Colostrum improve the growth rate of many cell types

Colostrum
Colostrum is the initial milk or “first milk” that is produced by mammals (including humans) immediately following parturition. As expected, colostrum was more effective than milk with the total lipid, linoleic acid, linolenic acid, ganglioside, and glycolipid contents were higher in colostrum when compared to milk. In addition, with further analysis, the fat globule fraction provided the strongest stimulation for wound repair that contained Epidermal Growth Factors. The milk fluid produced by all female mammalian species after birth has the function to meet the complete nutritional requirements of the neonate and, at the same time, provide all of the biochemical needs and support the many biological functions of the immature newborn to help the newborn survive and develop. Starting in the 1980s and through the mid-1990s, supplemented cell culture medium with milk or colostrum was reported to improve the growth rate of many cell types including skin (fibroblasts). Peptides from milk protein hydrolysates improved the growth of human keratinocytes in culture. Medium supplemented with 300 μg/mL for 12 days where the average molecular weight of 800 Da containing a high concentration of amino acids promoted the growth of the keratinocytes by 108% (Vollmer et.al, 2018). Colostrum is the only known natural source of the enzyme, telomerase, which may help to slow down the aging of DNA. In fact, there is evidence that short telomeres and a lack of telomerase can exert a longevity-promoting effect via prevention of cancer (Hornsby et.al, 2007). Colostrum also includes EGF and IGF-1, which are known to assist in the repair and regeneration of cells. EGF and IGF-1 play essential roles in wound healing, which makes colostrum an important potential adjunct to the skin’s repair following a surgical cosmetic procedure. Let’s not forget about the lactoferrin in colostrum, either. Lactoferrin helps manage the immune response in the skin cells, which means supplementing with lactoferrin may potentially help a person increase his or her skin’s anti-inflammatory response (Blog sovereignlaboratories.com).

Selenium
Selenium (Se) is an essential trace element in the human body and plays an important role in the body via selenoprotein, which contains selenium. Selenoproteins (glutathione peroxidase, thioredoxin reductase, methionine sulfoxide reductase-1 and endoplasmic reticulum-selenoproteins, etc.) have antioxidant effects and are involved in regulating antioxidant activities (Cai et.al, 2018). Se and the selenoproteins are essential for keratinocyte function and skin development. A lack of seleno-enzymes in the mouse epidermis leads to abnormalities in the skin and hair follicles, premature skin aging, and premature death. Additionally, several studies have shown that Se pretreatment can drastically protect keratinocytes, melanocytes, and fibroblasts from UV-induced cytotoxicity.  Low doses of Se were very potently protective against UVA-induced cytotoxicity in young keratinocytes, whereas the aged keratinocytes require four times more Se than the young keratinocytes to be protected from UVA-induced cytotoxicity (Favrot et.al, 2018; Jobeili et.al, 2013). Se protects keratinocyte stem cells (KSCs) against senescence via preservation of their stemness phenotype through adhesion to the basement membrane (Jobeili et.al, 2013). Wang et. al, 2017 showed that Vitamin C (250 mg/kg), vitamin E (250 mg/kg) and Se (0.2 mg/kg) exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin-induced diabetes (65 mg/kg) in Swiss albino rats.

Hyaluronic Acid
Hyaluronic acid (HA) is part of the body’s connective tissues and is known to cushion and lubricate. Aging destroys HA. Diet and smoking can also affect your body’s level of HA over time.  Skincare products with HA are most frequently used to treat wrinkled skin although they don’t replace anything the body has naturally lost. These are very effective moisturizers (WebMD. Understanding Skin Care Products). UV radiation damage causes initially a mild form of wound healing and is associated at first with an increase of dermal HA. As little as 5 min of UV exposure in nude mice caused enhanced deposition of HA, indicating that UV radiation-induced skin damage is an extremely rapid event. The initial redness of the skin following exposure to UV radiation may be due to a mild edematous reaction induced by the enhanced HA deposition and histamine release. Repeated and extensive exposures to UV ultimately simulate a typical wound healing response with deposition of scarlike type I collagen, rather than the usual types I and III collagen mixture that gives skin resilience and pliability (Papakonstantinou et.al, 2012). HA-based formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration. HA, alone or in combination with lidocaine and other co-agents, showed promising efficacy in skin tightness and elasticity, face rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity, and tear trough rejuvenation (Bukhari et.al, 2018). Sparavigna et.al, 2019 reported significant improvement of wrinkles’ grade around the eyes, vertical lip lines and wrinkles’ severity of nasolabial folds after the first injection and the effect increased after the second injection. Aging/photoaging grade and surface microrelief improved 2 months after the first injection procedure. The treatments were very well tolerated by the volunteers as determined by the self-grading score. Lee et.al, 2019 reported that Cross-linked hyaluronic acid (CLHA) patches were not an irritant, whereas a clinical study showed that the application of single CLHA patches significantly improved skin hydration at the periorbital region for 3 days and at the nasolabial fold for 6 days. Patch application also improved superficial wrinkles at the periorbital region for 3 days and at the nasolabial fold for 1 day. The absence of side effects indicated that the application of these CLHA microstructure patches is both safe and convenient for moisturization and anti-wrinkle effects. Jeon et.al, 2019 reported that CTP-EGF has superior ability, compared with natural EGF, to permeate the skin and induce HA synthesis and collagen formation. Thus, it has great potential to be used in cosmetics and therapeutic agents to improve wrinkles and the health of the skin. There exist many different types of HA gel fillers that differ in their HA concentration, particle size, cross-linking density, duration, and presence of lidocaine. High-density, large-particle fillers are recommended for deep dermal injections while low-density, small-particle filters are recommended for fine lines. HA gel is used by several healthcare professionals include the plastic surgeon, primary care provider, dermatologist, nurse practitioner and internist to enhance cosmesis. HA fillers are injected to restore volume lost due to age or disease, provide facial contour, and help maintain a youthful appearance. Filler injection has become one of the most commonly performed procedures in a dermatology cosmetic practice (Walker et.al, 2019).

Poly-L-lactic acid
Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss. Polydioxanone Cog thread and poly-L-lactic acid (PLLA) thread have been used clinically for lifting and antiaging purposes (Palm et.al, 2009). PLLA is an effective treatment for patients seeking to correct volume loss due to aging. Although the US FDA has approved PLLA for use in people with the HIV in 2004, it is well-suited for patients seeking cosmetic treatment. By 2009 PLLA was FDA-approved for the correction of nasolabial fold contour deficiencies and other lines and wrinkles. There have since been limited but promising results with off-label use of PLLA for non-facial volumization as well, including the hands, neck/décolleté, abdomen, and gluteal area (Jabbar et.al, 2017). PLLA is a safe, biodegradable volumizer used to reverse the signs of aging by gradually correcting volume loss. Patients should be aware of possible adverse reactions during the course of treatment (Palm et.al, 2009). Injection of PLLA in the deep dermis or subcutaneous tissue may cause an immediate augmentation of the treated tissue. This is a temporary but immediate response that is due to tissue edema and fluid from the reconstitution of the product. It will resolve within 2 to 3 days after injection. Once the carrier substance is absorbed, the poly-L-lactic acid particles induce an inflammatory response through phagocytosis by tissue macrophages. This is a similar process to suture reabsorption in the skin. The inflammatory response breaks down the poly-L-lactic acid into lactic acid monomers and is then metabolized to carbon dioxide and water while stimulating the production of new collagen type-I fibers in the skin. Approximately half of the product is digested within 6 months. The duration of action is 12 to 24 months (Sickles et.al, 2019). Kapicioğlu et.al, 2019 reported that PLLA and Cog sutures were effective in facial rejuvenation (studied in female rats); both increased dermis thickness and stimulated collagen production. Repeated PLLA treatments may improve skin quality in a time-dependent manner. Pigmentation, erythema, and pore size were significantly decreased, whereas radiance and smoothness were significantly increased at 12 months. No treatment-related adverse events occurred. Repeated PLLA treatments may improve skin quality in a time-dependent manner (Bohnert ET.AL, 2019). The process of hydration, loss of cohesion and molecular weight, and solubilization and phagocytosis of PLA by the host’s macrophages degrades PLA into lactic acid microspheres and eliminates CO2 by way of respiratory excretion. Crystals are left behind to stimulate collagen and a granulomatous reaction. This inflammatory reaction elicits resorption and the formation of fibrous connective tissue about the foreign body, causing dermal fibroplasia that leads to the desired cosmetic effect [2]. Kim et.al, 2019 reported that powdered polydioxanone injection induces collagen formation more effectively than PLLA injection (Ganceviciene et.al, 2012).

Hormone Replacement Therapy
In postmenopausal women, dermal collagen decreases, and skin becomes thinner (Warren et.al, 2015). Hormone replacement therapy (HRT) has been shown to be effective in alleviating menopausal symptoms. However, its use is controversial owing to potential health risks, such as thromboembolism and cancer. Bioidentical hormone therapy has also been used by dermatologists for its anti-aging effects on the skin, but little is known about the efficacy and side effects of bioidentical hormones in this field (Borda et.al, 2019). Women’s Health Initiative (WHI) study showed a higher risk for breast cancer, stroke, cardiovascular disease, and thromboembolic events with combined treatment of estrogens and progestin. Synthetic progestins mostly used worldwide include medroxyprogesterone acetate (most frequently used in the US), norethindrone acetate, cyproterone acetate, norgestimate, norgestrel, and dydrogesterone (Samaras et.al, 2014). The HRT impact on skin thickness and dermal density was demonstrated early when estrogens were initially administered to postmenopausal women. Such replenishment therapy was therefore considered as an attempt at alleviating in part skin atrophy and xerosis in postmenopausal women. Indeed, HRT controls in part the dermal thickness and laxity, and the collagen content and density, as well as the tissue mechanical reactivity, to stress (Piérard et.al, 2013). Physicians and patients have become extremely reluctant concerning HRT following the WHI study. Numbers of HRT prescriptions in the US rose from 58 million in 1995 to 90 million in 1999, corresponding to 15 million women per year. The numbers remained stable through to 2002. Within 3 months after publication of the results of the WHI study, prescriptions of various formulations of combined estrogens and progesterone dropped by 33% to 66% (Samaras et.al, 2014). Vinogradova et.al, 2019 reported an association between the risk of venous thromboembolism and different types of HRT. Transdermal treatment was the safest type of hormone replacement therapy when the risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations. Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal resulted in a significant decrease in LH. Oral estradiol, though not transdermal estradiol, increased serum high-density lipoprotein, thyroxine-binding protein, and growth hormone binding protein (Jospe et.al, 1995). Applying estrogen cream to the skin after menopause improves the external appearance of facial skin (Warren et.al, 2015). There is strong evidence that transdermal estradiol has a cardioprotective effect (Botelho et.al, 2014). Due to their lack of first-pass hepatic metabolism, transdermal products achieve clinical benefits while minimizing patient exposure to estrogens, which is consistent with the most recent clinical guidelines (Kopper et.al, 2009). Also, by increasing skin collagen content, and increasing acid mucopolysaccharides and HA, estrogen therapy encourages the growth and development of vaginal epithelial cells which make up the thick layers of the vaginal wall, and condone a moist, supple and elastic environment (Jenifer et.al, 2015). Botelho et.al, 2014 reported that nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. Abdi et.al, 2017 also concluded that the use of transdermal nano-formulations in hormone therapy can relieve climacteric symptoms and prevent other postmenopausal symptoms.

CONCLUSION
As more and more anti-aging and antioxidant skincare products flood the market, there is growing concern about definitions and experimental proof of   effectiveness. The physician has an important role in understanding which treatment options are appropriate for mild, moderate, and severe photoaging, and in educating patients on the risks and benefits of each. The choice of the right active compounds, the verification of their activity inside a cosmetic formulation, their   stability and synergistic effects should be the first step toward   the creation of modern and effective products.  To be active inside the skin, the antioxidants have to penetrate into the living layers of the skin, where free radicals are generated and should be effective against   ROS.  This is possible only if the topically applied formulation holds the potential to be effective. Moisturizing and emollient products are gaining increasing importance in dry skin treatment, maintenance of daily care of normal skin as well as ancillary therapy of many skin diseases. Consumers are nowadays more focused on their health and appearance. As a result, there has been an increasing demand in topical antiaging formulations with natural and nutraceutical ingredients. Novel and innovative delivery systems are transforming the new product development in the cosmetic field because of consumer perceivable benefits and optimized sensory attributes. The applications of novel drug delivery systems can be found in many cosmetic products. Nanomaterials are nowadays used in almost all major cosmetic industries. The truth is, there is no magic pill at present that will retard aging. But that is not to say there are not simple lifestyle and dietary adjustments that can make people live longer. A cosmetic product that produces clinically objective effects on the most-reported signs of aging is an attractive option for those unable to avoid extrinsic aging factors but wishing to improve their appearance without resorting to more invasive measures.

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