18 replies to this topic

[stephen_b]

I hope that this isn't perceived as too naive a question, but what factors account for the appearance of aged skin? Perhaps the answer to that is the same is the answer to aging in general.

I saw this study, PMID 16374460:
The Receptor for Advanced Glycation End Products Is Highly Expressed in the Skin and Upregulated by Advanced Glycation End Products and Tumor Necrosis Factor-Alpha (with a title like that, who needs to post an abstract ).

Is it a stretch to say that AGE accumulation in the skin is the primary cause of the characteristic appearance of skin of those in their eighties and older, or do DNA damage by UV light or shortening telomeres play the greater role?

Stephen

[lunarsolarpower]

More interesting to me would be to skip asking what is wrong and instead ask what can be done to rejuvinate? For example would stem cell therapy help rejuvinate severely damaged/aged skin? Obviously UV exposure causes significant visible damage within just months or years of regular exposure particularly for people with fair skin.

Another thing to keep in mind is that just rejuvinating the skin will not effectively restore a youthful appearance. There are changes in fat deposits throughout the body such as additional fat forming under the eyes while the cheeks often lose their fat. The teeth undergo natural attrition from a lifetime of chewing even if one is not a bruxer. If they are lost completely it can cause a loss of bone reducing the vertical height of the lower 1/3 of the face. Also the ears seem to continue growing throughout life.

[BrandonFlorida]

I hope that this isn't perceived as too naive a question, but what factors account for the appearance of aged skin? Perhaps the answer to that is the same is the answer to aging in general.

I saw this study, PMID 16374460:
The Receptor for Advanced Glycation End Products Is Highly Expressed in the Skin and Upregulated by Advanced Glycation End Products and Tumor Necrosis Factor-Alpha (with a title like that, who needs to post an abstract ).

Is it a stretch to say that AGE accumulation in the skin is the primary cause of the characteristic appearance of skin of those in their eighties and older, or do DNA damage by UV light or shortening telomeres play the greater role?

Stephen

If this is a significant contributor to wrinkles, I wonder whether dietary sugar is a big factor. Before the settlement by Europeans of the New World, when sugar was still a delicacy for the rich, did people have fewer wrinkles? Diabetics don't really look similar to old people, do they?

[VictorBjoerk]

Do really diabetics tend to look older than their real age? I haven't noticed that.

[BrandonFlorida]

Do really diabetics tend to look older than their real age? I haven't noticed that.

If blood glucose is a causitive factor in crosslinking levels, and crosslinking is a significant contributor to the aging of tissue, shouldn't diabetics tend to look old?

[niner]

Do really diabetics tend to look older than their real age? I haven't noticed that.

If blood glucose is a causitive factor in crosslinking levels, and crosslinking is a significant contributor to the aging of tissue, shouldn't diabetics tend to look old?

This is a good question. A lot of diabetics are also overweight, and that would tend to disguise wrinkling. My uncle was a diabetic, and was also relatively thin, or at least normal weight. I remember him having a pretty wrinkly appearance, even though he was only in his late 40s or early 50s. He died in his early 50s of diabetic nephropathy. I have certainly heard diabetes referred to as a disease of premature aging. I don't know what the exact mix of factors is that contributes to the appearance of elderly skin, but I would like to know. I know that UV exposure is bad, and glycation is bad. There's also lipofuscin deposition, which shows up as age spots.

[VictorBjoerk]

so you should avoid antioxidant-rich juices if you want smooth skin? do the sugar in them outweigh the benefits of the antioxidants? I mean in juices like eg Tropicana antioxidants. since you shouldn't consume antioxidants by supplements and not from Juices with sugar, how should you obtain them???

[Ben]

so you should avoid antioxidant-rich juices if you want smooth skin? do the sugar in them outweigh the benefits of the antioxidants? I mean in juices like eg Tropicana antioxidants. since you shouldn't consume antioxidants by supplements and not from Juices with sugar, how should you obtain them???

There has been a lot of talk about juices. Basically they're too sweet and the juicing leaves behind a lot of what is healthy in the fruit such as the vitamins and fiber contained within the pulp or skin.

Fruit juices would especially lend themselves to cross linking because of the high amount of fructose.

[niner]

so you should avoid antioxidant-rich juices if you want smooth skin? do the sugar in them outweigh the benefits of the antioxidants? I mean in juices like eg Tropicana antioxidants. since you shouldn't consume antioxidants by supplements and not from Juices with sugar, how should you obtain them???

There has been a lot of talk about juices. Basically they're too sweet and the juicing leaves behind a lot of what is healthy in the fruit such as the vitamins and fiber contained within the pulp or skin.

Fruit juices would especially lend themselves to cross linking because of the high amount of fructose.

Ben is correct. Fructose is not your friend. You might consider berries, which tend to be lower in sugars. Shonghow, where did you hear that we shouldn't consume antioxidants by supplements? I do it all the time, although I've recently cut back on days that I exercise heavily.

BTW, one thing that really messes up your skin is cigarette smoking.

[Eva Victoria]

Do really diabetics tend to look older than their real age? I haven't noticed that.

If blood glucose is a causitive factor in crosslinking levels, and crosslinking is a significant contributor to the aging of tissue, shouldn't diabetics tend to look old?

This is a good question. A lot of diabetics are also overweight, and that would tend to disguise wrinkling. My uncle was a diabetic, and was also relatively thin, or at least normal weight. I remember him having a pretty wrinkly appearance, even though he was only in his late 40s or early 50s. He died in his early 50s of diabetic nephropathy. I have certainly heard diabetes referred to as a disease of premature aging. I don't know what the exact mix of factors is that contributes to the appearance of elderly skin, but I would like to know. I know that UV exposure is bad, and glycation is bad. There's also lipofuscin deposition, which shows up as age spots.

Contributing factors:

• UV exposure
• Cigarette smoke
• Pollution
• Loss of Sub-cutaneous fat
• Estrogen deficiency (in women)
• Thinning of the bones
• Dietary sugar
• Processed food
• Overcooked food
• Alcohol (spirit: oxidants) except wine (antioxidants)
• Psychological problems
• Change in sleep patterns (older people sleep less, contributing to faster aging)

What you can do:

• Use a high SPF/PPD photo stable (Euro) sunscreen daily (with Tinosorb M + S; AVO, Mexoryl SX+XL, TiO2, ZnO)
• Avoid cigarette smoke and pollution
• Eat well, don't be on diets on and off; eat regularly: ideally every 2-3 hours
• Take Estrogen supplements after the age of 50 with a supervision of a doctor!
• Avoid sugar in all forms
• Eat a lot of fresh leafy vegetables, fruits; poultry and fish, seeds and nuts. Eat moderate amount of carbs and meat.
• Be happy with your life, laugh a lot and look at life as something fun! Do at least one thing every day that makes you happy!
• Sleep enough, avoid late nights

Edited by Eva Victoria, 27 September 2008 - 04:55 PM.

[s123]

so you should avoid antioxidant-rich juices if you want smooth skin? do the sugar in them outweigh the benefits of the antioxidants? I mean in juices like eg Tropicana antioxidants. since you shouldn't consume antioxidants by supplements and not from Juices with sugar, how should you obtain them???

There has been a lot of talk about juices. Basically they're too sweet and the juicing leaves behind a lot of what is healthy in the fruit such as the vitamins and fiber contained within the pulp or skin.

Fruit juices would especially lend themselves to cross linking because of the high amount of fructose.

The most abundant AGE in skin is glucosepane which is formed from glucose and not fuctose. So, I don't think that frucose will be a major cause of skin aging. But fructose forms other AGEs that contributes to other kinds of aging.
1/5 of all the collagen molecules in old people are crosslinked by glucosepane and this increases to 1/2 in people with diabetes.

[sdxl]

Glycation does play an important role in skin aging.

Collagen glycation triggers the formation of aged skin in vitro.
Pageon H, Bakala H, Monnier VM, Asselineau D.

L'Oréal, Life Sciences, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy Cédex France. hpageon@rd.loreal.com

Glycation products accumulate during the aging of many slowly renewing tissues, including skin. We have developed an in vitro model of chronologic aging of skin based on reconstructed skin modified by artificially glycating the collagen used to prepare the dermal compartment. The morphology of the modified skin is close to the morphology usually observed except that the dermis is altered in its fibrillar structure. Moreover, the analysis of skin markers revealed several unexpected biological and morphological modifications, which reflect in vivo aging and could be related to glycation per se. These include the activation of fibroblasts, increase of matrix molecules (collagen type III and collagen type IV) and metalloproteinase production (MMP1, MMP2 and MMP9), thickening of the basement membrane zone, and more strikingly, the modification of alpha6 and beta1 integrin patterns especially in epidermis, in a way closely resembling aged skin in vivo. We also found that these effects could be related to the production of putative diffusible factors by the dermal fibroblasts activated by glycation. Finally, we show that all these effects are likely to be glycation specific since they could be inhibited by aminoguanidine, a well-known glycation inhibitor. We conclude that the reconstructed skin model modified by glycation of the collagen closely mimics chronologic aging of skin in vivo. Taken together, these results strengthen the importance of glycation reactions in skin aging.

There are more studies like this.

[BrandonFlorida]

Glycation does play an important role in skin aging.

Collagen glycation triggers the formation of aged skin in vitro.
Pageon H, Bakala H, Monnier VM, Asselineau D.

L'Oréal, Life Sciences, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy Cédex France. hpageon@rd.loreal.com

Glycation products accumulate during the aging of many slowly renewing tissues, including skin. We have developed an in vitro model of chronologic aging of skin based on reconstructed skin modified by artificially glycating the collagen used to prepare the dermal compartment. The morphology of the modified skin is close to the morphology usually observed except that the dermis is altered in its fibrillar structure. Moreover, the analysis of skin markers revealed several unexpected biological and morphological modifications, which reflect in vivo aging and could be related to glycation per se. These include the activation of fibroblasts, increase of matrix molecules (collagen type III and collagen type IV) and metalloproteinase production (MMP1, MMP2 and MMP9), thickening of the basement membrane zone, and more strikingly, the modification of alpha6 and beta1 integrin patterns especially in epidermis, in a way closely resembling aged skin in vivo. We also found that these effects could be related to the production of putative diffusible factors by the dermal fibroblasts activated by glycation. Finally, we show that all these effects are likely to be glycation specific since they could be inhibited by aminoguanidine, a well-known glycation inhibitor. We conclude that the reconstructed skin model modified by glycation of the collagen closely mimics chronologic aging of skin in vivo. Taken together, these results strengthen the importance of glycation reactions in skin aging.

There are more studies like this.

Thank you. This is very interesting, although I wish I understood it better. I get the drift, though.

[BrandonFlorida]

Glycation does play an important role in skin aging.

Collagen glycation triggers the formation of aged skin in vitro.
Pageon H, Bakala H, Monnier VM, Asselineau D.

L'Oréal, Life Sciences, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy Cédex France. hpageon@rd.loreal.com

Glycation products accumulate during the aging of many slowly renewing tissues, including skin. We have developed an in vitro model of chronologic aging of skin based on reconstructed skin modified by artificially glycating the collagen used to prepare the dermal compartment. The morphology of the modified skin is close to the morphology usually observed except that the dermis is altered in its fibrillar structure. Moreover, the analysis of skin markers revealed several unexpected biological and morphological modifications, which reflect in vivo aging and could be related to glycation per se. These include the activation of fibroblasts, increase of matrix molecules (collagen type III and collagen type IV) and metalloproteinase production (MMP1, MMP2 and MMP9), thickening of the basement membrane zone, and more strikingly, the modification of alpha6 and beta1 integrin patterns especially in epidermis, in a way closely resembling aged skin in vivo. We also found that these effects could be related to the production of putative diffusible factors by the dermal fibroblasts activated by glycation. Finally, we show that all these effects are likely to be glycation specific since they could be inhibited by aminoguanidine, a well-known glycation inhibitor. We conclude that the reconstructed skin model modified by glycation of the collagen closely mimics chronologic aging of skin in vivo. Taken together, these results strengthen the importance of glycation reactions in skin aging.

There are more studies like this.

Another abstract by the same people:

Exp Gerontol. 2008 Apr 7; : 18485649 (P,S,G,E,B,D) Reconstructed skin modified by glycation of the dermal equivalent as a model for skin aging and its potential use to evaluate anti-glycation molecules.

Hervé Pageon, Marie-Pascale Técher, Daniel Asselineau L'Oréal, Life Sciences Advanced Research, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy, France.

Glycation is a slow chemical reaction which takes place between amino residues in protein and a reducing sugar. In skin this reaction creates new residues or induces the formation of cross-links (advanced glycation end products or AGEs) in the extracellular matrix of the dermis. Formation of such cross-links between macromolecules may be responsible for loss of elasticity or modification of other properties of the dermis observed during aging. We had previously developed a reconstructed skin model which enabled us to study the consequences of matrix alteration by preglycation of the collagen and have reported several modifications of interest induced by glycation in the dermal and epidermal compartments of reconstructed skin as well as at the level of the dermal-epidermal junction. For example we showed that collagen IV and laminin were increased in the basement membrane zone and that alpha6 and beta1 integrins in epidermis were expanded to suprabasal layers. The aim of this new study was to look at the biological effects of glycation inhibitors like aminoguanidine in the skin model. Aminoguanidine was mixed with collagen in the presence of ribose as reducing sugar, and immunostaining was used to visualize its effects on AGE Products and biological markers. After aminoguanidine treatment, we found a low amount of AGE products and a possible return to the normal pattern of distribution of markers in skin constructs as compared to those treated with ribose only. Interestingly similar results were also obtained, although to a lesser extent, with a blueberry extract. In conclusion the glycation inhibitory effect has been functionally demonstrated in the reconstructed skin model and it is shown that this model can be used to assess anti-glycation agents.

Edited by BrandonFlorida, 29 September 2008 - 10:06 PM.

[Ben]

so you should avoid antioxidant-rich juices if you want smooth skin? do the sugar in them outweigh the benefits of the antioxidants? I mean in juices like eg Tropicana antioxidants. since you shouldn't consume antioxidants by supplements and not from Juices with sugar, how should you obtain them???

There has been a lot of talk about juices. Basically they're too sweet and the juicing leaves behind a lot of what is healthy in the fruit such as the vitamins and fiber contained within the pulp or skin.

Fruit juices would especially lend themselves to cross linking because of the high amount of fructose.

The most abundant AGE in skin is glucosepane which is formed from glucose and not fuctose. So, I don't think that frucose will be a major cause of skin aging. But fructose forms other AGEs that contributes to other kinds of aging.
1/5 of all the collagen molecules in old people are crosslinked by glucosepane and this increases to 1/2 in people with diabetes.

Woah those are some amazing figures! Half in diabetics, crazy. Where did they come from, may I ask?

[Johan]

The most abundant AGE in skin is glucosepane which is formed from glucose and not fuctose. So, I don't think that frucose will be a major cause of skin aging. But fructose forms other AGEs that contributes to other kinds of aging.
1/5 of all the collagen molecules in old people are crosslinked by glucosepane and this increases to 1/2 in people with diabetes.

Woah those are some amazing figures! Half in diabetics, crazy. Where did they come from, may I ask?

Here is the paper in which those numbers are found:

Attached Files

•  Glucosepane_Is_a_Major_Protein_Cross_link_of_the_Senescent_Human_Extracellular_Matrix.pdf   420.37KB   67 downloads

Edited by Johan, 01 October 2008 - 09:52 AM.

[VictorBjoerk]

how can you see the difference in the skin between someone who has a lot of glycation damage vs someone with little glycation damage and lots of UV damage?

[Ben]

The most abundant AGE in skin is glucosepane which is formed from glucose and not fuctose. So, I don't think that frucose will be a major cause of skin aging. But fructose forms other AGEs that contributes to other kinds of aging.
1/5 of all the collagen molecules in old people are crosslinked by glucosepane and this increases to 1/2 in people with diabetes.

Woah those are some amazing figures! Half in diabetics, crazy. Where did they come from, may I ask?

Here is the paper in which those numbers are found:

That was very quick! :D! Thanks a lot.

[Fredrik]

Exp Gerontol. 2008 Apr 7; : 18485649 (P,S,G,E,B,D) Reconstructed skin modified by glycation of the dermal equivalent as a model for skin aging and its potential use to evaluate anti-glycation molecules.

Hervé Pageon, Marie-Pascale Técher, Daniel Asselineau L'Oréal, Life Sciences Advanced Research, Centre Charles Zviak, 90 rue du Général Roguet, 92583 Clichy, France.

Glycation is a slow chemical reaction which takes place between amino residues in protein and a reducing sugar. In skin this reaction creates new residues or induces the formation of cross-links (advanced glycation end products or AGEs) in the extracellular matrix of the dermis. Formation of such cross-links between macromolecules may be responsible for loss of elasticity or modification of other properties of the dermis observed during aging. We had previously developed a reconstructed skin model which enabled us to study the consequences of matrix alteration by preglycation of the collagen and have reported several modifications of interest induced by glycation in the dermal and epidermal compartments of reconstructed skin as well as at the level of the dermal-epidermal junction. For example we showed that collagen IV and laminin were increased in the basement membrane zone and that alpha6 and beta1 integrins in epidermis were expanded to suprabasal layers. The aim of this new study was to look at the biological effects of glycation inhibitors like aminoguanidine in the skin model. Aminoguanidine was mixed with collagen in the presence of ribose as reducing sugar, and immunostaining was used to visualize its effects on AGE Products and biological markers. After aminoguanidine treatment, we found a low amount of AGE products and a possible return to the normal pattern of distribution of markers in skin constructs as compared to those treated with ribose only. Interestingly similar results were also obtained, although to a lesser extent, with a blueberry extract. In conclusion the glycation inhibitory effect has been functionally demonstrated in the reconstructed skin model and it is shown that this model can be used to assess anti-glycation agents.

I did some detective work (googling that is) and here is the commercial result of the above L'Oréal research on anti-glycation agents: Skinceuticals (L'Oréal) new "A.G.E. Interrupter" with 4% blueberry extract and 30% (!) "Pro-xylane". Who knows if these two ingredients work, since there´s no published studies on this cream yet, just lab work with pure ingredients on reconstructed skin. But if this works then it would be a perfect addition to a collagen and elastin regenerating regime since the three major molecules in skin are collagen, elastin and hyaluronic acid.



http://www.treatment...nterrupter.html


The patent description: "Use of an extract of at least one vaccinium-type plant as an anti-glycation agent"

http://www.patentsto...8/fulltext.html


Pro-xylane is the TM name of their patented glycosaminoglycan (GAG) stimulating xylose-derivative (my eye cream I´m test driving has 5%). GAGs can bind 1000 time their weight in water and are natural constituents of skin.

A bit about their "Pro-xylane" molecule and what it supposedly does, at least to aged atrophic skin:

http://www.timesonli...ticle690392.ece


and from Pubmed:

A new C-xylopyranoside derivative induces skin expression of glycosaminoglycans and heparan sulphate proteoglycans.

Pineau N, Bernerd F, Cavezza A, Dalko-Csiba M, Breton L. L'Oréal Recherche, 90 rue du Général Roguet, 92583 Clichy cedex, France. npineau@rd.loreal.com

Severe structural changes, including deterioration of the mechanical properties of the dermis, occur during skin aging. It is well known that the degradation of the extracellular matrix contributes to the physical changes in aged skin. Whereas many studies have been devoted to age-related alterations of collagen fibrils, far less attention has been paid to another major family of extracellular matrix components, the glycosaminoglycans (GAGs) and proteoglycans (PGs). Heparan sulphate-proteoglycans, (HS-PGs), a subclass of the PG family that decreases during aging, regulate proliferation and proteolysis as well as matrix adhesion and assembly, and thus, may have important functions in skin. These PGs may represent important targets for dermo-cosmetology in fighting skin aging. The purpose of this study was to demonstrate the potential of a new C-xylopyranoside derivative (C-beta-D-xylopyranoside-2-hydroxy-propane simplified as C-Xyloside) to improve HS-PGs expression in human skin. In an organotypical model of corticosteroid atrophic human skin, characterized by a decrease of PGs expression, treatment with C-Xyloside improved expression of HS-PGs.

PMID: 18086587

Edited by Fredrik, 03 October 2008 - 03:27 PM.