Renovage induces heat shock proteins, not telomerase. This is not DNA repair. This is bogus. | BareFacedTruth.com

Renovage induces heat shock proteins, not telomerase. This is not DNA repair. This is bogus.

This is the first of a series of posts dealing with so-called “DNA serum”.

One of our favorite product review (selling) sites is currently  recommending a product  (Osmotics Renovage Cellular Longevity Serum, $150) whose active ingredient is Teprenone.  Their “scientific” review claims that the product “stabilizes telomeres”.  Very interesting, because when you go to the Sederma site and track down the (unpublished) studies to support this claim, you find nada, nothing. Instead what you find is a study in which fibroblasts in culture given Teprenone lived longer (as a colony) than untreated fibroblasts. From which they infer that it has something to do with telomeres  (the basis of a popular theory about aging). The problem (and there are many) is that they didn’t bother to actually look at telomeres. They just built an assumption upon an assumption, then added some more assumptions. Then they built a marketing message on top of that.

In culture (in vitro, in the lab) there are a lot of things that influence the life span of fibroblast cells. Donor characteristics, sampling site, culture conditions, media used, temperature, etc, etc. There are literally hundreds of things you can do to a fibroblast culture to make it “live longer”. Add chemicals that slow down metabolism. Lower the temperature of the incubator. Change the oxygen concentration. Add an antioxidant. Many, many things. All of this means nothing in terms of life span of cells in in your body (in vivo). Why? Because in your body, fibroblasts are “never required to make as many divisions as they do in vitro” (from Littlefield, a classic textbook out of Harvard).  And why is that? Because new fibroblasts are made (from stem cells) to replace them long before they reach their limit. And why would the body do that? Kill off perfectly good cells before they have exhausted their ability to replicate? Because the longer cells have been around, the more prone they are to DNA mutations (e.g. cancer). It’s a good strategy.

Had the reviewer in question looked more closely, she might have discovered that Teprenone (the active ingredient) is a trade name for geranylgeranylacetone – a drug approved  in Japan to treat gastric ulcers. It was rejected by the FDA in this country and remains unapproved.

Geranylgeranylacetone is a very potent chemical that induces naturally made molecules inside cells (from bacteria to human) called heat shock proteins (HSP’s). It effects several classes of these, including HSP 70 and 90 families. The stress-inducible chaperone heat shock protein (HSP) 70 is considered a danger signal if released into the extracellular environment. It has been proposed to play a role in the pathogenesis of skin diseases such as psoriasis and lupus erythematosus (Exp Dermatol. 2011 Aug;20(8):637-41). Hsp70  has been found to act as a recognition structure for natural killer (NK) cells in the body. (Int J Hyperthermia. 2009 May;25(3):169-75.).  Cells transformed by Hsp70 are tagged as senescent and targeted for destruction by our indwelling immune system assassins, killer T cells.

Geranylgeranylacetone induces apoptosis (programmed cell death) and cell cycle arrest as well as cell growth inhibition  (Oncogene. 2001 May 24;20(23):2927-36).  This is quite likely why it slows down fibroblasts in culture (prolonging their life, by making them a lot less active).  This drug may have anti-cancer effects for these very reasons. But as an anti-aging strategy, it lacks logic. Even if it does make fibroblasts in the skin live longer, it slows down the production of matrix proteins (like collagen) which would accelerate the signs of aging.

Heat shock proteins are of great interest to cell biologists, and clearly can have a protective effect against cell damage (e.g. gastric epithelial cells). But the particular HSP’s that Teprenone induce are not the ones that are likely to benefit skin. There are, in fact, other unrelated compounds under investigation that prevent and reverse DNA damage due to solar irradiation (the principle kind of stress that skin has to deal with). We will be talking about that good news in a post coming soon.

Summary: the company that sells teprenone as an active for skin care wants you to think it does good things for DNA and telomeres (the ends of DNA strands that have to do with programmed cell death). This claim is bogus. It appears they never even measured telomeres. What Teprenone actually does is induce heat shock proteins. These are powerful natural cellular messaging chemicals. Released under the wrong circumstances, these signals could be harmful, accelerating rather than retarding the visible signs of aging over time.  Online anti-aging review sites that pretend to understand science are believing this marketing hype, and are then misleading you as they induce you to buy this stuff from their site.

 

48 Comments

  1. ChicGeek says:

    Thanks for this! I’d already given EGF a pass–under the assumption that, “if it works, it’s really bad idea,” but I hadn’t yet looked into teprenone.

    I’d like to note that it is the manufacturer of Renovage itself that makes the telomere claims. Osmotics is repeating them.

    • drjohn says:

      Hi ChG, True, but Osmotics claims this on their web site: OSMOTICS works with leading university medical centers, world-renowned scientists and our own scientific advisory panel to incorporate the latest breakthroughs and most advanced thinking in this exciting new field. . Now let me officially invite any of those world-renowned scientists they consult with to contact us. We remain open to all scientific debate. They want to dispute any of this, let’s hear from them. If they remain silent, we will assume they don’t exist or never were asked to look at this stuff. If any real scientists had been involved, they would have at a minimum thrown in a few caveats about this little bundle of dynamite. Now, since TIA claims to dispense “the honest truth about beauty & personal care products” then there must also be some minimum standard of scientific rigor applied to them also. Passing along bogus claims is not what I would expect from “truth in anything“.

  2. ChicGeek says:

    All those nameless scientists and universities…. 😛 Almost as frequently cited as the phrase “doctor-approved.”

    When you get to a larger company, marketing is a beast of its own and has very little contact with any other department. They write what sounds good. Its relationship to truth is all too often accidental. And I can guarantee they would NEVER have any scientist review their ad copy. It generally works like this: Get a few sound bites from the “scientific panel.” Spin them in a way that makes them sound the best. Run it by legal to see if you’re likely to get red-flagged by the FDA. Publish it.

    There are precious few companies that don’t do this. I wish there were more.

  3. Christallin says:

    The price is the main red flag not to put any stock in this stuff. Huge price is overcompensation for a perceived lack. If it has all this so called research etc. behind it, why isn’t it available by prescription with a $5.00 copay. Give me a break.

  4. lyonella says:

    Jumping ahead: what sunscreen do you recommend?

    • drjohn says:

      Dr. George is our UV battling superhero. I’ll let him give you some ideas. I’m Canadian so I don’t need sunscreen. Keep the hood up on my parka year round. Of course the people here in so cal look askance at me.

  5. Dennyjune says:

    Finally I have found a website with the real truth. Please please stay pure. I am eternally grateful for your time and effort.

  6. lyonella says:

    LOL.. ok! Ill wait to see what DrGeorge says then! =)

  7. Drgeorge says:

    I am working on a post that will discuss sun protection in some detail including new regulations about what is required to be disclosed by the FDA. Watch for it.

    Meawhile, know that there are three basic types of products to protect the skin for sun exposure.:1) sunscreens which use a chemical that absorbs (and often scatters) UV light at certain wavelengths; 2) sunblocks which use physical paticles or “barriers “to block, disperse, and reflect UV light; 3) and combinations of the two.

    The market is filled with effective products on one sort or another. What has gotten scrutiny in recent years are claims of SPF protection, duration of protection without reapplication, and resistence to water or persipiration. Additioanl ingredients in products account for some of the major differrences in quality and price. Antioxidants, moisturizers, and lubricants are examples.

    A higher end product of the combination type is by Epicuren and contains 10% zinc oxide (physical barrier) and 7.5% octyl methosycinnamate (UV “absorbant”). Sun protection products vary from quite inexpensive to expensive.

    What should be remembered is there is no apply once and forget it type product if one spends all day in the sun or is involved in water sports.

    • lyonella says:

      Im concerned about chemical SS ingredients breaking down in UV light and contributing to ROS damage, while zinc oxide is more stable and can be used at high % if micronized or nano sized and be sheer on the skin. What do you think Dr George?

  8. NGP says:

    Hi Dr J

    Nice article, thanks for writing this. But I’m a little puzzled by a study done on laser skin rejuvenation which theorized that HSPs created by lasers were responsible for increased collagen production. Can you read this study and explain why HSPs from lasers are beneficial while the HSPs from Teprenone are detrimental to the skin? Here the link to the article I read a long time ago: http://www.sciencedaily.com/releases/2010/10/101021141000.htm

    • drjohn says:

      You ask a very good, but very complicated question. I’ll try to do it justice in a paragraph, but we may need to go even deeper to gain full understanding.

      Heat shock proteins (there are about a a dozen) respond to cellular stress with strategies to help cell survival. Hormesis as a principle states that repeated stresses can help cells to respond to damage later on. Sort of like fire drills for the cell. That’s a good general principle, and it works in many experimental paradigms. Heat shock proteins are part of that response. But there is a bifurcated strategy cells use — one is apoptosis (cell death by immune cells) which HSP’s reduce. The other is autophagy (cell suicide, literally eating itself). Turns out that HSP’s decrease the former but increase the latter.

      Now, also keep in mind that these cells are not really damaged, they are being fooled into thinking they are (by geranylgeranylacetone). They do things like shut down some protein production by DNA (they assume the DNA is damaged). They alter intracellular protein dynamics. Several organelles are affected., including mitochondria. Basically these cells are in hunker down mode. Chronic exposure to geranylgeranylacetone will mean they are in this mode most of the time. Life for the cell never quite gets back to normal. It’s a “stress” to be sure. And some end up eating themselves (for the good of the neighborhood).

      Collagen production can be increased by damage. Including cell burning (heat). But there is real damage. Cells will die. Stem cells will come to the rescue, and coordinate healing. Cytokines will pour forth. However, as age advances, the system starts to get less efficient. Fewer stem cells to respond. The response becomes more inflammatory. Inflammatory healing leads to more scarring, less elasticity. The tissues priority becomes more about survival than about growth and prosperity. Procollagen proteins are produced urgently, but what is the extracellular environment like? Is this collagen rebuilding, or just defensive output of anything into the matrix to protect the cell from unkown (perceived) invaders?

      Maybe at the cellular level, there is a military or emergency response analogy. HSP’s are the cell’s DEFCON level 5. Death threats, incoming missiles on the radar. Shut down the factories, prepare for war. Certain cytokine patterns can also mimic an emergency response, but it is more of a DEFCON level 1 or 2. Got some damage here, but under control sir, we can handle it. No threat to life. But, while we have the construction guys here, why don’t we do some remodeling?

  9. NGP says:

    Thanks for the explanation. I have read about hormesis and practice it to help keep my body functioning better. I’m over 50 but have no aches/pains, take no meds, and have excellent health. I do hormetic activities like sprinting to exhaustion 3 times a week for just 20 minutes, intermittent 18 hour fasting once a week, cold showers (hate those). It’s basically very “controlled” stress. Hormesis is biphasic (I think that’s the term). A little stress is good to build the body’s natural defenses (increase HGF) and stamina, but constant stress or overdosing of something can be very damaging or detrimental. You see that biphasic quality in a lot of pharmaceuticals. I think the thing about Teprenone, like you said, is that you are putting your skin under continual stress mode there, not good for the long run health of your skin.. The heat induced collagen regeneration from laser is a good thing but you probably don’t want to be doing that on a continual basis. Especially the older you are you, and more importantly you need to provide the skin with the building blocks to make good quality collagen, through diet, exercise, antioxidants, increased skin’metabolism. So, it all makes sense now. Thanks again

  10. NGP says:

    OK, another question pops up as to why Teprenone which IS classified as a drug in Japan and should be classified as a drug in the U.S. because it obviously affects cellular function and has potentially harmful consequences, ever got into “cosmetic” products and even sold as a unregulated substance in many DIY sites like Lotioncrafters. How did the mfgr of Teprenone (Sederma) manage to do that? It’s a drug AND a cosmetic ingredient? They seemed to beat the system somehow with this one. Even Retin-A is regulated. Makes me wonder how many other skincare ingredients have an ugly side to them we don’t know about. We are, for the most part, guinea pigs for these products that have no independent studies, no toxicity studies, or valid clinical trials behind them. The gov’t is not watching out for us as far as cosmetics go. It’s pretty much a self-regulated industry. You are trusting the word of the manufacturer, who has a definite stake in making sure you are kept in the dark. If not for informed people such as you and Dr G, we’d never know about the negatives of using this stuff. Unfortunately, I think most scientists don’t have the time or resources to educate the public about such things.. So, again thank you for doing this blog. There are a lot of people who want to understand this stuff and make informed decisions.

  11. Miss Wisteria says:

    I am using the Dna serum (renovage) from NCN that i got since a few days. I got scared after reading about the product on your site. Do you think it’s best to stop using the product? Will it do more damage than good? For now, after a few days of usage, my skin looks better than ever, so it’ a shame to hear such things about something that works so good (for now)…

    • drjohn says:

      So many products make your skin feel great after a few days. It’s always exciting to try something new, and the anticipation alone gears you up for a positive experience. The first few days of any new product experience is all about the look, feel, and smell. The texture, the creaminess. If a product contains moisturizers, your skin may drink it up and feel refreshed. Now if this is all you are looking for in a product, then I would strongly suggest you think about any one of a number of products by the big companies that sell at Target & the grocery store for under $40. They can do that pretty well. If you are paying over $100 for a product, you should be expecting more: true anti-aging benefits. But you won’t experience these in a few days. It takes months for regeneration to take effect in your skin’s collagen & elastin fibers.

      On to your question about Renovage with Teprenone. We haven’t tested Renovage and so we don’t know if it is unsafe. All we know is that Teprenone is an anti-ulcer drug that induces certain heat shock proteins, and is totally unproven to do anything good for skin. We know the claims based on science are bogus. But, you know what? It may be there in insignificant quantities, and it may not even be getting absorbed. Sometimes skin care product companies put something in a product, often in miniscule amounts, for marketing purposes only not really expecting it to have an effect. This allows them to tell a story (in some cases pure fiction) that they think will convince people to buy their product. The makers don’t tell us how much is in this product. For all we know, it could be safe for any of these reasons. But I guess I have trouble trusting any company who would thumb their noses at real science and/or be deceitful with customers in the first place. Maybe the makers will come here, or to one of the online forums, and answer all these questions for us. Thus far, they have declined to do so. I wonder why?

      In the end, it is all about personal choice. Out goal here is to equip you to make better choices as a skin care product consumer, but not to decide for you. You should look around around at all *reliable* sources of information. In the end, it is your body, your skin, and your decision to make. We care about the truth, we care about our readers. We want the very best for you as you explore the world of skin care.

  12. Rachael says:

    Hi there,
    What can you tell me about the skincare products and supplements from jeunesse global?
    They claim to be actual scientists manufacturing skincare. They apparently harvest human stem cells from human fat cells for their serum. (your probably laughing already right?)
    Would you be so kind as to check out their website & products and report back?
    jeunessglobal.com

    Thanks
    Rachael

    • drjohn says:

      Hi Rachel. You are talking about the amazing scientific team of Randy Ray and Wendy Lewis. These are notorious multilevel marketers who have been in and out of various schemes for decades. As soon as the pyramid gets to the point where the “little people” at the bottom have shelled out their past few pennies based on the promise they will become millionaires (selling their product), they move on to the next “opportunity”. Here is your high science duo in action: http://www.flickr.com/photos/ecoteambr/3099570998/. You be the judge.

      This product claims to contain adipose stem cell conditioned medium, and appears to be related to a Korean company that has been on that bandwagon for years. But then it seems to contain it in very small quantities (way down the ingredients list) and contains a bunch of other actives with claims that are clearly specious. “Stops telomere shortening”, that sort of hocus pocus. My opinion? Stay away from any company whose menu is filled with things like “opportunity”. It is spelled MLM. In my opinion, if you have to resort to trickery like that to sell products, you must not have very good products.

      On the issue of adipose tissue derived stem cells, they can be used to farm cytokines (as could just about kind of cell theoretically), but the cytokine pattern may not be all that helpful to aging skin. Wrong stem cell “niche”. Fat is not where the body’s “911” repair & rejuvenate stem cells live; those reside principally from bone marrow. While they may share the same stem cell markers, they are phenotypically different. Different role and agenda (ready to make more fat cells, as needed).

  13. MJ says:

    I agree with everything you write, excepting that, probably as a result of jack a$$ luck, they may be correct in assuming that the cultures are living longer as a result of telomere lengthening, or slowed loss. I am expert in telomerase incubation and a big problem that some cells have, which prevents them from producing telomerase, is an absence of HSP 90. The addition of HSP 90 is helpful in producing processive telomerase in non-human cells, so maybe there is a little bit of truth to their claims. Just saying maybe.

    • drjohn says:

      Thanks for your thoughts on this. I do get it about HSP 90 being a molecular chaperone for many proteins, including telomerase, under physiologic circumstances. And that blocking HSP90 could cause problems with many proteins, including telomerase. But when it comes to putting the HSP system into chronic overdrive with daily doses on an inducer, I start to think of the cascade of intracellular stresses that induces, and can’t help thinking I am being asked to take a leap of faith that it is net beneficial. In vivo putting HSP90 into overdrive also promotes apoptosis in many tissues. What’s that about.? And how does this help skin again? Swiss cheese theories of regeneration.

  14. CuriousGirl says:

    i am a bit concerned with these stem cell conditioned media based products available in the market. Don’t these guys need any FDA approval or registration with similar regulatory bodies that can keep a check on the safety of their products?

    • drjohn says:

      Yes, the FDA does regulate cosmetics (also called cosmeceuticals). . Pre-market approval is not required, but there are various regulations, especially governing manufacturing, labeling, and the like, with an emphasis on safety.

  15. Susan says:

    I am posting this article which I wrote for my clients. However, it is related to the concerns about telomeres and cell death as mentioned in this post. Let me know if this explanation relieves concerns about telomeres. Thank you.

    Exfoliation and the Hayflick Limit
    Question: Is it true that too much exfoliation can make you ‘run out of skin’ due to the Hayflick limit?
    The Hayflick limit predicts that some cells have a finite ability to regenerate–up to 50 times before they die off. However, the Hayflick limit only applies to differentiated cells as opposed to undifferentiated cells such as stem cells. It is important to remember that the Hayflick limit applies only to differentiated cells, such as keratinocytes and their final stage, corneocytes, which are cells that have matured to fulfill their final function. It does not apply to stem cells which are not differentiated to meet a specific function. Epidermal stem cells—unaffected by the Hayflick limit—will regenerate for the life of the organism, continuing to differentiate into corneocytes when signaled to do so. Removal of corneocytes by exfoliation is one of those signals.
    Thus the real question is: If the Hayflick limit applies only to differentiated cells such as keratinocytes and corneocytes, then why isn’t there is a limit to the number of times these cells regenerate? And if this limit is reached, will exfoliation thin rather than replenish the skin?
    Answer: Even though it may seem logical to conclude that if corneocytes, the cells removed upon exfoliation, are subject to the Hayflick limit, then exfoliation will thin the skin. However, this conclusion ignores the unique feature of keratinocytes—they do not regenerate. They are designed to die off cyclically, about every 35 days, a cycle which slows down with aging. Exfoliation speeds up that cycle by the removal of corneocytes, signaling the formation of newer replacements. Thus, a new layer of younger, healthier skin emerges. If this were not so, then there would be a limit to our body’s ability to heal wounds by regenerating new cells and the corneocytes that protect them.
    Bottom line: Corneocytes are not affected by the Hayflick limit because they have already reached their regenerative limit. Once they are removed by exfoliation or slough off naturally, they are replaced by new corneocytes that have emerged from the epidermal stem cells, which are not affected by the Hayflick limit. Thus, exfoliate frequently—even daily depending on the method. It will not cause you to ‘run out of skin.’

    Susan Nathan, LE, B.S. Microbiology

    • drjohn says:

      You make some excellent points.

      We would tend to agree that the Hayflick limit is often misapplied. It relates to replicative senescence (RA), not to Stress-Induced Premature Senescence (SIPS) which is more the problem with skin. Chronic stresses can cause cells to undergo senescence, and their phenotype is altered, and they start producing inflammatory cytokines. They age, and they look aged. The Hayflick limit is at its core not an hypothesis about aging, but about cancer genesis.

      But stem cells are not an inexhaustible supply of precursors to skin cells, or any cell. They to can undergo stress, are subject to RA, and SIPS, and are not immortal. Their DNA can be damaged, their telomeres shortened. They age also.

      So here is an interesting question. If we speed up skin turnover with frequent exfoliation, are we making stem cells (e.g. in bone marrow) work harder in order to have to resupply lost skin cell precursors? Is that stressful, and if so a good stress or a bad one? There is no answer yet.

      The most promising strategy to cure aging is to stimulate the body’s own regenerative capacities, to “tell” the body not to age. True in skin. Signal it with youthful cytokines & growth factors. Take away the chronic stressors (wear sunblock, eat foods with antioxidants, avoid topical Nerium oleander). Cell level epigenetic preprogramming.

      By the way, we are most impressed with the quality of scientific thought brought here by Susan, who is an esthetician with a science background in Chino, CA. If you live in the area, look her up. http://bornagainskin.com

  16. Pam says:

    I recently found this website and love reading the articles and posts. You have helped me make sense out of the skin care “failures” I have experienced for years. I’ve spent a TON of money on very expensive and worthless products that produced no anti-aging results at all. All this time I thought maybe I just had uniquely stubborn skin……

  17. drjohn says:

    Heat shock proteins are highly inflammatory, and are associated with the body’s emergency responses to trauma, infection, etc. . If the people making this “claim” knew even just the basics of medicine and physiology, they would understand that they are describing a pathogenic process. HSP47 is part of the cascade that creates fibrosis. Fibrotic tissue is like scar tissue. If it happens in the kidney, or lung, it will kill you (HSP47 is highly associated with those fibrotic diseases). If it happens in the skin, fibrosis leads to gnarly collagen cross links, loss of elasticity, and stiffening. Read this post about fibrosis to complete the picture. Its called scleroderma when the face becomes fibrotic.

    Folks, we are not making this stuff up. Just go to Pubmed and search on “heat shock protein 47”. You will discover that it is an inflammatory cytokine. Associated with liver fibrosis and indeed fibrosis anywhere in the body. Now when you laser skin it kills cells by heating up the tissue, causing HSP’s to upregulate. Then the body responds (e.g. via stem cells) to counter that inflammation and heal with a good aesthetic outcome. But suppose you were to laser your face daily? never allow it to move from inflammation to anti-inflammation. Result? Scarring and fibrosis. And yet, these folks are advocating you do just that on your skin’s epidermis. Create a chronic inflammation. Good for skin? I don’t think so. In fact our work proves that bone marrow derived mesenchymal stem cells do some of their magic by suppressing these inflammatory cytokines. Works to stop heart attacks and stokes, and works to prevent skinflammaging.

    Now, in truth I think that the vast majority of so-called peptides are a bunch of hokum anyway (even the name bugs me since peptides are merely small proteins, which the vast majority of skin molecules are – so it doesn’t tell you much. Which is probably the point). You can get fibroblasts in culture to grow simply by speaking in cross tones. We need to do a whole post on the underwhelming evidence for most peptides. Our learned colleagues in dermatology and plastic surgery agree on this point.

  18. Mrs. Baker says:

    I’d like to ask one of the doctors here what their thoughts are concerning Ultherapy facial treatments? Work? Safe? Long term effects real? Thank you in advance for your expertise. I am looking into this (anti-aging treatment to look younger around eyes & jawline/neck).

    • drjohn says:

      Ultherapy is a bit outdated. I would suggest looking into more modern instruments like Venus Freeze, etc. The heat is better controlled (fractional) to minimize bad effects.

  19. Naita says:

    Hi, Thank you for this excellent site!! Can you please name some of your favorite product review (selling) sites? its a jungle out there, so it would be nice to know some ok reliable sites when bying products:-)

    • drjohn says:

      Probably best to avoid sites that are reviewing and selling products in the same place. Truth-in-Aging is a prime example of an online site doing that and they consistently get the science all wrong. And we have seen examples of how they will ignore their own reviewers opinions in order to sell products in stock. Shameful! We like Paula Begoun (http://www.paulaschoice.com/beautypedia/) even though there is selling going on nearby – it seems that the science editorial and selling is disconnected. Obviously a thoughtful staff there. Bulletin boards like EDS are good for gaining lots of user experience opinions. Among the beauty magazines, and even the industry rags, we see most of them getting the science wrong most of the time – mainly because there are so many “experts” (including doctors and guys pretending to be doctors) that are feeding them incorrect information. Sad. The best of that fashion/beauty mag bunch seems to be NewYou (http://www.newyou.com) who actually carefully research their articles. Bravo!

  20. Missy says:

    Dr John, following from my most recent post, my friend just informed me USA Juenesse site shows cytokines on ingredients, but Australia site ( me) does not.

  21. Indy says:

    Well, I have been looking something for my husband for his dark circles and bags underneath the eyes.I just can’t find anything right.Please help.

    • drjohn says:

      Under the eye skin is thin and prone to sun damage, and is loosely attached such that it has “capacity” to hold water (edema). It is more prone to sensitivities to soap and chemicals. People often rub around their eyes (when tired) causing minor stresses. Hyperpigmentation (darkening) happens wherever skin is inflamed, and all these things cause inflammation. The best strategy is to “uninflame”. Creams with oils and emollients help, but especially look for anti-inflammatory natural ingredients. Retinoids help, but the doses must be just right or flaking and dryness can make the issues worse. Brighteners including vitamin C, alpha arbutin, kojic acid, and others can help. Sunscreens are critical. Anti-inflammatory cytokines and growth factors (e.g. TGF-B3, IGF-1, IGF-2, and KGF) are the leading edge and work by regenerating skin while also toning down inflammation and creating/opening up channels for water to flow away. Hope this helps.

  22. Abby says:

    Oh wow, thanks for informing us about Renovage you have saved me from a serious mistake!
    What do you think about metrixyl 3000? I am especially concerned about the type of collagen that it is promoting, is it the healthy natural collagen or otherwise?

    • drjohn says:

      Matrixyl 3000 is a combination of two peptides in palmitoyl (lipid conjugated) form. Th primary one is GHK (or pal-GHK when attached to the lipid). The same peptide linked to a copper molecule is call Cu-GHK or copper peptide. GHK has been widely researched over several decades. Much is known about it’s biochemistry. It is both safe and effective, for wrinkles the clinical studies suggest about 30% efficacy. It modules multiple cellular pathways in skin rejuvenation. It is anti-inflammatory. For a complete up to date review of the research, read this summary. We include Matrixyl in our AnteAge product as it has good synergy with stem cell biology, particularly involving integrins. As with most collagen stimulating substances, the type of collagen created will depend largely on the surrounding milieu – if inflammation is present the collagen tends to become poorly cross linked. If inflammation is tamed, then good basketweave collagen and elastin can result. All collagen you make on your own is natural.

  23. Abby says:

    What do you think about the Osmosis ‘Rescue’ which has Trioxolane as an active ingredient? The company claims that this product “neutralize toxins, calm inflammation, activate epidermal wound repair” is this claim true?

    • drjohn says:

      Oh boy, where do we start. How about with this quote: “Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria. So, trioxanes are cytotoxic (cell killers) and embryotoxic (kills growing babies). They are the basis of molecules used to treat malaria, a parasitic disease. In chemistry, 1,3,5-trioxane is used as a stable, easily handled source of anhydrous formaldehyde – it decomposes to generate three molecules of formaldehyde. Formaldehyde has its own toxic problems.

      From the advertising: “Trioxolane, a specialized extract of sweet wormwood…”. Wormwood has been known since biblical times. It’s use may be associated with miscarriages. This is from the same company that hawks “harmonized H20 – frequency enhanced water for health” which every expert I can find says is fanciful thinking or pure quackery.

      We leave you with what the Bible (New International Version) says on the matter: “The name of the star is Wormwood. A third of the waters turned bitter, and many people died from the waters that had become bitter.” (Revelation 8:11).

  24. Kelly Patterson says:

    Thanks for all your help!
    I started using Anteage duo and want to stay inflammation free with my other products too. I am using Elta MD tinted UV Clear SPF 46 for my sunscreen. Is this a good product for my normal 52 yo skin?

    Active: 9.0% Zinc Oxide, 7.5% Octinoxate. Inactive: Purified Water, Cyclopentasiloxane, Niacinamide, Octyldodecyl Neopentanoate, Butylene Glycol, Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer, Polyisobutene, PEG-7 Trimethylolpropane Coconut Ether, Sodium Hyaluronate, Tocopheryl Acetate, Lactic Acid, Oleth-3 Phosphate, Phenoxyethanol, Iodopropynyl Butylcarbamate, Isopropyl Palmitate, Octyl Stearate, Iron Oxides, Triethoxycaprylylsilane.

  25. I have been using Babor Reversive cream for over two years. It has Toprenone,Agicyl, epocyl, lumicol. They do not offer information on any studies. Can you tell me anything g about their products?

  26. Jane says:

    Although I’m a bit late to it, thank you for this post. I’m disappointed to find that a product I use includes Renovage, more disappointed that companies are willing to use ingredients that are not reliably shown to be effective or safe. It makes me wonder what other skincare ingredients may be giving short term satisfaction but causing potential harm in the long-run…

    I tried to find other critical discussions of this ingredient online, but couldn’t. This ingredient is found in numerous products – I hope this discussion makes its way to product formulators.

    • drjohn says:

      Jane, if you are feeling nerdy you can do a Pubmed search on the latest science. Even if not too nerdy just count the number of peer-reviewed papers linking heat shock proteins with inflammation, inflammatory disorders, heart disease, atherosclerosis, alzheimer’s, neurodegeneration, etc. There may be a positive role for small (hormetic) stress responses, but daily application mimics chronic pathology. Not smart!

  27. Jess says:

    I am interested in purchasing an eye cream from YBF. I notice they also sell another eye product that contains Renovage. My question is should I even consider purchasing from a company that uses Renovage as an ingredient in their product line. I’m aware of some negative results from using this ingredient. I’m confused. A brand that promotes this item must just be selling a fantasy. What do you think?

  28. DrGeorge says:

    Renovage is a cosmetic ingredient consisting of triglyceride, and teprenone, the latter of which is a chemical called geranylgeranylacetone. Teprenone is a pharmaceutical prescribed for the treatment of ulcers and gastritis, among other indications. It has also been studied for possible benefit in preventing colon and ovarian cancers.

    Teprenone is a heat shock protein inducer. When the body’s cells endure stress, particular proteins are released to help protect these cells. In the body, geranylgeranylacetone stimulates the creation of these proteins, thus giving cells resilience and protection from inflammation, free radicals, and other damage to DNA. This may be the mechanisms whereby this chemical has its anti-tumor effects, which are discussed within the article URLs below.

    There is no medical or scientific evidence that suggests that teprenone repairs, protects, or has any benefit directly on skin. There have been no peer-reviewed studies on the subject, and no clinical trials to back up the claim. The only studies that have been done are those that the parties who filed a patent for the use of this chemical for its purported antiaging effect on skin.

    A patent application was filed in 2013 (US20090214607A1) and assigned to Sederma SA, that claimed teprenone had anti-aging benefit when applied to the skin. We are unaware of published medical or scientific evidence that teprenone repairs, protects or has any benefit directly on skin. The inventors who applied for the patent claim they have proof of efficacy, but nothing is readily discoverable that independent, non-biased studies have confirmed these finding.

    Our PubMed search did return a study that claimed teprenone had protective effect against radiation-induced delayed effect on human keratinocytes. Does this translates into real-time, real-world anti-aging skin effects? No conclusion was made. Color us very skeptical.

    A prior answer from DrJohn on BFT about heat shock proteins from September 2018 is germane: “There are a number of peer-reviewed papers linking heat shock proteins with inflammation, inflammatory disorders, heart disease, atherosclerosis, alzheimer’s, neurodegeneration, etc. There may be a positive role for small (hormetic) stress responses, but daily application mimics chronic pathology. Not smart!”

    https://pubmed.ncbi.nlm.nih.gov/23289389/
    http://www.ncbi.nlm.nih.gov/pubmed/19337914
    http://www.ncbi.nlm.nih.gov/pubmed/20724917
    http://www.ncbi.nlm.nih.gov/pubmed/17343825

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