Melatonin: sleep aid, antioxidant, anti-aging drug & more

Changes in the amount of reduced glutathione and activity of antioxidant enzymes in chosen mouse organs influenced by zymosan and melatonin administration

Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT)  and glutathione peroxidase (GSHPx) are vital components of the  antioxidative barrier in animal cells. It is suggested more often now  that the effectiveness of the protection of cells against the oxidative stress caused by the inflammation process depends on the  amount of GSH and the activity of SOD, CAT and GSHPx. That is why the  effect of zymosan A (40 mg/kg body mass) and the combined treatment  with zymosan A (at the same dose) and melatonin (50 mg/kg body mass)  on the amount of GSH in the blood and the amount of GSH and activity  of SOD, CAT and GSHPx in the brain, liver and kidneys of male mice was  estimated. Animals (n = 108) were decapitated after 3, 6 and 24 hours  since the moment of the administration of only zymosan A, and combined  zymosan A and after one hour melatonin. After the injection of zymosan  A it was found that the amount of GSH is significantly lower after 3  and 6 hours in the blood and studied organs. The administration of  zymosan A, followed by the administration of melatonin limited the  decrease in the amount of this tripeptide in the same time.  Simultaneously, the decrease in the amount of GSH in the studied  organs was accompanied by a similar decrease in the activity of SOD,
CAT and GSHPx after the injection of only zymosan A and a limited  decrease in the activity after the administration of both zymosan A  and melatonin. It is suggested that a decreased content of GSH and a  decrease in the activity of the studied antioxidative enzymes is  caused by the oxidative stress accompanying the inflammation process.
PMID:21555265

J Neurochem. 2006 Jul;98(1):267-78.

Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementation

Bertrand PP, Bertrand RL, Camello PJ, Pozo MJ. Department of
Physiology, School of Medical Sciences, University of New South Wales,
Sydney, NSW, Australia. dr.p.bertr…@gmail.com

Ageing is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted.  Enterochromaffin (EC) cells containing serotonin (5-HT) and melatonin  may play a major role in maintaining gut function during ageing. Our  aim was to characterise the mucosal availability of 5-HT and melatonin  in the ileum and colon of a mouse model of ageing. Female young mice  (2-5 month; n = 6), aged mice (22-24 months; n = 6) and aged mice  treated with melatonin (n = 6; 10 mg/kg/day) were examined.
Electrochemical methods were used to measure 5-HT and melatonin  concentrations near the mucosal surface of ileum and distal colon.  Amperometry studies showed that steady state levels of 5-HT from ileum
and colon were decreased in aged mice treated with melatonin when  compared to aged mice, while compression-evoked 5-HT release was  unchanged. Differential pulse voltammetry studies showed that young
mice had concentrations of 5-HT of 4.8 +/- 0.8 mum in the ileum and  4.9 +/- 1.0 mum in the colon. Concentrations of melatonin were 5.7 +/-  1.4 mum in the ileum and 5.6 +/- 1.9 mum in the colon. Compared to
young mice, the levels of 5-HT and melatonin were increased in aged  mice (combined ileum and colon: 5-HT = 130% and melatonin = 126% of  young mice) and decreased in melatonin-treated mice (5-HT = 94% and
melatonin = 82%). In conclusion, our data show that the availability  of gut 5-HT and melatonin is increased in aged mice and melatonin  treatment suppresses natural gastrointestinal production of 5-HT and
melatonin in the aged mouse intestine. PMID:20374441

Melatonin seems to exert its antioxidant effect in GIS tract by
stimulating SOD and GSH-Px. Selenium also seems to have an antioxidant
contribution on protecting rat gastrointestinal tract I-R injury.
http://www.ncbi.nlm.nih.gov/pubmed/11093033

The higher plasma levels of melatonin in DSS-treated mice might be due
to a stress-induced increase in the production of gastrointestinal
(GIT) melatonin. http://www.ncbi.nlm.nih.gov/pubmed/8609593

Experiments were performed to determine whether diurnal variations in
apoptosis in the mouse small intestine after irradiation with 2.5 Gy
gamma rays depended on the time of day that the mice were irradiated.
http://www.ncbi.nlm.nih.gov/pubmed/9525500

Eksp Klin Farmakol. 2010 Jan;73(1):7-9.

Comparative experimental study of the psychotropic and chronotropic
activity of adaptogenic phytopreparations and melaxen.

Arushanian EB, Naumov SS.

Adaptogenic drugs of plant origin (complex phytopreparation tonizid,
Ginkgo biloba extract bilobil) and hormonal origin (melaxen or
melatonin) exhibit similar spectra ofpsychotropic activity in rats,
which are manifested by improved memory, increased locomotion and
investigation activity, and decreased anxiety. At the same time, these
drugs had different chronotropic properties, depending on the schedule
(acute vs. repeated) and daytime (morning vs. evening) of
administration. PMID:20184280

Eksp Klin Farmakol. 2009 Jul-Aug;72(4):3-5.

Dependence of atropin-induced amnesia fluctuations on the state of
pineal gland.

Arushanian EB, Beĭer EV, skorniakoc AA.

Atropin produces weakening of the memory on the model of passive
avoidance reaction in rats, the effect being more pronounced in
evening hours. The drug effect is increased in pinealectomized animals
and attenuated by the pineal hormone melatonin, also differently in
daytime. PMID:19803360

Eksp Klin Farmakol. 2006 Nov-Dec;69(6):17-9.

Effects of melatonin and motherwort tincture on the emotional state
and visual functions in anxious subjects.

Ovanesov KB, Ovanesova IM, Arushanian EB.

The chronic administration of melatonin (0.75 mg at night, 10 days)
led to a significant decrease in the thresholds of retinal brightness
sensitivity and improved the emotional state in anxious young
subjects. Analogous changes were less pronounced after the treatment
with common motherwort (Leonurus cardiaca) tincture. It is suggested
that there is a relation between the limitation of anxiety and the
improvement of visual function (sensitivity). PMID:17209457

Eksp Klin Farmakol. 2006 Nov-Dec;69(6):13-6.

Comparative study of the effects of melatonin and epitalon on the
protracted memory under the shuttle labyrinth test conditions in rats
in the course of aging.

Vinogradova IA.

The influence of the chronic administration of melatonin (epiphyseal
hormone) and epitalon (a synthetic tetrapeptide increasing melatonin
production) on the learning process and the protracted memory has been
studied in LIO rats in the course of aging for 2 years under standard
illumination regime (12L :12D). The daily administration of melatonin
(Sigma, USA) with drinking water (in 10 mg/liter dose at night) in
rats beginning with the age of 4 months did not influence the learning
processes in young and adult animals but it was found to contribute to
optimization of the brain cognitive function in rats in the course of
aging, by improving the protracted memory process. Epitalon
administered in a daily dose of 0.1 microg per animal beginning with
the age of 4 months showed mnemotropic properties (decreasing the
extent of memory disorders) in old rats under conditions of the
shuttle labyrinth test. PMID:17209456

Skin Treatments and Dermatological Procedures to Promote Youthful Skin

Skin Treatments and Dermatological Procedures to Promote Youthful Skin

Paul G Sator

Department of Dermatology, Municipal Hospital Lainz, Vienna, Austria

Abstract

The skin, the largest organ of the body, is the organ in which changes associated with aging are most visible. With increasing frequency, patients are requesting information and treatments that improve the appearance of their skin. Corresponding to this trend, there is an increasing number of products and methods available that claim to aid this pursuit. First, a change of the patient’s lifestyle (eg, sun behavior, nicotine abuse, and nutrition) must take place. Only then may other methods be used. This article reflects on the following topics: topical retinoids, peels, botulinum neurotoxin, soft tissue fillers, lasers, topical and systemic endocrinological therapies, and phytohormones. A thorough knowledge of the properties (benefits, limitations, and complications) of the expanding array of possibilities for rejuvenation of the skin is essential for any physician treating patients with cosmetic complaints.

Keywords: skin aging, topical retinoids, peels, botulinum neurotoxin, soft tissue fillers, lasers, topical endocrinological therapies, systemic endocrinological therapies, phytohormones

Introduction

The skin is one of the largest organs of the body and, like all other tissues, it undergoes degenerative processes during aging. The skin represents the major organ in which aging-related changes are visible (Zouboulis and Boschnakow 2001). Skin aging is associated with increased rates of skin diseases including skin tumors, and with concomitant psychological distress caused by the deterioration in appearance. Although the main focus of public medicine has long been on age-related chronic diseases of other systems, such as arthritis, heart disease, and cancer (Kligman and Koblenzer 1997), skin aging and its diseases have become increasingly important. Most women in developed societies can expect to spend one-third or more of their lifetime in the postmenopausal period (Kligman and Koblenzer 1997) when the external signs of aging are of utmost importance for most.

Skin aging is caused by a combination of factors including genetic disposition and endocrinological background as well as UV light, life habits (nutrition, nicotine, alcohol, and drugs), catabolic (infections and tumors), and further environmental factors. Many women notice a sudden onset of signs and symptoms of skin aging during menopause, such as a rise in skin dryness, loss of firmness, decrease in elasticity, and increase in skin looseness. There is a connection between these clinical signs and such phenomena as decrease in collagen and elastin, changes in basic substance, the ratio of type I/type III collagen, and alterations in vascularization (Brincat 2000). The external signs of skin aging are reflected in the histopathologic findings of the skin (Broniarczyk-Dyla and Joss-Wichman 2001).

Dermatology patients are requesting information and treatments to improve the appearance of their skin with increasing frequency. The number of products and methods claiming to aid in this pursuit are rising. Many different ways may be helpful. Patients look for a prompt improvement while physicians emphasize safety and efficacy.

General procedures

Sun protection

Sun protection is essential for every age and is a necessary addition to all other interventions against skin aging. Chronic low-dose irradiation by the sun causes wrinkles (Kambayashi et al 2001; Gordon 2005). Ultraviolet irradiation reduces production of type I procollagen, the major structural protein in human skin (Quan et al 2004). To avoid photoaging, it is essential to use sunscreens every day and to protect one’s skin against UV A and B rays (a sun protection factor 15 is adequate, but a higher one is better). In addition, it is also important to use protective clothing or hats and to avoid the sun wherever possible.

Skin care

Cleansing and moisturizing the skin is important for many people. Properly cleaned and moisturized skin feels good to most people and looks better than dry skin. Effective products are available from most cosmetic companies and prevent irritant skin reactions and improve barrier functions. Sun protection, avoidance of cigarette smoke, and balanced nutrition is essential for the prevention of skin aging.

Topical retinoids

The topical retinoids, tretinoin and tazarotene, improve mottled hyperpigmentation, fine wrinkles, roughness, and lentigines (Kligman et al 1986; Kang et al 2001; Weiss 2005). One problem is skin irritation. To minimize this problem, it is useful to start with a relatively mild concentration of topical retinoids. If this is not enough, patients should reduce the application frequency. The aim must be to use the highest concentration that can be tolerated without significant irritation of the skin.

Peels

There are three categories of peels: deep peels (eg, phenol peel), medium peels (eg, 30% trichloracetic acid peel), and superficial peels (eg, alpha hydroxyl and salicylic acid peel). Creams with alpha hydroxyl and salicylic acid are also available for the everyday use of the patient. Depending on the depth of the peel, peels remove the uppermost layers of the skin.

Botulinum neurotoxin

Botulinum neurotoxin is a paralysing substance. It is used for softening glabellar frown lines, horizontal forehead lines, crow’s feet, perioral smile lines, platysmal bands of the neck, and to elevate the eyebrows and lateral corners of the mouth (Gordon 2005).

A careful history should be taken to avoid complicating neurologic problems or the ingestion of medications that may interfere with the toxin. The toxin diffuses about 1 cm–1.5 cm from the injection site. This must be considered to avoid eyelid ptosis, for example. The patient should not manipulate the treated area after treatment to avoid unintended diffusion of the toxin. The contraction of the treated muscles after treatment may increase toxin uptake and increase the effectiveness of treatment. The effect of the toxin is seen after about a week.

Soft tissue fillers

Physicians have been searching for the ideal filler for more than a century. The use of injected paraffin for cosmetic purposes more than 100 years ago resulted in paraffinomas (Murray et al 2005). Many substances are available today.

Collagens

Collagen is a fibrous, extracellular, insoluble protein comprising a major component of connective tissues. Injectable collagen consists of varying concentrations of highly purifed bovine or human collagen. Sensitivity reactions and granulomatous responses have occurred in 1%–3% and 0.5% of patients, respectively (Cooperman et al 1985). Minor side effects such as bruising, redness, and swelling are seen after injection, but tend to resolve after a few days. Reimplantation is usually required in 3–6 months.

Bovine collagen

Bovine collagen is available in several formulations for fine lines as well as for deeper lines and folds. Patients must be allergy tested because of the possibility of rare allergic reactions. Two tests must be performed 3 weeks apart and treatment cannot be started until 3–4 weeks after the second allergy test.

Human-based collagen

No allergy testing is required.

Hyaluronic acid

Hyaluronic acid is a component of all connective tissues and is abundant in the human dermis. It is a naturally occurring glycosaminoglycan biopolymer, which provides a fluid matrix or lattice on which collagen and elastic fibers may develop. Its hydrophilic nature attracts and retains water (Pollack 1999). The incidence of allergic reactions is so low that no allergy testing is required. Corrections with hyaluronic acid generally last longer than with collagen.

There are also several formulations for fine to deep lines. There are products that are manufactured through bacterial fermentation and there are others that are extracted from rooster combs. Patients using the latter must not have an allergy to avian products.

Unusual hypersensitivity and granulomatous foreign body reactions have been reported, but hyaluronic acids are generally safe and practical and need no allergy testing (Murray et al 2005).

Autologous fat

Neuber introduced the use of autologous fat for tissue augmentation in 1893 (Neuber 1893). Over the years, the popularity of Neuber’s method has grown, but there is still no evidence-based gold standard method around. The longest lasting results are seen when used for atrophic skin conditions. Adverse events, such as fat necrosis, are temporary but not uncommon.

Allogenic products

Allogenic material is either obtained from cadaveric dermis or fascia, or engineered by methods using human cell lines and has a high biocompatibility with low antigenicity. These products are similar to the bovine collagens in indication and technique, but do not require allergy tests and have a shorter longevity.

Synthetic products

The production of synthetic products is cheaper and they are semipermanent or permanent implants. One of the first synthetic fillers was silicone. Today there are several substances available such as polylactic acid, polyalkylamide, polyacrylamide, and polytetrafluoroethylene. Adverse reactions with these agents can be serious.

Lasers

Laser is the acronym for “light amplification by the stimulated emission of radiation”. Schawlow and Townes developed the first laser in 1958 (DiBernardo and Cacciarelli 2005). Lasers use light at various frequencies to attain a specific clinical result. They can be categorized by the medium in which the light energy is produced. Mechanisms of action include selective thermolysis and specific cell stimulation while leaving normal tissue unaffected. The immune system clears the unwanted material. Lasers can be used to cut, destroy, cauterize, and vaporize tissue. Dermatological indications are skin rejuvenation, tattoo removal, hair removal, and improvement in various skin abnormalities. For example, an ablative laser such as CO₂ or erbium would be considered for skin rejuvenation. Complications could be pigment changes, superficial skin changes, scarring, infection, bleeding, and accidential eye injury.

Surgical procedures

There are many methods of cosmetic surgery such as facelifts not covered by this article. Space limitations preclude an extensive discussion of this field.

Endocrinological therapies for skin aging

Skin is a target organ for various hormones (Zouboulis 2000). Sex steroids have a profound influence on both skin development and composition; adequate levels are required to facilitate its structural integrity and functional capacity (Raine-Fenning et al 2003). Hormonal action requires the binding of the hormone to specific receptors (Zouboulis 2000). Estrogen and other hormone receptors have been detected, inter alia, in keratinocytes, fibroblasts, sebaceous glands, hair follicles, endocrine glands, and blood vessels (Schmidt et al 1990). The receptors vary in density according to site, with higher concentrations of estrogen receptors in facial skin than in the skin at the pelvis or breast. Decreased sex hormones thus induce a reduction of those skin functions that are under hormonal control.

In clinical terms, many females experience a sudden onset of skin aging symptoms several months after menopause. One of the first signs which women experience is increasing skin dryness followed by a loss of skin firmness and elasticity. The increasing looseness of the skin at that stage outweighs other symptoms such as wrinkles. These symptoms correspond to changes in collagenous and elastic fibers that have been reported to be due to estrogen deficiency (Schmidt et al 1994). A significant decrease in skin collagen starting at menopause has previously been demonstrated (Castelo-Branco et al 1992). This negative effect of the menopausal years on the skin was first described by Albright in 1940, who noted that older women with osteoporotic fractures had a higher incidence of altered skin (Albright et al 1940). Among the various types of collagen, types I and III are of major relevance. Type I collagen represents the predominant collagen type in adult human skin whereas type III collagen, also widely distributed throughout the body, predominates in fetal tissues. Both total collagen content and the ratio of type III to type I collagen decline with age (Sawas et al 1993). Skin collagen contents in adults decreases by 1% every year (Shuster et al 1985). This process is more evident in women than in men. Approximately 30% of skin collagen is lost in the first five years after menopause, with an average decline of 2.1% per postmenopausal year over a period of 20 years. Estrogens reverse this trend and increase skin collagen (Zouboulis 2000). Estrogens also enhance the synthesis of hyaluronic acid and promote water retention (Epstein and Munderloh 1975). Animal studies indicate that estrogens induce several changes in the connective tissue of the dermis, including increased mucopolysaccharide incorporation, hydroxy-proline turnover, and alterations in the extracellular matrix (Holland et al 1994).

Epidermal cells – keratinocytes, Langerhans’ cells, and melanocytes – are also target cells of steroid hormones (Zouboulis 2000). The estrogen receptor complex is able to support the expression of growth factors such as insulin-like growth factor type one (IGF-I), a mitosis-enhancing protein for keratinocytes (Tavakkol et al 1999). The Langerhans’ cells are influenced by progesterone, with their number increasing during the luteal phase. Melanocytes are stimulated by 17β-estradiol (Gruber et al 2002).

Sex steroids are involved in many extragenital organ systems such as the urogenital tract, skin and hair, breast, and cardiovascular, nervous, or skeletal systems. Considering that most women spend one-third of their lives with estrogen deficiency, the potential field of action for hormone replacement therapy (HRT) is becoming increasingly larger.

Topical treatment

A placebo-controlled study examined the effect of a topically applied conjugated estrogen skin care cream (Premarin® 0.625 mg/g ointment) in 54 women (Creidi et al 1994). Evaluation criteria were profilometry and measurements of skin thickness by ultrasound. After a 24-week treatment period there was a significant increase in skin thickness in the Premarin® group as compared to the placebo group. Even in regard to small wrinkles, a significant reduction was observed in comparison to the placebo group after 12 and 24 weeks. No side effects were found.

A study was published on the action of topical 0.3% estriol and 0.01% 17β-estradiol in 59 patients (Schmidt et al 1996). The criteria evaluated by the authors were profilometry, corneometry, and clinical signs. Wrinkle depth was significantly reduced and skin hydration was improved. Apart from a rise in prolactin, no other systemic hormonal effects were detected. Histological tests of collagen parameters in 10 patients showed a significant increase in the collagen III fraction at the end of therapy after 24 weeks.

In a recent study, the effects of a 0.01% 17β-estradiol cream were compared with those of a 15% glycolic acid cream and a combination of both (Fuchs et al 2003). The effects examined in 65 patients after 6 months indicated an increase in epidermal thickness and were most marked in the combination group (38%), followed by the glycolic acid group (27%), and the 17β-estradiol group (23%).

Systemic hormone replacement therapy

A HRT consists of two components: estrogens and progestagens. Estrogens administered as monotherapy may result in undesired hyperplasia of the endometrium. To avoid this event, synthetic derivatives of progesterone and testosterone, known as progestagens, are combined with an estrogen compound and may be applied in a cyclical or continuous mode. An estrogen monotherapy is feasible in hysterectomized women, with a choice of oral, transdermal, and vaginal forms of application available.

Beneficial effects of HRT on the skin have been documented by several studies in respect of skin thickness as a mirror image of collagen content (Brincat et al 1987; Maheux et al 1994; Dunn et al 1997; Sator, Sator, et al 2001). A large retrospective multi-center study, NHANES I, conducted in 3825 women in the USA, showed that women under long-term substitution had one-third fewer wrinkles than non-substituted patients (Dunn et al 1997). Postmenopausal women with an HRT had significantly higher collagen content than untreated women (Brincat et al 1987).

One study examined the effects of three types of HRT in terms of skin aging in menopausal women (Sator, Schmidt, et al 2001): one group was given estrogen only via the transdermal route (Estraderm TTS® 50), the second group received estrogen by transdermal application in combination with vaginally applied progesterone (Estraderm TTS® 50 and 0.4 g progesterone vaginal suppository), and the third group was administered oral estrogen and vaginal progesterone (2 mg Progynova® and 0.4 g progesterone vaginal suppository). One group without treatment served as a control. Treatment was continued for 6 months. Skin surface lipids, epidermal skin hydration, skin elasticity, and skin thickness were measured at monthly intervals. Mean levels of epidermal skin hydration, elasticity, and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with HRT. Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while estrogen alone has a sebum-suppressive action (Zouboulis 2001). A comparison of skin hydration and elasticity in UV-exposed and non-exposed areas revealed no significant difference. This finding suggests that both photoaged and UV-protected skin benefit equally from HRT. These results were confirmed by animal tests using the skin of rats (Tsukahara et al 2001).

Although the majority of publications consider the influence of HRT on skin aging to be positive, there are some authors who doubt or reject any effect of hormone replacement on skin thickness, collagen synthesis, or elastin (Oikarinen 2000).

Alternatives: phytohormones

The estrogen-like effects of some plants were first described in 1926 (Loewe et al 1927). Phytoestrogens are classified in three categories: isoflavones, coumestans, and lignans. The most thoroughly examined group of substances are isoflavones, which display some similarity to the mammal estrogen molecule and are found, inter alia, in soy, beans, lentils, and red clover. Flavonoids are also contained in wine, especially red wine. The most important isoflavones are genistein and daidecin. The group also includes the precursors formonontein (for daidecin) and biochanin (for genistein). Coumestans only occur in the sprouts of legumes. Lignans have no influence on estrogen receptors. The structural similarity to 17β-estradiol explains the estrogen-like effects, which may be traced back to the interaction of these substances with the estrogen receptor (Wang et al 1996). Nutrition in Asian countries, with its large phytoestrogen content, is thought to be the reason why Asian women rarely suffer from climacteric symptoms. The biological potency of isoflavonoids is significantly inferior to that of synthetic estrogens (Markieicz et al 1993). When phytoestrogens are topically applied, they behave like estrogens by causing a proliferation of the epidermis, supporting collagen synthesis and reducing enzymatic collagen degradation.

A controlled open European multicenter study examined the effect of a cosmetic cream preparation including isoflavone (Novadiol®) on 234 women: maximum age 65 years, at least 3 years since menopause, no HRT or other substances affecting the skin aging process (Bayerl and Keil 2002). The length of therapy was 12 weeks. The isoflavone cream was applied two times daily (in the morning with a concentration of 0.0075% isoflavone and in the evening with a concentration of 0.015% isoflavone) on the face, neck, and one upper arm. The other arm was untreated and served as a control. Skin dryness and roughness were significantly improved at the treated areas by 32.9% and 22%, respectively, in comparison with the untreated skin areas. Facial wrinkles were significantly reduced by 22% and skin looseness was significantly reduced by 24%.

Summary of hormonal therapies

Numerous publications on the effects of sex hormones on the aging process are available today. Without claiming that HRT can or should ever be regarded as an independent treatment of skin aging, these findings are still interesting to note, considering that they indicate a beneficial effect of HRT on the skin despite the fact that the results of the “WHI-Study” (Rossouw et al 2002) and the “Million Women Study” (Beral 2003) have shown negative effects of HRT on other organs. What is clear is that HRT must be rejected when it is solely considered for the prevention of skin aging. As an additional benefit in the treatment of menopausal conditions provided by a dermatologist with sufficient experience in the discipline of endocrinology, however, it is a very effective instrument to control intrinsic skin aging.

While the topical application of hormones is certainly a suitable alternative to a systemic HRT, it must be ensured that such a treatment is also administered by a dermatologist experienced in endocrinology given that concentrations and application areas need to be observed in order to avoid systemic side effects.

Phytoestrogens, topical and systemic, appear to be an effective method in the treatment of intrinsic skin aging. However, further data are still required, especially from controlled studies on long-term results of systemic application.

Conclusion

An increasing number of products and procedures exists to promote youthful skin. First, a change of the lifestyle (eg, sun behavior, nicotine abuse, nutrition) of the patient must take place. Only then can other methods be used. A thorough knowledge of the properties (benefits, limitations, and complications) of the ever-expanding array of possibilities for rejuvenation of the skin is essential for any physician treating patients with cosmetic complaints.

Increasing aerobic capacity (VO2max) makes you live longer – it’s the telomere length again!

Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity

LaRocca TJ, Seals DR, Pierce GL.

Source

Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.

Abstract

Telomere length (TL), a measure of replicative senescence, decreases with aging, but the factors involved are incompletely understood. To determine if age-associated reductions in TL are related to habitual endurance exercise and maximal aerobic exercise capacity (maximal oxygen consumption, VO(2)max), we studied groups of young (18-32 years; n=15, 7 male) and older (55-72 years; n=15, 9 male) sedentary and young (n=10, 7 male) and older (n=17, 11 male) endurance exercise-trained healthy adults. Leukocyte TL (LTL) was shorter in the older (7059+/-141 bp) vs. young (8407+/-218) sedentary adults (P<0.01). LTL of the older endurance-trained adults (7992+/-169 bp) was approximately 900 bp greater than their sedentary peers (P<0.01) and was not significantly different (P=0.12) from young exercise-trained adults (8579+/-413). LTL was positively related to VO(2)max as a result of a significant association in older adults (r=0.44, P<0.01). Stepwise multiple regression analysis revealed that VO(2)max was the only independent predictor of LTL in the overall group. Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the “anti-aging” effects of maintaining high aerobic fitness.

2010 Elsevier Ireland Ltd. All rights reserved.

PMID:

20064545

[PubMed – indexed for MEDLINE]

PMCID: PMC2845985

Effective Treatments of Photodamage, photo-aging of the skin

Photodamage to the skin is due to extrinsic, ultraviolet radiation (UVR). There are currently two theories about aging: the first maintains that aging is genetically pre-determined,1 while the second suggests that aging is
related to the cumulative effects of environmental damage.2,3 Our perception of a person’s age and beauty mainly depends on the appearance of his or her skin.

Photoaging—Clinical and Histological Features

The clinical features that are associated with photodamage include dyspigmentation, laxity, yellow hue, wrinkling, vascular ectasia, thickened skin, and malignancies. In contrast, intrinsically aged skin shows signs of laxity, skin sagging, and wrinkles, but lacks evidence of UV damage. Histologically, photodamaged skin has undergone changes termed ‘heliodermatitis.’4 These changes include increased fibroblasts, flattened dermo-epidermal junction, atrophy, inflammatory infiltration, disorganized collagen fibers, and accumulation of amorphous elastincontaining material.2,5,6 Glogau classified photoaging into four types (see Table 1). Type I patients
with early photoaging are in their 20s to 30s and experience mild pigmentary changes, but no rhytides. Type II patients have moderate photoaging and are in their 30s to 40s, and have dynamic wrinkling and
dyspigmentation. Type III patients have advanced photoaging and are typically in their 50s. They have wrinkles at rest, dyschromias, vascular ectasias, and visible keratoses. Type IV patients have severe photoaging.
Generally, they are in their 60s to 70s, but may be younger. They have wrinkles covering the majority of the face, thickened coarse skin, a yellow-gray skin color, and a history of cutaneous malignancies.
Photodamage—Biology
There is evidence that reactive oxygen species (ROS) formation in response to UVR leads to photodamaged skin. Levels of antioxidants and enzymatic protection decline with age.7 Both UVA and UVB cause photodamage. UVB induces DNA mutations with subsequent carcinogenesis. UVA is believed to induce ROS, mitochondrial DNA damage, and carcinogenesis, and contributes to the aging process.8,9 The other biological effects of photodamage include dyschromias, such as lentigines and guttate hypomelanosis.2 Sunburn as a result of UV exposure is thought to be induced by nuclear factor-kappa B (NF-κB) pathways. UVR induces angiogenesis by increasing vascular endothelial growth factor (VEGF) production. An extremely important biological effect of UVR is immunosuppression—both local and systemic. After UVR exposure, Langerhan cells are depleted from the epidermis,10 which prevents the immune system from fighting photodamage.

Intrinsic Protection Against Photodamage
There are various responses and mechanisms utilized by the skin to counteract or reduce photodamage. Melanin production and distribution provide a protective mechanism against photodamage, as is evidenced by
a comparison of black and white skin, which have different levels of response to UVR exposure. UVR exposure induces protein (p)-53, which participates in the repair process, halting the cell cycle in the G1 phase
for DNA repair.11 There are conflicting reports regarding the role of tissue inhibitors of metalloproteinases (TIMP) after UV exposure. Human skin possesses antioxidants such as vitamin E, co-enzyme Q10 (CoQ10),
ascorbate, carotinoids, and enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxide. These antioxidants are  depleted as a result of excessive UVR exposure.12

Treatment Options for Photodamage
The treatment options for photodamaged skin can be categorized into a disease-prevention-based paradigm (see Table 2).13 Primary prevention refers to the reduction of risk factors before a disease has occurred.
Secondary prevention includes early detection, prevention, postponement, and attenuation of a clinical condition. Tertiary prevention is the treatment of an existing disease.

Photoprotection
Sun protection is both a primary and a secondary preventive measure  against photodamage. Sun protection can be achieved by the use of protective clothing, hats, sunglasses, etc. Photoprotective clothing is measured by its ultraviolet protection factor (UPF) value. For example, a clothing item with UPF 40–50 protects by transmitting only 2.6% of effective UVR.14 Sunscreens are designed to protect against UVB 290–320nm, UVA 320–400nm, UVC <290nm. The deeper penetrating UVA rays are mostly responsible for photoaging, while UVB rays are more responsible for photocarcinogenesis. In studies, sunscreens with both UVA and UVB protection have provided better protection than sunscreens with only UVB filters.
Sunscreens have different formulations worldwide (see Table 3). The ideal agent should be cosmetically pleasant, non-toxic and non-allergenic, effective against both UVA and UVB, photostable, and water-resistant.
Sunscreens have traditionally been divided into chemical or organic sunscreens that absorb UVR and convert it to heat, thus preventing UV interaction with skin. Sunblocks or inorganic agents have particles that reflect photons away from skin. UVB-absorbing sunscreens include p-aminobenzoic acid and its esters (padimate A and O), the cinamates, and salicylates. UVA sunblocks contain titanium dioxide and zinc oxide, and UVA-absorbing sunscreens include avobenzone (Parsol® 1789). Titanium dioxide provides excellent UVA II protection, but is less effective for UVA I. Parsol 1789 and zinc oxide have good UVA I protection, but lack UVA II protection.15 There are newer products on the market such as Mexoryl® and Helioplex™. Mexoryl has been shown to decrease DNA damage and instability in the melanocyte layer by reducing the formation of free radicals. It has also been shown to reduce the p53 mutations caused by UVA radiation.16 The new chemicals being developed provide efficient UVA coverage and better photostability.
Retinoids
Albert Kligman first reported the beneficial effects of tretinoin on photoaged skin of middle-aged women undergoing treatment for acne.17,18 Statistically significant improvement was noted in their appearance, surface roughness, fine and coarse wrinkling, mottled pigmentation, and sallowness in a clinical trial.19 Epidermal acanthosis and hypergranulosis regressed within the first 12 months of therapy.
Improvement of wrinkling corresponded to increased papillary dermis collagen deposition.21 Tretinoin treatment also appears to reverse histological changes of aging both in vivo and in vitro.

Tazarotene has also been shown to reduce roughness, wrinkling, mottled pigmentation, and pore size. There is convincing evidence that topical tretinoin repairs mild to moderate photodamage.
Antioxidants
Many studies have established a link between the application of topical antioxidants and the treatment of photoaging. These studies are small and most of the changes are considered to be associated with use of the antioxidant, and may not be statistically significant (p<o.05). Topical vitamin C has been shown to reduce erythema and sunburn cell formation. Vitamin C upregulates collagen and TIMP synthesis in human skin.22 CoQ10 is part of the mitochondrial electron transport chain. Topically applied, it has been shown to reduce wrinkles23 and is a potent antioxidant.
Oral soy isoflavinoids enhance the endogenous anitoxidant enzymes. Genistein and N-acetyl cysteines reduce collagenase upregulation after UV exposure. Gluconolactone has antioxidant properties and alphahydroxy
acids (AHA)-like effects. When taken orally, green tea propophenols inhibit metalloproteinase expression after UV exposure.
N-furfuryladenine is a synthetic plant growth hormone with antioxidant properties.24 The list grows daily and has led to a booming cosmetic industry known as ‘cosmeceuticals.’
Growth Factors and Cytokines
A fructose-rich polysaccharide, ‘FROP3,’ increased glycosaminoglycan  synthesis by fibroblasts.25 In a pilot study, a cream containing FROP3 showed a 10–15-year decrease in apparent age after four weeks of use.

Chemical Peels

Chemical peels with AHAs, salicylic acids, trichloracetic acid, and phenol are used to treat photodamage and mottled pigmentation. The peels are classified as superficial, medium, or deep correlating to the depth of
injury induced.27 Glycolic acid is an AHA that reduces fine wrinkling.  It has also been shown to thin the epidermis and induces dermal collagen synthesis.

Cutaneous Resurfacing Techniques
Microdermabrasion
This process exfoliates and ablates the superficial dermis. Microdermabrasion activates a closed, dermal wound-healing process and increases cytokines, matrix metalloproteinases (MMPs), and type I procollagen messenger (m)-RNA production.29 Significant increases in papillary dermal thickness and improved elastin organization have been observed.

Lasers, Light Sources, and Radiofrequency Devices
Ablative Laser Systems
These systems include CO2 lasers and erbium-yttrium aluminium garnet (Er:YAG) lasers. The CO2 laser was once the gold standard in facial resurfacing, and can produce dramatic improvements in skin tone, wrinkle severity, and atrophic scar depth.31–34 The Er:YAG was developed to reduce the morbidity associated with CO2 and has demonstrated comparable results. The biochemical changes seen with ablative resurfacing include increased interleukin (IL)-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, type I and III procollagens, and MMPs.
Non-ablative Laser Systems
Treatment of photodamaged skin with non-ablative lasers has become increasingly popular and effective. These devices induce target-specific rejuvenation and non-ablative skin remodeling. The targets are three-fold:
reduction in vascular anomalies, pigment anomalies, and static fine wrinkles.36–38 Various lasers systems have been used for this purpose and will be briefly discussed. Hemoglobin is the primary target, and melanin or
pigment the secondary target, of 532nm lasers. The main benefit is for facial telengiectasis, but it is also good for lentigines and tattoos.
Flashlamp pulse dye (FPD) lasers are the gold standard for vascular lesions, and operate at 585nm/595nm. Success with dermal remodeling has recently been reported.40 The current trend is to use the longer wavelength of 595nm for less severe vascular bruising. Cooling is accomplished by a dynamic cooling device, e.g. the Candela V Beam™, the Cynosure V Star, or the NLite laser.40–43 Quality-switched (QS) lasers deliver an ultra-short pulse duration, which is critical for target disruption. Primary wavelengths used are 532, 694, 755, and 1064nm. The first three treat vascular and pigmented lesions, and the fourth treats dermal pigments such as tattoos and melanin. The QS 1064 has shown efficacy in dermal collagen deposition and remodeling.44,45 Long-pulsed (LP) near-infrared lasers include the LP 755, 800, and 1064nm models. They target hemoglobin and melanin. If cooling is inadequate, it can lead to full-thickness scar formation.46 LP mid-infrared lasers do not cause melanin or hemoglobin absorption; instead, they target water. New collagen synthesis without epidermal damage has been reported.47–49 The devices include Cool Touch® 1320nm neodymium-doped (Nd):YAG, Candela Smoothbeam 1450nm Diod laser, and Aramis 1540nm Er:Glass laser.

Broadband Light Sources
Broadband light sources are versatile and have proved to be effective clinically and histologically,49–52 and the intense pulsed light (IPL) version is the most studied.53–55 These devices emit light of 515–1200nm that can
be manipulated with various filters. Photothermolysis is obtained via absorption by deoxyhemoglobin, the chromophore at 600–750nm. IPL systems can achieve photorejuvenation by improving mottled pigmentation, telengiectasis, and skin texture. The data also support long-lasting effects of up to five years.56 It is anticipated that after three to five treatments improvement in pigment, vasculature, pore size, and fine wrinkles will occur. Examples include Lumenis Quantum, DDD  Ellipse, Palomar Medilux™, and Starlux®. Fractional Photothermolysis A hybrid novel technology combining ablative and non-ablative resurfacing is fractional photothermolysis. The technique has been validated by many studies and supporting results.57 A mid-infrared laser at 1550nm is used with vertical microthermal columns of 100–160μm width, which can be adjusted for 300–700μm penetration.58 The pixilated laser leaves 70% of the treated area undamaged and promotes rapid healing. There is a reported patient-to-patient consistency in collagen remodeling and epidermal regeneration. Examples include the Reliant Fraxel® Laser, Palomar’s Star Lux, and Cynosure’s Affirm.
Radiofrequency and Infrared Heating
The first non-surgical treatment to address the soft-tissue redundancy has been radiofrequency (RF) with Unipolar RF (ThermaCool TC, Thermage, Inc., Hayward, California).59–62 RF does not target a specific  hromophore; instead, it produces controlled volumetric heating of the deep dermis with subsequent collagen degeneration and tissue shrinkage. Unipolar RF carries a risk of subcutaneous atrophy. More recently, bipolar radiofrequency has been used. Syneron’s Aurora is a widely used bipolar device.

Photomodulation
Photomodulation utilizes non-thermal neo-collagen synthesis. Most widely used are light-emitting diodes (LEDs) such as Gentlewaves® 590nm LED (LightBioScience LLC, Virginia). LED treatments are administered
immediately after fraxel or photorejuvenation treatment.

Soft-tissue Augmentation by Fillers
Restoration of facial volume and contour by fillers has become a popular and effective treatment of photoaged skin. Fillers are used to either correct pre-existing defects or augment existing facial structures. There is a plethora of available filling substances and the choice of the filling material depends on many factors.
Autologous fat is one of the oldest fillers and is still widely used. Its advantages include high volume, ease of use, and low cost, and, being autologous, it causes no reactions. Fat is excellent for nasolabial folds, marionette lines, and cheeks. It is transplanted to the face after being harvested from another region of the body, such as the abdomen or thighs.
Bovine collagens have been available for many years, e.g. Zyderm I, Zyderm II, and Zyplast. They have been used for depressed scars, nasolabial folds, and lips. Two of the disadvantages are adverse reactions and a need for skin tests prior to administration.
Synthetic human collagens are available i.e. CosmoDerm I® and CosmoPlast®, and the advantage is avoidance of reactions. All collagens are limited by longevity, and rarely persist six months after injection. They can
be used for many sites, but are most often used for lip augmentations. A new collagen called Evolence™ promises one-year longevity.
Hyaluronic acid (HA) materials are derived from rooster combs or bacterial sources.63 They are less immunogenic than other methods, as HA is identical across species. It is a naturally occurring polysaccharide, and is the most plentiful glycosaminoglycan in the dermis. It is negatively charged, and able to hold large amounts of water. Compared with bovine collagen, no signs of incompatibility are noted in HA products.64 These products last for six to 12 months and undergo isovolumic degradation. There are no skin tests required, and there is no overcorrection with the injections. Many products are available, including Hylaform®, Achyl®, Restylane®, Dermalive®, Perlane®, Hyacell®, Juvederm®, and Viscontour®.
The products are used for various conditions such as facial rhytides and contouring, nasolabial folds, patulous scars, and lip volumization. These products are not suitable for dynamic rhytides, ice-pick scars, striae, or actinically damaged lips. Absolute contraindications include
hypersensitivity, history of anaphylaxis, and implantation for breast, muscle, bone, and tendon augmentation.
Long-lasting filler agents include Sculptra™ (containing poly-L-lactic acid), Radiesse® (calcium hydroxylapatite), and silicon. Sculptra is approved by the US Food and Drug Administration (FDA) for treating HIV-lipoatrophy for high-volume correction of the face, and it is easy to use. Often, several treatment sessions are required to obtain the desired effect. Radiesse is approved by the FDA for facial rhytids in the nasolabial folds. It is similar to HA in many ways, but the injection technique is slightly deeper. Radiesse is not yet recommended for injection into the lips.
Photodynamic Therapy
Actinic keratosis (AK), a pre-malignant condition, is a feature of chronically
photodamaged skin. Topical photodynamic therapy (PDT) with aminolevulonic
acid (ALA) (Levulan Kerastick®, DUSA, Wilmington, Massachusetts) and
methyl-aminolevulonic acid (MAL) (Metvix®, Galderma, Watford, UK) is an
effective treatment option for AK and also offers excellent cosmesis.65
Recent studies show that PDT induces photochemo-rejuvenation of some
manifestations of photoaging. Both ALA and MAL have been used in
conjunction with blue light, IPL, and other laser wavelengths for
treatment of AK. Many of the studies have also shown other benefits of
PDT for photodamaged skin, including improvement in skin texture,
global quality, fine wrinkling, and sallowness.66 In recent studies,
ALA–IPL–PDT has shown superiority over IPL alone in reducing mottled
pigment and fine wrinkles.67 Clinical findings indicate that Levulan with
blue light and Metvix with red light induce a high clearance of AKs, as
well as improved fine wrinkles, texture, and sallowness, whereas IPL–PDT
assists in improving telengiectasis and erythema.68 So far, the mechanism
of action of PDT in photochemo-rejuvenation is largely unknown.

Botulinum Toxin A
In 2002, botulinum toxin A was approved by the FDA for treatment of glabellar lines. The toxin blocks the post-synaptic release of acetylecholine, thereby inhibiting muscle contraction. Botulinum toxin does not directly
reverse photodamage, but delivers a rejuvenated look by relaxing muscles causing dynamic wrinkling of the face. The effect typically lasts for between three and nine months.

Fluorouracil and Imiquimod
Both fluorouracil (5-FU) and imiquimod have been successfully used to treat AK, Bowen’s disease, and superficial basal cell carcinomas. All of these conditions are as result of UV photocarcinogenesis and a part of chronically photodamaged skin. The treatments of AK result in excellent cosmesis and prevention of skin cancers.
Conclusion
Effective treatment of photodamage is complex. Cosmetic treatments often target complaints of discoloration or wrinkling. Medical treatments target carcinogenesis. The number of healthy older patients is increasing
and thus the demand for better, longer-lasting treatments is on the rise. It is an exciting time in the field of treatment of photodamage.

Vitamin D – an anti-aging supplement?

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women

J Brent Richards, Ana M Valdes, Jeffrey P Gardner, Dimitri Paximadas, Masayuki Kimura, Ayrun Nessa, Xiaobin Lu, Gabriela L Surdulescu, Rami Swaminathan, Tim D Spector and Abraham Aviv

ABSTRACT

Background: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.

Objective: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.

Design: Serum vitamin D concentrations were measured in 2160 women aged 18–79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.

Results: Age was negatively correlated with LTL (r = –0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.

Conclusion: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.

Telomere shortening and aging – understanding cellular aging

What is a Telomere?

A chromosome is a long strand of DNA. At the end of a chromosome is a telomere, which acts like a bookend. Telomeres keep chomosomes protected and prevent them from fusing into rings or binding with other DNA. Telomeres play an important role in cell division.

What Happens When a Cell Divides?

Each time a cell divides, the DNA unwraps and the information in the DNA is copied. The process does not copy all of the DNA information – the telomeres are not copied. When the cell is finished dividing, the DNA comes back together. The telomeres lose a little bit of length each time this happens.

Why Do They Get Shorter?

When a cell divides and copies DNA, the strands of DNA get snipped to enable the copying process. The places that are snipped are the telomeres. Since the telomeres do not contain any important information, more important parts of the DNA are protected. The telomeres get shorter each time a cell divides, like a pencil eraser gets shorter each time it’s used.

Can Telomeres Become Too Short?

Yes. When the telomere becomes too short, essential parts of the DNA can be damaged in the replication process. Scientists have noticed that cells stop replicating when telomeres are shorter. In humans, a cell replicates about 50 times before the telomeres become too short. This limit is called the Hayflick limit (after the scientist who discovered it).

How Does All This Affect Aging?

Researchers can use the length of a cell’s telomeres to determine the cell’s age and how many more times is will replicate. This is important in anti-aging research. When a cell stops replicating, it enters into a period of decline known as “cell senescence,” which is the cellular equivalent of aging. However, another reason telomeres are important is cancer.

Cancer? Why Are We Talking About Cancer Now?

Cancer is a condition in which certain cells in your body stop dying. Every system in your body is carefully balanced to allow for cells replicating and dying. If cells stop dying and keep replicating, the balance is disrupted and there are too many of one kind of cell. Groups of these cells form tumors. Researchers believe that cancer cells are creating an enzyme called telomerase, which prevents telomere shortening.

Where Does Telomerase Come From?

Every cell in your body has the genetic code to make telomerase, but only certain cells need to produce this enzyme. White blood cells and sperm cells, for example, need to have telomere shortening switched off in order to make more than 50 copies of themselves through your lifetime. In advanced cancer, the cancer cells also seem to be producing telomerase, which allows them to continue to replicate without dying.

Telomere Shortening and Aging

In population level studies, researchers have shown that older people have shorter telomeres. Eventually, the cells with shorter telomeres can no longer replicate and, taken over time and lots of cells, tissue damage and the dreaded “signs of aging” can show up. Most cells can replicate about 50 times before the telomeres are too short. Some believe that telomeres are the “secret to longevity” and there are circumstances in which the telomeres will not shorten. Cancer cells, for example, don’t die (which is the main problem) because they switch on an enzyme called telomerase, which adds to the telomeres when cells divide. Some cells in your body need to do this (stem cells and sperm cells, for example) because they need to replicate more than 50 times in your lifetime.

Does It Happen to Everyone?

No — and that’s a big surprise. Researchers in Sweden found out that some people’s telomeres do not necessarily get shorter over time. In fact, they found that some people’s telomeres even get longer. This variation at the individual level was hidden by prior studies that averaged results over large population.

What Does Non-Shortening Telomeres Mean?

In the study, 959 individuals donated blood twice, 9 to 11 years apart. On average, the second samples had shorter telomeres than the first. However, around 33% of the people had either a stable or increasing telomere length over a period of around 10 years. What does this mean? Nobody knows. It could be that those people have an amazing cellular anti-aging mechanism or it could be that they have an early sign of cancer (researchers tried to rule this out) or it could be fairly meaningless. What we do know for sure is that aging is a lot more complicated than simply looking at the shortening of telomeres.

Que es CJC-1295? (GRF 1-29) (en español) liberadora de hormona de crecimiento de larga duración

COMPRA CJC-1295 con DAC (drug affintiy complex) 2 mg de nosotros $49 superhumangear@gmail.com

CJC-1295 es un peptídico análogo del GHRH (growth hormone releasing hormone) o hormona liberadora de hormona de crecimiento. Por la forma en que CJC-1295 es manipulada su vida media, o periodo de semidesintegracion, fue extendida de 7 minutos a mas de 8 días!

Debido a la extremadamente larga vida media del CJC-1295 es plausible usar este peptídico unas ves a la semana y adquirir resultados extraordinarios. Es recomendado usar media dosis dos veces por semana para mantener los niveles de suero estables en su clímax y obtener resultados óptimos.

Varios experimentos han sido conducidos para comprobar la efectividad del CJC-1295 en vivo y el Journal of Clinical Endocrinology & Metabolism (Dario de Endocrinología Clínica & Metabolismo), informo dosis–dependiente incrementos del promedio de concentración de plasma GH (growth hormone) o hormona de crecimiento, multiplicados por 2 a 10 por mas de 6 días e incremento de concentración de IGF-1 (insulin like growth factor 1) o factor de crecimiento similar a insulina 1, multiplicados por 1.5 a 3 por 9 a 11 días después de solo una inyección.

Tambien han comprobado el promedio de vida media siendo 5.8 a 8.1 días y después de dosis múltiples demostró el promedio de los niveles de IGF-1 se mantuvo sobre la línea de fondo por asta 28 días después! En ningún grupo fueron reportadas serias reacciones adversas.

GH (hormona de crecimiento) es compuesta de una secuencia de 191 amino ácidos y es producida en el cuerpo humano por la glándula pituitaria. Existen niveles altos de esta hormona especialmente durante la adolescencia donde estimula el crecimiento de tejidos, deposición de proteínas, y la descomposición de almacenes de grasa subcutánea.

GH estimula el crecimiento de la mayoría de los tejidos, ante todo debido al incremento en número de células en vez del incremento en tamaño de estas. La transportación de amino ácido también incrementa al igual que la síntesis de proteína. Todos estos efectos son causados mediante el IGF-1, una hormona altamente anabólica producida en el hígado y otros tejidos en respuesta al GH.

GH también estimula hidrólisis de triglicéridos en tejido adiposo, usualmente produciendo una notable desminuida en cantidad de grasa corporal durante tratamiento. También incrementa el rendimiento de la glucosa en el hígado y provoca resistencia a la insulina bloqueando la actividad de esta hormona en ciertas células causando un cambio en la cual grasas se favorecen mas como recursos primarios de combustible, aumentando aun mas la perdida de grasa corporal.

Sus efectos estimuladores de crecimiento también fortalecen tejidos conectivos, cartílago, y tendones. Este efecto debería desminuir la susceptibilidad a lesión dado al entrenamiento pesado de pesas.

IGF-1 (factor de crecimiento similar a insulina 1) es una hormona peptídico compuesta de 70 amino ácidos y es encontrado naturalmente en el cuerpo humano. IGF-1 a demostrado incrementar la velocidad y el alcance de la reparación muscular después de lesión e incrementa la velocidad hipertrófica o crecimiento muscular del entrenamiento físico. No solo las existentes fibras musculares son reparadas más rápido, IGF-1 es responsable por la hiperplasia, o incremento en la cantidad de fibras musculares.

Hiperplasia es el santo gremial de los beneficios de la mejor acción del rendimiento, y ocurre cuando fibras musculares se dividen, creando más fibras musculares. Hipertrofia es simplemente el incremento del tamaño de las existentes células musculares y ocurre através del entrenamiento con resistencia, o pesas y uso de esteroides anabólicos. Hiperplasia mas hipertrofia es equivalente a una increíble nueva raza de atleta.

Otro beneficio bastante positivo del CJC-1295 es su habilidad de estimular SWS (slow wave sleep) o sueño de ondas lentas. Sueño de ondas lentas es conocido como sueño profundo y es la parte del sueño responsable por los más alto niveles de hipertrofia y retención de memoria muscular. Este tipo se sueño es significantemente desminuido en personas de tercera edad y en gente con tendencia a ejercitar en la tarde. Este peptídico tiene una proporción de benéfico a efecto segundario que supera a cualquier otro actualmente siendo vendido y seria una gran adición al régimen de entrenamiento o terapia post -ciclo de cualquiera.

>Antiaging treatments have been legally prescribed for approximately 30 years

>

Well, it seems like our best selling anti-aging products are nothing new, according to this article:

Antiaging treatments have been legally prescribed for approximately thirty years
Ukraintseva SV, Arbeev KG, Michalsky AI, Yashin AI.

Max Planck Institute for Demographic Research, 18057 Rostock, Germany. ukraintseva@cds.duke.edu
Abstract

There is an interesting divergence between the achievements of geriatrics and gerontology. On the one hand, during the last 30 years physicians in many developed countries have successfully prescribed several medicines to cure various symptoms of senescence. On the other hand, the influence of such medicines on human life span practically has not been studied. The most common of the relevant medicines are nootropic piracetam, gamma-aminobutyric acid (GABA), selegiline, Ginkgo biloba, pentoxifylline, cerebrolysin, solcoseryl, ergoloid, vinpocetin, sertraline, and estrogens, among others. Available data from human clinical practices and experimental animal studies indicate that treatments with these drugs improve learning, memory, brain metabolism, and capacity. Some of these drugs increase tolerance to various stresses such as oxygen deficit and exercise, stimulate the regeneration of neurons in the old brain, and speed up the performance of mental and physical tasks. This means that modern medicine already has “antiaging” treatments at its disposal. However, the influence of such treatments on the mean and maximal life span of humans, and on the age trajectory of a human survival curve has been poorly studied. The increase in human life expectancy at birth in the second half of the last century was mostly caused by the better survival at the old and oldest old rather than at the young ages. In parallel, the consumption of brain protective and regenerative drugs has been expanding in the elderly population. We provide evidence in support of the idea that the consumption of medicines exerting antiaging properties may contribute to the increase in human longevity.

PMID: 15246996 [PubMed – indexed for MEDLINE]

>GSH glutathione, the master antioxidant (Tationil, TAD600, Ridutox)

>
GSH glutathione, the master antioxidant (Tationil, TAD600, Ridutox) – skin smoothing-glowing-whitening, cellular rejuvenation

1. it is a protein (amino acid) molecule which is important as our body antioxidant, immune system booster and detoxifier
2. it presents in every cell to promote normal function as maintaining the immune system
3. one of the master antioxidant that mostly found in liver
4. it eliminates toxic compound (such as Paracetamol) in liver
5. it reconstitutes vitamin C and E which is being oxidized
6. combine taking with vitamin c injection greatly enhance your immunity, reduces tiredness, more youthful skin and stay healthy
7. fights against the cancer, heart disease, premature aging, autoimmune disease and chronic illness

Interaction: No known interaction, individual with liver malfunction is supposed to take this product. Pregnant and lactating women are not supposed to take the injection and other same kind of supplementary.

Dosage and method: 1-3 ampoules weekly by intravenous or intramuscular method.

Frequently Asked Questions:

1. What is glutathione? It is an important chemical that acts as a powerful antioxidant to preserve and protect the brain and other body tissues by protecting them from the damage of free radicals. It also acts to recycle vitamin C & E which also reduce free radicals.

2. What studies prove it work or are there any studies that prove it works?
The landmark study was done by the Department of Neurology, University of Sassari, Italy in 1996. In this study all patients improved significantly after glutathione therapy with a 42% decline in disability.

3. What is glutathione used for? It has been used to treat all symptoms of neurodegenerative diseases such as Parkinson’s, Alzheimer’s, multiple sclerosis, stroke, ALS, irritable bowel, and chronic fatigue.

4. What improvement in symptoms can one expect? Many patients have had profound improvements with respect to reduction of rigidity, increased mobility, improved ability to speak, less depression, and decreased tremor. Glutathione has the added benefit of protecting the brain from free radical damage, thus possibly slowing the progression of the underlying illness.

5. How long can a person take glutathione and how long will the effect last after I stop using it? It can be taken permanently. In the 1996 Italian study the therapeutic effect lasted 2-4 months after therapy was stopped.

6. How long has this treatment been used. Physicians have been using glutathione infusions for at least 30 years, probably longer.

7. How is the treatment given? It is given intravenously in the arm by IV push over 10 to 15 minutes usually three times a week in a physician’s office.

>Treatment of aging neck with Lipostabil

>BUY LIPOSTABIL FROM US: $5 /5 ml amp superhumangear@gmail.com

Treatment of aging neck with Lipostabil (phosphatidylcholine 5% with deoxycholate)

J Drugs Dermatol. 2009 Oct;8(10):937-9. Rittes PG, Rites C.

Clinica Dermatológica Patrícia Rittes, São Paulo, Brazil. prittes@terra.com.br

Abstract

BACKGROUND: The lower third of the face and neck have distinct changes that occur with aging: the lost of the perfect jaw line due to laxicity of skin and fat deposits associated with “turkey neck.” Theses changes can be globally and drastically addressed with traditional rhytidectomy, however patients increasingly seek less invasive procedures. Injections with Lipostabil Endovena-a mixture of phosphatidylcholine and deoxycholate, a bile salt-have been used to reduce unwanted, accumulated fat. Recent in vivo investigations indicate that phosphatidylcholine and deoxycholate cause adipocyte lysis, an inflammatory processes and fibrosis. These reactions lead to skin retraction.

OBJECTIVE: This paper reports the author’s experience treating aging neck using Lipostabil Endovena.

RESULTS: Laxity of the skin improved in all patients. A marked reduction in double chins was noted and the jaw line was reconstructed. Adverse effects, including transient burning, erythema and local swelling were present in all patients, but resolved themselves without intervention.

CONCLUSION: The author’s clinical experience supports the conclusion that Lipostabil Endovena treats subcutaneous fat tissue and that fibrosis after the inflammatory process retracts the skin, tightening the injected area and improving the aging neck.

PMID: 19852123 [PubMed – indexed for MEDLINE]