Wetenschappelijk onderzoek over levensverlening

1. Latest advances in antiaging medicine
   Rapid progress is being made in our ability to modify the aging process. Rather than serving as a period of debility and decreasing health, for many people, the later years of life are becoming a period of continued productivity, independence and good health. Progress is also being made in increasing average lifespan. The leading causes of death (cardiovascular disease, cancer, lung disease, diabetes) are the end result of decades-long processes. With current knowledge, it is possible to delay the onset of these diseases. This can be assisted by lifestyle choices incorporating healthful diet, exercise, stress management, and nutritional supplementation. Emerging genomics technology will allow individuals to establish personalized programs, while early detection of heart disease and cancer will contribute to longevity. Biotechnological therapies involving stem cells, recombinant DNA, proteomics, therapeutic cloning and gene-based therapies are expected to play major roles in promoting successful aging. We are at the threshold of artificial intelligence (AI) and nanotechnology (NT). AI will allow for a merging of our biological thinking with advanced forms of non-biological intelligence to vastly expand our ability to think, create and experience. NT will ultimately allow us to build devices able to build molecules much like our current cellular machinery does, one atom at a time. It is the goal of today's antiaging medicine to forestall disease and aging long enough for people to utilize the powerful biotechnology and nanotechnology therapies that will be developed over the decades ahead. These future therapies have the potential to greatly extend longevity.
2. The biology of aging
   In humans, aging is inexorable. The progressive decrease in physiological capacity and the reduced ability to respond to environmental stresses lead to increased susceptibility and vulnerability to disease. Consequently, mortality due to all causes increases exponentially with aging. Attempts at understanding the causes of aging are limited by the complexity of the problem. Aging changes are manifest from the molecular to the organismic level; environmental factors affect experimental observations; secondary effects complicate elucidation of primary mechanisms; and precisely defined, easily measurable biomarkers are lacking. No one unifying theory may exist, since the mechanisms of aging could be quite distinct in different organisms, tissues, and cells. Evolutionary pressures have selected for successful reproduction, making it likely that the post-reproductive physiology of an organism (i.e., aging) is an epigenetic and pleiotropic manifestation of the optimization for early fitness. Indeed, antagonistic pleiotropy, wherein genes that enhance early survival and function but are disadvantageous later in life, may play an overriding role in aging. Theories of aging can be divided into two general categories: stochastic and developmental-genetic. These are not mutually exclusive, particularly when considering the free radical/mitochondrial DNA theory of aging. Increasing evidence suggests that cellular senescence and organismic aging are antagonistically pleiotropic manifestations of evolutionary pressures to prevent malignant transformation. In other words, aging may be the price we pay to avoid cancer. The beneficial paradox may be that the maximum lifespan potential of humans may have been achieved, in part, due to our ability to grow old.
3. A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer
   OBJECTIVE: Although the quest for longevity is as old as civilization itself, only recently have technical and conceptual advances in genomics research brought us to the point of understanding the precise molecular events that make us age. This heralds an era when manipulations of these will enable us to live longer, healthier lives. The present review describes how recent experimental strategies have identified key genes and intracellular pathways that are responsible for ageing and longevity. FINDINGS: In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. The various adverse processes activated upon FOXO suppression include increased generation of reactive oxygen species (ROS). ROS are pivotal for the onset of various common conditions, including hypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer's disease, each of which shortens lifespan. In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases. An understanding of the processes controlled by these FOXOs should permit development of novel classes of agents that will more directly counteract or prevent the damage associated with diverse life-threatening conditions, and so foster a life of good health to a ripe old age. Just like caloric restriction, lifespan can be increased in various species by plant-derived polyphenols, such as resveratrol, via activation of sirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO and other pathways to achieve their beneficial effects on health and lifespan. CONCLUSION: Lifespan is tractable and basic mechanisms are now known. Longevity research complements and overlaps research in most major medical disciplines. Current progress bodes well for an ever-increasing length of healthy life for those who adapt emerging knowledge personally (so-called 'longevitarians').
4. Genetic and Environmental Influences on Exceptional Longevity and the AGE Nomogram
   To live beyond the octogenarian years, population and molecular genetic studies of centenarian sibships indicate that genetic factors play an increasingly important role as the limit of life span is approached. These factors are likely to influence basic mechanisms of aging that in turn broadly influence susceptibility to age-related illnesses. Lacking genetic variations that predispose to disease as well as having variations that confer disease resistance (longevity enabling genes) are probably both important to achieving exceptional old age. The AGE (aging, genetics, environment) nomogram is introduced as an illustrative construct for understanding the influence of environmental and genetic factors on survival to various ages, depending on variations in the hypothesized relative importance of genes and environment to longevity. The rapid rise in the incidence of centenarians could indicate that many more people than we originally thought have the optimal set of genetic factors necessary to get to 100 and beyond. Recent studies indicate the likelihood that such factors will be elucidated in the near future.
5. Replicative Aging, Telomeres, and Oxidative Stress
   Aging is a very complex phenomenon, both in vivo and in vitro. Free radicals and oxidative stress have been suggested for a long time to be involved in or even to be causal for the aging process. Telomeres are special structures at the end of chromosomes. They shorten during each round of replication and this has been characterized as a mitotic counting mechanism. Our experiments show that the rate of telomere shortening in vitro is modulated by oxidative stress as well as by differences in antioxidative defence capacity between cell strains. In vivo we found a strong correlation between short telomeres in blood lymphocytes and the incidence of vascular dementia. These data suggest that parameters that characterise replicative senescence in vitro offer potential for understanding of, and intervention into, the aging process in vivo.
6. Cell Senescence in Human Aging and Disease
   While aging is attributed to "wear and tear," genetic studies show that these effects are avoidable (as is the case in germ cell lines) and occur only when cells down-regulate active (and sufficient) repair mechanisms, permitting degradation to occur. Aging occurs when cells permit accumulative damage by wear and tear, by altering their gene expression rather than vice versa. Using telomerase in laboratory settings, we can currently reset this pattern and its consequences both within cells and between cells. Doing so resets not only cell behavior but the pathological consequences within tissues comprising such cells. We can currently grow histologically young, reconstituted human skin using old human skin cells (keratinocytes and fibroblasts).
7. The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically
   Caloric restriction (CR) and a reduced growth hormone (GH)-insulin-like growth factor (IGF-1) axis are associated with an extension of lifespan across taxa. Evidence is reviewed showing that CR and reduced insulin of GH-IGF-1 axis may exhibit their effects at least partly by their common stimulatory action on autophagy, the cell repair mechanism responsible for the housekeeping of cell membranes and organelles including the free radical generators peroxisomes and mitochondria. It is shown that the life-long weekly administration of an anti-lipolytic drug may decrease glucose and insulin levels and stimulate autophagy and intensify anti-ageing effects of submaximal CR.
8. Approaches to anti-aging intervention: the promises and the uncertainties
   Humans have long sought the elixir to long life. Today, although advances in our understanding of the aging process have given gerontologists new insights in potential anti-aging interventions, public demand for these interventions is outpacing our current knowledge. My presentation begins with a brief historical background that outlines some of the past and present approaches to anti-aging interventions. Using the dietary restriction paradigm as a prototype, discussions center on a three-pathway model that provides the bases to design effective interventions: (1) retardation of biological aging, (2) suppression of age-related disease, and (3) modulation of cross talk between (1) and (2). One other concept useful for discussion in relation to interventions is the enhancement of an organism's resistance to deter vulnerability to aging and disease. These models are best used to explain the efficacy of currently popular interventions such as antioxidant supplementation and hormone therapies. This presentation further highlights the promises that antioxidant supplements hold in warding off oxidative damage as well as their inherent problems and biological limitations. Also discussed here are the promises and uncertainties of anti-aging interventions by genetic manipulation, as seen in animal model studies, and prophylactic treatments targeted against disease, such as hormonal approaches using estrogen and DHEA, as well as other intervening measures.

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Tretenoine

1. Samuel M1, Brooke RC, Hollis S, Griffiths CE. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001782. Interventions for photodamaged skin
   There is conclusive evidence that topical tretinoin improves the appearance of mild to moderate photodamage on the face and forearms, in the short term. However erythema, scaling/dryness, burning/stinging and irritation may be experienced initially. There is limited evidence that tazarotene and isotretinoin benefit patients with moderate photodamage on the face: both are associated with skin irritation and erythema. The effectiveness of other interventions remains uncertain.[Abstract]
2. Grimes P1, Watson J. Cutis. 2013 Jan;91(1):47-54. Treating epidermal melasma with a 4% hydroquinone skin care system plus tretinoin cream 0.025%
   The 4% hydroquinone skin care system plus tretinoin cream 0.025% is effective and well-tolerated in the treatment of melasma.[Abstract]
3. Kircik LH. J Drugs Dermatol. 2012 Sep;11(9):1036-40. Histologic improvement in photodamage after 12 months of treatment with tretinoin emollient cream (0.02%)
   The histologic changes in all subjects could be attributed to a remodeling (elastin) or repair (collagen) process that affected the connective tissue fibers in all layers of the dermis. These results suggest that tretinoin 0.02% may be an effective treatment for photodamage, and additional evaluation is warranted in future studies.[Abstract]
RCT
4. Ho ET1, Trookman NS, Sperber BR, Rizer RL, Spindler R, Sonti S, Gotz V, Mehta R. J Drugs Dermatol. 2012 Jan;11(1):64-9. A randomized, double-blind, controlled comparative trial of the anti-aging properties of non-prescription tri-retinol 1.1% vs. prescription tretinoin 0.025%
   Both test products significantly improved signs of photodamage, including fine and coarse periocular wrinkles, skin firmness, skin tone, mottled pigmentation, tactile roughness, overall photodamage and global photodamage improvement. There were no significant differences in efficacy between the two products for these assessments. The adverse effects (which were graded as mild or less) were those typically seen with topical retinoids. Subjects reported >93 percent overall satisfaction with both products at weeks 8 and 12.[Abstract]
RCT
5. Tucker-Samaras S1, Zedayko T, Cole C, Miller D, Wallo W, Leyden JJ. J Drugs Dermatol. 2009 Oct;8(10):932-6. A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study
   The results showed that, after eight weeks, the retinol moisturizer was significantly more efficacious than the vehicle in improving lines and wrinkles, pigmentation, elasticity, firmness and overall photodamage. Many of these differences were significant at week 4, with a progressive improvement to week 8. This study demonstrates that a formulation containing stabilized retinol is safe and effective to ameliorate the appearance of photoaged skin.[Abstract]
6. Griffiths CE1, Goldfarb MT, Finkel LJ, Roulia V, Bonawitz M, Hamilton TA, Ellis CN, Voorhees JJ. J Am Acad Dermatol. 1994 Jan;30(1):76-84. Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients: a vehicle-controlled trial
   By clinical, colorimetric, and histologic evaluation, 0.1% tretinoin cream significantly lightens the hyperpigmentation of photoaging in Chinese and Japanese patients.[Abstract]
7. Ellis CN1, Weiss JS, Hamilton TA, Headington JT, Zelickson AS, Voorhees JJ. J Am Acad Dermatol. 1990 Oct;23(4 Pt 1):629-37. Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin
   Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded.[Abstract]
CLINICAL
8. Woodley DT1, Zelickson AS, Briggaman RA, Hamilton TA, Weiss JS, Ellis CN, Voorhees JJ. JAMA. 1990 Jun 13;263(22):3057-9. Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils. A preliminary report
   After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites (1.34 anchoring fibrils per micron of lamina densa vs 0.65, respectively). The possible mechanisms by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibiting collagenase, a dermal enzyme that degrades anchoring fibril collagen. We speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.[Abstract]
9. Marks R1, Lever L. Br J Dermatol. 1990 Apr;122 Suppl 35:93-5. Studies on the effects of topical retinoic acid on photoageing
   Tretinoin has been previously shown in animal and clinical studies to stimulate epidermal cell production and to be effective in the treatment of solar keratoses. A double-blind, placebo-controlled study confirmed that topical tretinoin produced an overall improvement in photoaged skin and decreased solar keratoses. There is no evidence that tretinoin has an irritative effect, nor is there any evidence that the improvement in appearance is due to oedema.[Abstract]
10. Weiss JS1, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ JAMA. 1988 Jan 22-29;259(4):527-32. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study
    Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin.[Abstract]
11. Kim H1, Kim N, Jung S, Mun J, Kim J, Kim B, Lee J, Ryoo H, Jung H. Br J Dermatol. 2010 Mar;162(3):497-502. doi: 10.1111/j.1365-2133.2009.09483.x. Improvement in skin wrinkles from the use of photostable retinyl retinoate: a randomized controlled trial
    Retinyl retinoate applied twice daily was significantly more effective than a placebo or retinol in treating periorbital wrinkles. Importantly, no severe side-effects were observed.[Abstract]
RCT
12. Griffiths CE1, Kang S, Ellis CN, Kim KJ, Finkel LJ, Ortiz-Ferrer LC, White GM, Hamilton TA, Voorhees JJ. Arch Dermatol. 1995 Sep;131(9):1037-44. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams
    Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.[Abstract]
RCT
13. Andreano JM1, Bergfeld WF, Medendorp SV. Cleve Clin J Med. 1993 Jan-Feb;60(1):49-55. Tretinoin emollient cream 0.01% for the treatment of photoaged skin
    On forearms, dermatitis was the most common adverse event. Tretinoin 0.01% was generally well tolerated, and skin irritation was minimal. Tretinoin emollient cream 0.01% is a potentially safe, effective treatment for photodamaged skin.[Abstract]
REVIEW
14. Mukherjee S1, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Clin Interv Aging. 2006;1(4):327-48. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety
    Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. .[Abstract]
REVIEW
15. Chung JH1, Eun HC. J Dermatol. 2007 Sep;34(9):593-600. Angiogenesis in skin aging and photoaging
    Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process.[Abstract]
16. Singh M1, Griffiths CE. Dermatol Ther. 2006 Sep-Oct;19(5):297-305. The use of retinoids in the treatment of photoaging
    Although a number of surgical procedures can improve the clinical appearance of photoaged skin, the only medical therapy with proved benefit derived from randomized clinical trial evidence is the use of topical retinoids, particularly tretinoin, isotretinoin, and tazarotene. Retinoids are capable not only of repairing photoaged skin at both the clinical and biochemical levels but their use may prevent photoaging. There is in addition emerging evidence that topical retinoids could be beneficial in the treatment of intrinsically aged skin.[Abstract]
REVIEW
17. Stratigos AJ1, Katsambas AD. Drugs. 2005;65(8):1061-72. The role of topical retinoids in the treatment of photoaging
    Overwhelming clinical and histological evidence indicate that certain structural changes induced by excessive sun exposure can be reversed, to some extent, by the use of topical retinoids. A number of retinoid compounds, for example tretinoin, isotretinoin, retinaldehyde and tazarotene, have been employed for the treatment of photoaged skin, and demonstrate beneficial clinical and histological effects. Adverse effects have been limited to an irritant reaction of variable intensity presenting with dryness, scaling and erythema.[Abstract]
REVIEW
18. Griffiths CE. Clin Exp Dermatol. 2001 Oct;26(7):613-8. The role of retinoids in the prevention and repair of aged and photoaged skin
    Emerging evidence indicates that intrinsic, chronological ageing of the skin shares several mechanistic features with photoageing. Indeed aged skin is characterized by retinoid sensitivity and is probably reparable by application of topical retinoids..[Abstract]
REVIEW
19. Kang S. Dermatol Clin. 1998 Apr;16(2):357-64. Photoaging and tretinoin
    Premature skin aging caused by repeated exposure to solar radiation is called photoaging. Although once considered an irreversible process, it is now established that photoaging can be treated by topical tretinoin. Both from carefully designed controlled clinical studies; and basic investigations into the mechanism by which tretinoin improves photoaged skin, our understanding of photoaging has been enhanced. This article highlights some of these studies which have contributed to our knowledge.[Abstract]
REVIEW
20. Kang S1, Fisher GJ, Voorhees JJ. Arch Dermatol. 1997 Oct;133(10):1280-4. Photoaging and topical tretinoin: therapy, pathogenesis, and prevention
    Repeated exposure to UV radiation from the sun causes premature skin aging. This photoaging is characterized by wrinkles, mottled pigmentations, dry and rough skin, and loss of skin tone. Since the clinical demonstration that the use of topical tretinoin can improve photoaged skin, a great deal of knowledge that may explain wrinkle effacement has been acquired.[Abstract]
REVIEW
21. Helander SD. Drugs Aging. 1996 Jan;8(1):12-6. Treatment of photoaged skin. Efficacy, tolerability and costs of available agents
    Many well constructed trials confirm the clinical efficacy of topical tretinoin for improving fine wrinkling and mild to moderate hyperpigmentation; coarse wrinkling and severe hyperpigmentation respond less well. Histological improvement is well documented, but the precise relationship to clinical response is not clearly established.[Abstract]
REVIEW
22. Leyden JJ. Br J Dermatol. 1990 Apr;122 Suppl 35:83-6. Tretinoin therapy in photoageing: historical perspective
    Tretinoin was shown in the late 1960s to be useful for the treatment of disorders associated with abnormal epithelial differentiation; however, because of irritation, retinoids were only slowly accepted. In the 1970s, evidence accumulated to show that topical tretinoin could modulate many of the abnormalities in the epidermis and dermis associated with photoageing. It has been shown in hairless mice that tretinoin can reverse dermal elastosis with the formation of new collagen and this has led to clinical trials being carried out in man. Randomized, controlled trials have shown that topical tretinoin is effective in the treatment of photoaged skin.[Abstract]
REVIEW
23. Goldfarb MT1, Ellis CN, Weiss JS, Voorhees JJ J Am Acad Dermatol. 1989 Sep;21(3 Pt 2):645-50. Topical tretinoin therapy: its use in photoaged skin
    Therapy is most successful when a liberal amount of tretinoin 0.1% cream is applied to the skin daily. Tretinoin cream has an excellent safety record; a local cutaneous hypervitaminosis A reaction is the only common problem.[Abstract]
24. From Wikipedia, the free encyclopedia Retinoic acid
    Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development.[Article]
25. 
    .[Abstract]

Glycolzuur

1. Kaminaka C1, Uede M, Matsunaka H, Furukawa F, Yamomoto Y. Dermatol Surg. 2014 Mar;40(3):314-22. doi: 10.1111/dsu.12417. Clinical evaluation of glycolic acid chemical peeling in patients with acne vulgaris: a randomized, double-blind, placebo-controlled, split-face comparative study
   Forty percent GA peels significantly improved moderate acne in this study. It is effective and safe in Asians.[Abstract]
2. Pain S1, Altobelli C, Boher A, Cittadini L, Favre-Mercuret M, Gaillard C, Sohm B, Vogelgesang B, André-Frei V. Int J Cosmet Sci. 2011 Dec;33(6):535-42. doi: 10.1111/j.1468-2494.2011.00667.x. Surface rejuvenating effect of Achillea millefolium extract
   A. millefolium extract at 2% significantly improved the appearance of wrinkles and pores compared with placebo. Results were also directionally better than those of glycolic acid that was chosen as reference resurfacing molecule.[Abstract]
3. Bertin C1, Zunino H, Lanctin M, Stamatas GN, Camel E, Robert C, Issachar N. Int J Cosmet Sci. 2008 Jun;30(3):175-82. doi: 10.1111/j.1468-2494.2008.00441.x. Combined retinol-lactose-glycolic acid effects on photoaged skin: a double-blind placebo-controlled study
   In conclusion, our results demonstrate that topical application of a combination of retinol, lactose and glycolic acid has significantly improved the appearance of photodamaged skin.[Abstract]
4. Kaidbey K1, Sutherland B, Bennett P, Wamer WG, Barton C, Dennis D, Kornhauser A. Photodermatol Photoimmunol Photomed. 2003 Feb;19(1):21-7. Topical glycolic acid enhances photodamage by ultraviolet light
   Short-term application of 10% glycolic acid sensitizes the skin to the damaging effects of UV light. This photosensitivity is reversed within a week of terminating treatments.[Abstract]
5. Alam M1, Omura NE, Dover JS, Arndt KA. Dermatol Surg. 2002 Jun;28(6):475-9. Glycolic acid peels compared to microdermabrasion: a right-left controlled trial of efficacy and patient satisfaction
   In this study, patients appeared to prefer low-strength glycolic acid peels to low-intensity microdermabrasion for facial rejuvenation. Differences in patient satisfaction were subtle and may be technique dependent.[Abstract]
6. Pi rard GE1, Kligman AM, Stoudemayer T, Lévêque JL. Dermatology. 1999;199(1):50-3. Comparative effects of retinoic acid, glycolic acid and a lipophilic derivative of salicylic acid on photodamaged epidermis
   In the presently tested concentrations and formulations, RA had a beneficial impact upon the aging epidermis. LSA mimicked RA but with somewhat lesser efficacy. By contrast, GA appeared almost inactive.[Abstract]
7. Appa Y. Skin Pharmacol Appl Skin Physiol. 1999 May-Jun;12(3):111-9. Retinoid therapy: compatible skin care
   The results of a double-blind clinical study demonstrate that daytime usage of one of two 8% glycolic acid lotions in addition to nightly applications of Renova was well tolerated as part of a comprehensive skin care and sun protection program.[Abstract]
8. Thibault PK1, Wlodarczyk J, Wenck A. Dermatol Surg. 1998 May;24(5):573-7; discussion 577-8. A double-blind randomized clinical trial on the effectiveness of a daily glycolic acid 5% formulation in the treatment of photoaging
   Unneutralized 5% glycolic acid topical cream when used on a regular daily basis can improve some photoaging effects.[Abstract]
9. Stiller MJ1, Bartolone J, Stern R, Smith S, Kollias N, Gillies R, Drake LA. Arch Dermatol. 1996 Jun;132(6):631-6. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial
   Topical 8% glycolic acid and 8% L-lactic acid creams are modestly useful in ameliorating some of the signs of chronic cutaneous photodamage. These agents are well tolerated and available without prescription.[Abstract]
OTHER
10. Perricone NV1, DiNardo JC. Dermatol Surg. 1996 May;22(5):435-7. Photoprotective and antiinflammatory effects of topical glycolic acid
    The studies demonstrated that topical glycolic acid provides a photoprotective effect to pretreated skin yielding an SPF of approximately 2.4. In addition, when glycolic acid is applied to irradiated skin, it accelerates resolution of erythema. The data obtained from both studies support the hypothesis that glycolic acids acts as an antioxidant.[Abstract]
11. 
    .[Abstract]

Salicylzuur

1. Oresajo C1, Yatskayer M, Hansenne I. J Cosmet Dermatol. 2008 Dec;7(4):259-62. doi: 10.1111/j.1473-2165.2008.00403.x. Clinical tolerance and efficacy of capryloyl salicylic acid peel compared to a glycolic acid peel in subjects with fine lines/wrinkles and hyperpigmented skin
   Five percent to 10% of LHA peel is generally safe and as effective as 20-50% GA peel in reducing facial hyperpigmentation and fine lines/wrinkles.[Abstract]
2. Dahl A1, Yatskayer M, Raab S, Oresajo C. J Drugs Dermatol. 2013 Jan;12(1):52-8. Tolerance and efficacy of a product containing ellagic and salicylic acids in reducing hyperpigmentation and dark spots in comparison with 4% hydroquinone
   This study suggests that this new product provided comparable skin depigmentation benefit to the benchmark product. In addition, the product appears to have better esthetics (texture, pleasantness to use, skin feel) than the 4% HQ product.[Abstract]
3. Babayeva L1, Akarsu S, Fetil E, Güne? AT. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):328-33. doi: 10.1111/j.1468-3083.2010.03793.x. Comparison of tretinoin 0.05% cream and 3% alcohol-based salicylic acid preparation in the treatment of acne vulgaris
   Combination of SA+CDP and all-TRA+CDP was effective in decreasing lesion counts and well tolerated with minimal local cutaneous reactions in patients with mild to moderate AV.[Abstract]
4. Piérard GE1, Nikkels-Tassoudji N, Arrese JE, Piérard-Franchimont C, Lévêque JL. Dermatology. 1997;194(4):398-401. Dermo-epidermal stimulation elicited by a beta-lipohydroxyacid: a comparison with salicylic acid and all-trans-retinoic acid
   Both beta-lipohydroxyacid and tretinoin induced enhanced epidermal proliferation and thickness with activation of factor XIIIa+dendrocytes. The effects were more pronounced at the tretinoin-treated site. We speculate that TNF-alpha might mediate some of the dermal effects. The beta-lipohydroxyacid mimics some of the stimulatory effects of tretinoin on the epidermis and dermis. This new compound should be listed among topical products boosting the skin tissues affected by ageing.[Abstract]
5. Abdel-Daim M1, Funasaka Y, Kamo T, Ooe M, Matsunaka H, Yanagita E, Itoh T, Nishigori C. J Dermatol. 2010 Oct;37(10):864-72. doi: 10.1111/j.1346-8138.2010.00859.x. Effect of chemical peeling on photocarcinogenesis
   hese results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells.[Abstract]
6. Gladstone HB1, Nguyen SL, Williams R, Ottomeyer T, Wortzman M, Jeffers M, Moy RL. Dermatol Surg. 2000 Apr;26(4):333-7. fficacy of hydroquinone cream (USP 4%) used alone or in combination with salicylic acid peels in improving photodamage on the neck and upper chest
   Hydroquinone 4% cream with 2% glycolic acid is safe and effective in improving photodamage on the neck and upper chest when used alone or in combination with salicylic acid peels.[Abstract]
7. Fabbrocini G1, De Padova MP, Tosti A. Facial Plast Surg. 2009 Dec;25(5):329-36. doi: 10.1055/s-0029-1243082. Chemical peels: what's new and what isn't new but still works well
   Various chemicals have been used as peeling agents, of which the most used are the alpha-hydroxy acids, such as glycolic acid, or beta-hydroxy acids, such as salicylic acid. The choice of the compound is linked to the different indications and to the depth of the desired peeling. Phenol is still the best agent for deep peeling but requires specific indications, prescription, and post-peeling care.[Abstract]

Vitamine-C

1. Nusgens BV1, Humbert P, Rougier A, Colige AC, Haftek M, Lambert CA, Richard A, Creidi P, Lapière CM. J Invest Dermatol. 2001 Jun;116(6):853-9. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis
   The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vitamin and unrelated to the level of actinic damage. The results indicate that the functional activity of the dermal cells is not maximal in postmenopausal women and can be increased.[Abstract]
2. Darr D1, Combs S, Dunston S, Manning T, Pinnell S. Br J Dermatol. 1992 Sep;127(3):247-53. Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage
   Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.[Abstract]
RCT
3. Traikovich SS. Arch Otolaryngol Head Neck Surg. 1999 Oct;125(10):1091-8. Use of topical ascorbic acid and its effects on photodamaged skin topography
   A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.[Article]
RCT
4. Humbert PG1, Haftek M, Creidi P, Lapière C, Nusgens B, Richard A, Schmitt D, Rougier A, Zahouani H. Exp Dermatol. 2003 Jun;12(3):237-44. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo
   Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.[Abstract]
RCT
5. Greul AK1, Grundmann JU, Heinrich F, Pfitzner I, Bernhardt J, Ambach A, Biesalski HK, Gollnick H. Skin Pharmacol Appl Skin Physiol. 2002 Sep-Oct;15(5):307-15. Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins E and C, carotenoids, selenium and proanthocyanidins
   From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.[Abstract]
6. 
   .[Abstract]
7. 
   .[Abstract]
8. 
   .[Abstract]

Alpha hydroxyacids

1. Julia A. Kneedler, Sharon S. Sky, and Linda R. Sexton firstskinfoundation.org/
   The skin-rejuvenating properties of certain alpha-hydroxy acids have been known for centuries. Cleopatra allegedly bathed in spoiled milk, which contains lactic acid, and the women of the French court washed their faces in spoiled wine, which contains tartaric acid. Today, alpha-hydroxy acids (AHAs) are widely used in skin care products. They are the most popular ingredient to enter that marketplace in recent years. In 1996, researchers Perricone and DiNardo reported that approximately forty-five companies were manufacturing over two hundred AHA-containing products, ranging from over-the-counter moisturizers and cosmetics to chemical peels administered by physicians.[Article]
RCT
2. Berardesca E1, Distante F, Vignoli GP, Oresajo C, Green B. Br J Dermatol. 1997 Dec;137(6):934-8. Alpha hydroxyacids modulate stratum corneum barrier function
   Alpha hydroxyacids (AHAs) are used to enhance stratum corneum desquamation and improve skin appearance. The purpose of this study was to evaluate whether some AHAs improve skin barrier function and prevent skin irritation. This study shows that AHAs can modulate stratum corneum barrier function and prevent skin irritation; the effect is not equal for all AHAs, being more marked for the molecules characterized by antioxidant properties.[Abstract]
CLINICAL
3. Edison BL1, Green BA, Wildnauer RH, Sigler ML. Cutis. 2004 Feb;73(2 Suppl):14-7. A polyhydroxy acid skin care regimen provides antiaging effects comparable to an alpha-hydroxyacid regimen
   Stinging and burning were significantly worse for subjects in the AHA treatment group at both week 6 and 12, and degree of sensitivity was rated worse for the AHA regimen as well. The present study shows the enhanced mildness of PHAs and their equivalence in providing antiaging benefits compared with an AHA regimen.[Abstract]
CLINICAL
4. Schreml S1, Meier RJ, Albert MG, Seidl U, Zeller V, Behm B, Landthaler M, Abels C, Babilas P. Skin Pharmacol Physiol. 2012;25(1):34-8. doi: 10.1159/000331204. The impact of 10% ?-hydroxy acid emulsion on skin pH
   After a 10-min application time, the 10% AHA O/W emulsion reduces the pH(ss) (for at least 3 h) and pH(sc) in deep layers of the SC.[Abstract]
RCT
5. Ditre CM1, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, Van Scott EJ. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):187-95. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study
   Treatment with AHAs produced significant reversal of epidermal and dermal markers of photoaging.[Abstract]
REVIEW
6. Green BA1, Yu RJ, Van Scott EJ. Clin Dermatol. 2009 Sep-Oct;27(5):495-501. doi: 10.1016/j.clindermatol.2009.06.023. Clinical and cosmeceutical uses of hydroxyacids
   The most commonly used hydroxyacid is glycolic acid, an alpha-hydroxyacid that has been used extensively in cosmetic antiaging formulations, moisturizers, and peels, and in treatment products to improve hyperpigmentation and acne. The newer polyhydroxy and bionic acids offer the benefits of alpha-hydroxyacids without irritation, making them suitable for use on sensitive skin, rosacea, and after cosmetic procedures.[Abstract]
7. 
   .[Abstract]

Peptides

1. Lupo MP1, Cole AL. Dermatol Ther. 2007 Sep-Oct;20(5):343-9. Cosmeceutical peptides
   Peptide cosmeceuticals are one of the new, popular options to treat aging skin. There are three main categories of cosmeceutical peptides: signal peptides, neurotransmitter-affecting peptides and carrier peptides. Although their benefits currently may not be as rigorously tested as most FDA-regulated drugs, the evidence to support their use is growing. This article attempts to review the various current popular cosmeceutical peptides, the published studies on their theoretical effects, and their practical use in dermatology.[Abstract]
2. Grosicki M, Latacz G, Szopa A, Cukier A, Kie?-Kononowicz K. Acta Biochim Pol. 2014;61(1):29-32. The study of cellular cytotoxicity of argireline - an anti-aging peptide
   Argireline is well know, innovative anti-aging product used in the cosmetic market. This short chain peptide is used as active ingredient in dermal ointment and creams. Argireline prevents formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction. Argireline does not require under skin muscle injections and it is believed to be relatively safe. However, despite the fact that some toxicity data has been provided by the product manufacturer, there is an evident lack of reliable information about cytotoxicity of argireline in the literature. However, the significant cytotoxicity of argireline solution was observed under 18 to 10 000 fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin.[Article]
3. Kasuyama K1, Tomofuji T, Ekuni D, Azuma T, Irie K, Endo Y, Morita M. J Periodontal Res. 2012 Apr;47(2):159-64. doi: 10.1111/j.1600-0765.2011.01414.x. Effects of topical application of inorganic polyphosphate on tissue remodeling in rat inflamed gingiva
   Topical application of poly(P) may induce connective tissue remodeling, contributing to improvement of inflamed gingiva in rats.[Abstract]

Argireline

1. Wang Y1, Wang M, Xiao XS, Huo J, Zhang WD. J Cosmet Laser Ther. 2013 Aug;15(4):237-41. doi: 10.3109/14764172.2013.769273. The anti-wrinkle efficacy of Argireline
   This study revealed that Argireline could improve the histological structure of skin tissue and rejuvenate the aging skin.[Abstract]
2. Wang Y1, Wang M, Xiao S, Pan P, Li P, Huo J. Am J Clin Dermatol. 2013 Apr;14(2):147-53. doi: 10.1007/s40257-013-0009-9. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study
   This study showed that argireline had a significant anti-wrinkle effect in Chinese subjects.[Abstract]
3. Ruiz MA1, Clares B, Morales ME, Cazalla S, Gallardo V. J Cosmet Sci. 2007 Mar-Apr;58(2):157-71. Preparation and stability of cosmetic formulations with an anti-aging peptide
   This article reviews the physiological basis and mechanism of action of the active cosmetic ingredient acetyl hexapeptide-8 (Argireline). We prepared two formulations: an emulsion with an external aqueous phase for normal to dry skin, and a gel for oily skin. Laboratory analyses, rheology tests and in vitro release assays were used to evaluate the stability of these formulations for cosmetic treatment.[Abstract]

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