REGU -SCENCE - seralabshealth.com · containing 3% REGU®-SCENCE and a placebo, one to each side of...

REGU®-SCENCEDelaystheappearanceofskinagingbydecades

Autophagy is the key process by which cellular waste is removed or recycled. The process starts with the formation of double membrane structures (phagophores). The phagophores then close and form autophagosomes, which sequester damaged cell components. Each autophagosome fuses with a lysosome to form an autolysosome, in which waste matter is degraded by lysosomal enzymes into amino acids, fatty acids, sugars, and nucleotides.

These newly formed molecules are now liberated from the autolysosome and can be used for the neo-synthesis of functional biomolecules and for the generation of ATP (improved energy supply).

Autophagy: an essential biochemical housekeeping process

Key factsUnique product features •Helpsstimulatetheskin’sownautophagycapabilities,slowingtheprocessofcellularsenescence*

• In vivosignificantlyimprovescollagendensityanddermisthickness

•Ex vivoalmostcompletelyprotecteddonorskinagainstsignsofsunburncausedbyexposuretoUVradiation

•MadespecificallyfromNavarraAsparagus officinalis‘Grolim’,whichhasaparticularlyhighactivemoleculecontent

Benefits•Boostsskin’sinnatestrengthtodelaycellularagingbydecades

•Stimulatesskin’sdetoxifyingprocesses,independentlyofage

•Providesanoverallskinrejuvenationeffect

Cosmetic application•Skinagingpreventionfor25+•Rejuvenatingintensecarefor40+•Multifunctionalbeautycareproducts,suchasBBorCC

Suggested concentration•1–3%ofaNavarraAsparagus officinalis‘Grolim’extractbasedingredientincosmeticformulations

INCI name (Active)Asparagus officinalisStemExtract

Aging skin tends to lose its look of youthful resilience and elasticity. Skin aging is the number one cosmetic concern. Scientific data show that skin layers thin and the concentration of proteins such as collagen decreases.

In response, DSM has developed a carefully purified, standardized plant bioactive made exclusively from Navarra Asparagus officinalis ‘Grolim’. Its unique mechanism of action helps reduce visible signs of the naturally occurring cellular aging process known as senescence, delaying the appearance of skin aging by decades.

Extended studies have confirmed that Navarra Asparagus officinalis ‘Grolim’ extract significantly combats two major signs of skin aging by giving the skin a firmer, thicker appearance. Consequently, Navarra Asparagus officinalis ‘Grolim’ extract can leave skin looking rejuvenated.

Your inner beautician

The Asparagus officinalis ‘Grolim’ for DSM’s age-defying new ingredient is exclusively cultivated in Navarra, northern Spain. Conditions here are optimal for asparagus growing, with incredibly fertile soil composed of clayish loam, having a slightly elevated pH and a high organic content. Navarra also has the ideal spring climate for asparagus growing, with cold nights below 12°C and warmer days.

Asparagus cultivation is particularly labor intensive. In Navarra harvesting is carried out manually before sunrise to preserve the quality of the product and ensure it can be delivered fresh the same day. And around 340 physicochemical analyses are routinely performed each season, ensuring that Navarra asparagus remains among the most exquisite available and superior to almost any other variety in the world.

Navarra delivers exceptional high-quality Asparagus

REGU®-SCENCE Raw material approved by ECOCERT GREENLIFE, conform to the ECOCERT Natural and Organic Cosmetics Standard

* in vitro immunofluorescent detection of LC3 protein (key autophagic marker) in fibroblasts in monolayer culture.

MechanismIn the course of their work, for example producing energy or functional molecules, cells naturally generate waste matter. Moreover, external influences such as UV irradiation or reactive oxygen species (ROS) increase cellular stress which in turn leads to the release of malfunctioning organelles and protein waste within the cells. Fortunately, cells have their own detoxifying and recycling system, a process known as autophagy. Autophagy is the ability of the cells to collect malfunctioning substances and recycle them as functional amino acids, fatty acids, sugars, and nucleotides. These recycled substances are then available for the neo-synthesis of functional biomolecules and for metabolic energy supply.

Autophagy is a very efficient process that not only cleans cells of waste but also regenerates cellular functionality.

However, as cells mature progressively they ultimately stop dividing and enter a state called senescence, which is characterized by reduced metabolic functionality. As part of this aging process, autophagic activity decreases and therefore the cells are no longer able to fully process their waste. Reducing the tell-tale signs of skin cell senescence could represent a key step towards unlocking exciting new possibilities for products that delay the appearance of skin aging.

STRESSCELLULAR

Young skin

AUTOPHAGY

REDUCEDAUTOPHAGY

INCREASEDINCREASED

Recyclin

g of c

ellu

lar w

aste

and protein junk into amino acids, fatty acids, sugars, nucleotides

Aging skin

SENE

SCEN

CE

NEO-SYNTHESIS OFFUNCTIONAL BIOMOLECULES

ENERGY SUPPLY


ENERGY SUPPLY


ENERGY SUPPLY

STRESSCELLULAR

It is known that, as skin ages, the rate of autophagy is reduced and an imbalance arises between the rates of protein synthesis and degradation. This leads to an accumulation of damaged proteins which in turn increases oxidative stress within the cells, causing more protein and DNA damage and giving rise to a negative feedback loop with increased cellular senescence. Extended tests have demonstrated the ability of Navarra Asparagus officinalis ‘Grolim’ extract to reduce the visible effects of these processes and delay the signs of skin senescence.

• In vitro assays demonstrated that Navarra Asparagus officinalis ‘Grolim’ extract increased the rate of autophagy in fibroblasts from older donors until levels were similar to those seen in cells from young donors. The number of cells becoming senescent decreased.*

• Inex-vivo assays in which donor skin was exposed to UV radiation simulating sunburn conditions, Navarra Asparagus officinalis ‘Grolim’ extract almost completely protected the skin against visible signs of damage.

• InaconsumerstudywewereabletoshowthatNavarraAsparagus officinalis ‘Grolim’ extract significantly improved the appearance of two major signs of skin aging.

Generic autophagy processes

* in vitro immunofluorescent detection of LC3 protein (key autophagic marker) in fibroblasts in monolayer culture.

Efficacy in vitro*

Stimulation of autophagic activity

LC3 protein is the key marker for autophagy as it is involved in autophagosome formation and function, and is present during the whole autophagy process.

The presence of LC3 in autophagosomes has been determined by microscopic immunofluorescence imaging technology.

Result:Navarra Asparagus extract significantly and dose-dependently stimulates autophagy key marker LC3, as shown by the up to 49% increase in fluorescence intensity.

Untreated Treated with 100 ppmNavarra Asparagus Extract

The stimulated LC3 proteins are stained with green fluorescence

Day 0

0.95mm 1.12mm

Day 56

+18%*

-62%*

*/**10

9

8

7

6

5

4

3

2

1

0

Colla

gen

dens

ity va

riatio

n co

mpa

red

to D

ay 0

(%)

Day 56

in vivo Collagen density

* Sig

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5. D

evice

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e

+8%**

+44%*

1.15

1.1

1.05

1.0

0.95

0.9

0.85

Derm

is th

ickn

ess

(mm

)

3% REGU®-SCENCEPlacebo


Day 56

in vivo Dermis thickness

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3% NavarraAparagus o�cinalis

extract ‘Grolim’ basedingredient

Irradiated Irradiated and 3%Navarra Aparaguso�cinalis extract

‘Grolim’ based ingredient

70

60

50

40

30

20

10

0

% s

tain

ed s

urfa

ce o

f oxi

dize

d pr

otei

ns

Oxidized proteins

Untreated

150

140

130

120

110

100

90

80

70

60

50

40

30

20

0

Fluo

resc

ence

inte

nsity

(%)

Autophagy assay

* Sig

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100 ppmNavarra

Asparagusextract

200 ppmNavarra

Asparagusextract

Untreatedcontrol

Day 0

0.95mm

Day 56

1.04mm

1491291007.51.5

+49%*

+29%*

3.0

2.8

2.6

2.4

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

Colla

gen-

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is (f

old)

Collagen Assay

* Sig

ni�c

ant l

evel

= p

<0.0

03

Chinese Asparagus Stem(dry extract)

Untreatedcontrol

0.002%

1.911.00

0.004%

1.91

REGU®-SCENCE(dry extract)

0.001%

2.26

0.002%

2.75

Stimulation of autophagic activity in human dermal fibroblasts from aged donorAutophagic activity is strongly reduced in cells from aging skin.

The previous assay was repeated on skin cells from young and from older donors.

Result:100 ppm Navarra Asparagus extract drastically increases the rate of autophagy in fibroblasts from older donors until levels are similar to those seen in cells from young donors.

Cellular senescenceSenescence, or biological aging, is a natural process that contributes to skin aging. Senescent cells have a reduced metabolism, they stop dividing, and remain in a passive state. This leads to a changed phenotype including flattened cell morphology, altered gene expression, and positive senescence-associated β-galactosidase staining.

In this assay, bluish staining shows β -galactosidase activity of senescent cells.

Result:100 ppm Navarra Asparagus officinalis ‘Grolim’ extract delays visible signs of skin senescence.

Untreated

Treated with Navarra Asparagus officinalis ‘Grolim’ extract

Untreated

Treated with Navarra Asparagus officinalis ‘Grolim’ extract

28 years old 62 years old




* in vitro tests in monolayer culture.

Result:After 56 days, 3% REGU®-SCENCE: • significantlyincreasestheappearanceofdermisthicknessby

18% compared to Day 0.• significantlyincreasestheappearanceofdermisthickness

compared to placebo.

31 female volunteers (40–55 years old) applied an emulsion containing 3% REGU®-SCENCE and a placebo, one to each side of their face, twice a day for 56 days.

The variation in collagen density was quantified by means of a SIAscope. The SIAscope emits a controlled light from a probe placed on the skin. The light reflection is characterized by the layered nature of skin tissue encountered.

in vivo

Protein oxidation

One harmful consequence of increased cellular stress is the oxidative modification of proteins. As a result of this modification, carbonyl groups are introduced into protein side chains. These carbonyl groups are a hallmark of the oxidation status of proteins. Protein oxidation after UV-irradiation was detected in human skin explants by an immunological detection method.

Skin explants from a 50-year-old donor were treated with a medium or with 3% of a Navarra Asparagus officinalis ‘Grolim’ extract based ingredient. After 5 days, the cells were irradiated with UVA (18 J/cm2) and UVB (0.6 J/cm2).

Protein oxidation was analyzed 1 day and 4 days after irradiation.

Result:Navarra Asparagus officinalis ‘Grolim’ extract almost completely protected the appearance of skin which had undergone exposure to UV radiation simulating sunburn conditions.

Day 0

0.95mm 1.12mm

Day 56

+18%*

-62%*

*/**10

9

8

7

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3

2

1

0

Colla

gen

dens

ity va

riatio

n co

mpa

red

to D

ay 0

(%)

Day 56


* Sig

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ant l

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evice

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+8%**

+44%*

1.15

1.1

1.05

1.0

0.95

0.9

0.85

Derm

is th

ickn

ess

(mm

)



Day 56


* Sig

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70

60

50

40

30

20

10

0

% s

tain

ed s

urfa

ce o

f oxi

dize

d pr

otei

ns

Oxidized proteins

Untreated

150

140

130

120

110

100

90

80

70

60

50

40

30

20

0

Fluo

resc

ence

inte

nsity

(%)

Autophagy assay

* Sig

ni�c

ant l

evel

= p

<0.0

5. A

utop

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c act

ivity

mea

sure

d by

flow

cyto

met

ry

100 ppmNavarra

Asparagusextract

200 ppmNavarra

Asparagusextract

Untreatedcontrol

Day 0

0.95mm

Day 56

1.04mm

1491291007.51.5

+49%*

+29%*

3.0

2.8

2.6

2.4

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

Colla

gen-

I syn

thes

is (f

old)

Collagen Assay

* Sig

ni�c

ant l

evel

= p

<0.0

03


Untreatedcontrol

0.002%

1.911.00

0.004%

1.91


0.001%

2.26

0.002%

2.75

Result:After 56 days, 3% REGU®-SCENCE: • significantlyincreasescollagendensityby7.5%comparedtoDay0.• significantlyincreasescollagendensitycomparedtoplacebo.

Day 0

0.95mm 1.12mm

Day 56

+18%*

-62%*

*/**10

9

8

7

6

5

4

3

2

1

0

Colla

gen

dens

ity va

riatio

n co

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red

to D

ay 0

(%)

Day 56


* Sig

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+8%**

+44%*

1.15

1.1

1.05

1.0

0.95

0.9

0.85

Derm

is th

ickn

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(mm

)



Day 56


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ions





70

60

50

40

30

20

10

0%

sta

ined

sur

face

of o

xidi

zed

prot

eins

Oxidized proteins

Untreated

150

140

130

120

110

100

90

80

70

60

50

40

30

20

0

Fluo

resc

ence

inte

nsity

(%)

Autophagy assay

* Sig

ni�c

ant l

evel

= p

<0.0

5. A

utop

hagi

c act

ivity

mea

sure

d by

flow

cyto

met

ry

100 ppmNavarra

Asparagusextract

200 ppmNavarra

Asparagusextract

Untreatedcontrol

Day 0

0.95mm

Day 56

1.04mm

1491291007.51.5

+49%*

+29%*

3.0

2.8

2.6

2.4

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

Colla

gen-

I syn

thes

is (f

old)

Collagen Assay

* Sig

ni�c

ant l

evel

= p

<0.0

03


Untreatedcontrol

0.002%

1.911.00

0.004%

1.91


0.001%

2.26

0.002%

2.75

ex vivo

Oxidized proteins are stained in dark purple. These pictures show that despite irradiation, the skin treated with the Navarra Asparagus officinalis ‘Grolim’ extract based ingredient exhibits a similar level of oxidized proteins to the non-irradiated skin.

Day 0

0.95mm 1.12mm

Day 56

+18%*

-62%*

*/**10

9

8

7

6

5

4

3

2

1

0

Colla

gen

dens

ity va

riatio

n co

mpa

red

to D

ay 0

(%)

Day 56


* Sig

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= p

<0.0

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red

to p

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<0.0

5. D

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: Sia

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+8%**

+44%*

1.15

1.1

1.05

1.0

0.95

0.9

0.85

Derm

is th

ickn

ess

(mm

)



Day 56


* Sig

ni�c

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70

60

50

40

30

20

10

0

% s

tain

ed s

urfa

ce o

f oxi

dize

d pr

otei

ns

Oxidized proteins

Untreated

150

140

130

120

110

100

90

80

70

60

50

40

30

20

0

Fluo

resc

ence

inte

nsity

(%)

Autophagy assay* S

igni

�can

t lev

el =

p<0

.05.

Aut

opha

gic a

ctivi

ty m

easu

red

by fl

ow cy

tom

etry

100 ppmNavarra

Asparagusextract

200 ppmNavarra

Asparagusextract

Untreatedcontrol

Day 0

0.95mm

Day 56

1.04mm

1491291007.51.5

+49%*

+29%*

3.0

2.8

2.6

2.4

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0

Colla

gen-

I syn

thes

is (f

old)

Collagen Assay

* Sig

ni�c

ant l

evel

= p

<0.0

03


Untreatedcontrol

0.002%

1.911.00

0.004%

1.91


0.001%

2.26

0.002%

2.75

Non-irradiated skin,untreated

UV irradiated skin,untreated,4 days after irradiation

UV irradiated skintreated with 3% of the tested ingredient4 days after irradiation

©2014DSMNutritionalProductsAG,4002Basel,Switzerland.www.dsm.com/personal-careAllrightsreserved.Nopartofthisbrochuremaybereproduced,distributedortranslatedinanyformorbyanymeans,orstoredinadatabaseorretrievalsystem,withoutthepriorwrittenpermissionofDSMNutritionalProductsAG(“DSM”).Whilemakingreasonableeffortstoensurethatallinformationinthisbrochureisaccurateanduptodate,DSMmakesnorepresentationorwarrantyoftheaccuracy,reliability,orcompletenessoftheinformation.Useofthisinformationshallbeatyourdiscretionandrisk.Nothinghereinrelievesyoufromcarryingoutyourownsuitabilitydeterminationsandtestsandfromyourobligationtocomplywithallapplicablelawsandregulationsandtoobserveallthirdpartyrights.TheusesandclaimsforDSM’sproductsrecommendedinthebrochureshouldbeadaptedtothecurrentlocalregulatoryenvironment.Wedisclaimanyandallliabilityinconnectionwithyourproductoritsuse.

P0064

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REGU -SCENCE - seralabshealth.com · containing 3% REGU®-SCENCE and a placebo, one to each side of...

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