br />

process has led to the ability to identify gene<br />

targets and tailor topical interventions accordingly. One<br />

dominant theme that has emerged is the age-related<br />

process of infl ammation, and thought leaders predict<br />

future anti-aging research and treatments will further<br />

expand upon and apply this body of knowledge.<br />

<strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> and <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong> 17


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57. P&G <strong>Beauty</strong> data on fi le<br />

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Aires, Argentina; 2007.


AN ADDITIONAL TOOL<br />

The <strong>Fine</strong> <strong>Lines</strong>, <strong>Wrinkles</strong> & <strong>Texture</strong>: <strong>Research</strong> <strong>Update</strong><br />

CD holds a PowerPoint presentation of the charts and<br />

illustrations in this toolkit. Feel free to use the images.<br />

Please credit P&G <strong>Beauty</strong>.


CONTACT INFORMATION<br />

To talk with a P&G scientist or<br />

to learn more about ongoing<br />

research in the <strong>Beauty</strong> Science<br />

division, visit pgbeautyscience.com,<br />

or contact:<br />

Dianna Kenneally<br />

P&G <strong>Beauty</strong> Science<br />

513-626-3508<br />

Heather Cunningham<br />

P&G <strong>Beauty</strong> Science<br />

513-626-2606

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