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Life Extension Magazine June 2013

Youth serum

On the role of thymopoietins in cell proliferation. Immunochemical evidence for new members of the human thymopoietin family.

Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control, as has been shown for lamina-associated polypeptides 2 alpha and beta, which are the rat homologs of human TMPOalpha and TMPObeta, respectively. The recent isolation and characterization of seven mouse TMPO mRNA transcripts named TMPO-alpha, beta, beta’, gamma, epsilon delta and zeta, suggest that more than the three previously reported transcripts, alpha, beta, and gamma forms, may exist in humans. Here we report on the demonstration of putative human TMPOdelta and epsilon by immunoblotting of human cell lines using a newly prepared polyclonal antiserum against the common N-terminal region of TMPO. Furthermore, we prepared the first truly TMPO-beta-specific, affinity-purified polyclonal antiserum, using a part of the human analog of the beta-specific domain of mouse TMPO 220-259 for immunization. We showed that human TMPObeta is highly expressed in all cancerous cells tested, while hardly any cross-reactivities with other proteins could be detected. In contrast to the high expression of human TMPObeta in the cancer-derived neuroblastoma cell lines SK-N-MC and SMS-KAN, we found very low expression of human TMPObeta in low-proliferative nerve tissue. These data led us to the assumption that expression of TMPObeta may correlate with the occurrence of cancer, and therefore may serve as a new tumor marker, or even as a new target for cancer therapy.

Biol Chem. 1999 Jun;380(6):653-60

Molecular biology of keratinocyte differentiation.

Epidermal keratinocytes (skin cells) are highly specialized epithelial cells designed to perform a very specific function, separation of the organism from its environment. To accomplish this the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments. The intermediate filaments are assembled from keratin monomers and the cornified envelope is assembled from a protein called involucrin and several other proteins. Expression of involucrin and the keratins genes are regulated as a function of the stage of keratinocyte differentiation and by various external agents such as calcium and vitamin A. To study the function of these structures and the regulation of precursor production we have cloned cDNA and genomic clones encoding involucrin and four of the keratin polypeptides. Retinoids profoundly alter the differentiation pattern of human epidermal keratinocytes, but the underlying biochemical basis of this change is not known. In this report we describe retinoid-promoted changes in keratin gene expression that may, in part, be responsible for the alteration in cellular phenotype in the presence of the vitamin. We also describe the novel structure of the human 40 kD keratin, a member of the keratin family that is retinoid responsive and is likely to be important during epidermal development. Finally, we describe the structure of the envelope precursor protein, involucrin, as determined from its DNA sequence and speculate on its role in cornified envelope formation.

Environ Health Perspect. 1989 Mar;80:109-16

Aging of human epidermis: reversal of aging changes correlates with reversal of keratinocyte fas expression and apoptosis.

The goal of this study was to determine the role of Fas-mediated apoptosis in human epidermal aging. Epidermal Fas expression and apoptosis are increased in aged human skin. Aging changes of human epidermis, including decreased epidermal thickness and proliferation, are reversed following grafting of human skin to SCID (severe combined immunodeficiency) mice. Skin from aged participants (n = 14; mean 70.7 years), and young participants (n = 14; mean 23.4 years) was grafted to beige SCID mice, and epidermal thickness, proliferation (Ki-67 expression), apoptosis (TUNEL [Tdt-mediated dUTP nick end labeling] reaction below granular layer), and expression of Fas and FasL were determined by histology and immunochemical staining. Aged skin was associated with thinning of the epidermis, decreased epidermal proliferation, a significant increase in apoptosis below the granular layer, and epidermal Fas expression. Engraftment significantly reversed these aging changes, including apoptosis, and Fas expression. Correlation of reversal of aging changes, with decreased epidermal Fas expression and apoptosis, supports a role for Fas-mediated apoptosis in aging of human epidermis

J Gerontol A Biol Sci Med Sci. 2004 May;59(5):411-5

Influence of carrageenan on the rheology and skin permeation of microemulsion formulations.

Three different microemulsions (A-C) and one semisolid preparation D were investigated in terms of viscoelastic properties and skin permeation of the model compound sodium fluorescein. The influence of the polysaccharide carrageenan on these parameters was investigated. Carrageenan is frequently used as food additive and has very interesting properties like good adhesiveness on skin which can be a benefit for topical application. The viscoelastic properties of the preparations (A-D) and of mixtures with carrageenan (A’-D’) were characterized by oscillatory measurements. It was possible to adjust the rheologic properties of the formulations and to increase the sodium fluorescein permeation through porcine skin by mixing them with carrageenan gels. Therefore, the presented formulations as well as mixtures with carrageenan might be promising alternative drug carrier systems for topical pharmaceutical as well as cosmetics.

J Control Release.2004 Mar 5;95(2):257-65

Seaweed vitamins as nutraceuticals.

Seaweeds are a good source of some water- (B(1), B(2), B(12), C) and fat-soluble (β-carotene with vitamin A activity, vitamin E) vitamins. To ensure that the adequate intake of all vitamins is received in the diet, people (especially people on special diet, strict vegetarians, and vegans) can consume foods enriched with vitamins, for example, in the form of functional foods with vitamins as nutraceuticals, extracted from natural sources such as seaweeds. Seaweed vitamins are important not only due to their biochemical functions and antioxidant activity but also due to other health benefits such as decreasing of blood pressure (vitamin C), prevention of cardiovascular diseases (β-carotene), or reducing the risk of cancer (vitamins E and C, carotenoids).

Adv Food Nutr Res. 2011;64:357-69

Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts.

The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

Biochem Biophys Res Commun.2012 Nov 23;428(3):416-21

Topical vitamins, minerals and botanical ingredients as modulators of environmental and chronological skin damage.

Ageing skin is characterized by fine lines, wrinkles, lentigines, dyspigmentation and increased coarseness. Topical preparations alleged to combat these changes abound in the over-the-counter market. Some of the most popular ingredients used in these products are vitamins, minerals and botanical extracts. Proposed mechanisms for antiageing effects on skin range from antioxidant properties to improved collagen synthesis or protection from collagen breakdown. Despite the media attention and consumer popularity that these ingredients have generated, there have been few scientific studies to support these claims. In this report, we review recent published studies on the most common of these ingredients for the topical photoprotection and the treatment of ageing skin.

Br J Dermatol.2003 Oct;149(4):681-91

Antioxidant activity of proteins and peptides.

Proteins can inhibit lipid oxidation by biologically designed mechanisms (e.g. antioxidant enzymes and iron-binding proteins) or by nonspecific mechanisms. Both of these types of antioxidative proteins contribute to the endogenous antioxidant capacity of foods. Proteins also have excellent potential as antioxidant additives in foods because they can inhibit lipid oxidation through multiple pathways including inactivation of reactive oxygen species, scavenging free radicals, chelation of prooxidative transition metals, reduction of hydroperoxides, and alteration of the physical properties of food systems. A protein’s overall antioxidant activity can be increased by disruption of its tertiary structure to increase the solvent accessibility of amino acid residues that can scavenge free radicals and chelate prooxidative metals. The production of peptides through hydrolytic reactions seems to be the most promising technique to form proteinaceous antioxidants since peptides have substantially higher antioxidant activity than intact proteins. While proteins and peptides have excellent potential as food antioxidants, issues such as allergenicity and bitter off-flavors as well as their ability to alter food texture and color need to be addressed.

Crit Rev Food Sci Nutr. 2008 May;48(5):430-41

Thymic involution in aging. Prospects for correction.

The thymus produces several putative thymic hormones: thymosin alpha 1, thymulin, and thymopoietin, which have been reported to circulate and to act on both prothymocytes and mature T cells in the periphery, thus maintaining their commitment to the T cell system. These endocrine influences decline with age and are associated with “thymic menopause” and cellular immune senescence, which contribute to the development of diseases in the aged. Thymus endocrinology is characterized by the action of many hormones and hormone-like substances on the cellular components of the thymus, including thymocytes, thymic epithelial cells, and thymic stromal cells. The intrathymic environment is characterized by a complex network of paracrine, autocrine, and endocrine signals involving both interleukins and thymic peptides, which can be envisioned to operate in a synergistic network to carry the evolving T cell through its stepwise development to a mature T cell. Extrathymic influences regulating the secretory function of thymic epithelial cells and the stepwise evolution of T cells can be ascribed to circulating interleukins, mainly IL1 and IL2, derived from activation and secretion of leukocytes in the periphery. These interleukins act in a synergistic fashion at all levels of T cell development by the induction of high-affinity IL2 receptors and the resultant IL2-dependent proliferative responses. To determine whether exogenous administration of interleukins would induce T lymphocyte development in aged mice, we chemically thymectomized aged mice with a steroid hormone and treated them with mixed interleukins or thymic hormones such as thymosin. We found that mixed interleukins, but not thymosin, restored thymic weight and cellularity and enhanced thymocyte responses to interleukins and mitogen. Thymosin potentiated the effect.

Ann N Y Acad Sci. 1992 Dec 26;673:231-9

Proteolytic-based method for the identification of human growth hormone.

Human growth hormone (HGH) is a relatively small protein consisting of 191 amino acids and has an average mass of 22,125 amu. The forensic analysis of proteins such as HGH must meet the analytical sufficiency requirements for the laboratory and consists of a binary approach. A suspected sample is analyzed as the whole protein for retention time and mass determination using high performance liquid chromatography equipped with a photodiode array and liquid chromatography mass spectrometry. Further fragmentation of the protein using a proteolytic enzyme adds another dimension to the specificity of the analysis. Porcine trypsin digests proteins in a very predictable manner and yields peptide fragments of the original protein that can be used as a means for fingerprinting the larger biomolecule. In silico, or theoretical, digestion of HGH by trypsin yields 21 peptides ranging in size from 1 to 23 amino acids in length. The larger fragments containing higher numbers of amino acids give more specificity to identifying a protein based on a fragment produced by the digestion of trypsin. Herein, the analysis of HGH using a proteolytic approach is presented that meets the Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) recommendations for the identification of unknown substances.

J Forensic Sci. 2009 Jan;54(1):122-7