elastin and Aging--Premature

Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

Topics: Administration, Topical; Aging, Premature; Cells, Cultured; Elastin; Gene Expression Regulation; Glucuronosyltransferase; Humans; Hyaluronan Synthases; Hyaluronic Acid; Keratinocytes; Organ Culture Techniques; Skin; Skin Aging; Vitamin A

Progressive proteolytic degradation of cutaneous elastic fibers, that cannot be adequately replaced or repaired by adult dermal fibroblasts, constitutes a major feature of aging skin. Our present investigations, employing monolayer cultures of human dermal fibroblasts and organ cultures of skin biopsies, were aimed at testing whether the hydrophilic tannic acid (TA) and lipophilic ellagic acid (EA) would protect dermal elastin from exogenous and endogenous enzymatic degradation. Results from both culture systems indicated that dermal fibroblasts, maintained with TA or EA, deposit significantly more elastic fibers than untreated control cultures despite the fact that neither polyphenol enhanced transcription of elastin mRNA or cellular proliferation. Results of a pulse and chase experiment showed that pretreatment with both polyphenols enhanced biostability of tropoelastin and newly deposited elastin. Results of in vitro assays indicated that both polyphenols bound to purified elastin and significantly decreased its proteolytic degradation by elastolytic enzymes belonging to the serine proteinase, cysteine proteinase, and metallo-proteinase families. Importantly, both polyphenols also synergistically enhanced elastogenesis induced by selected elastogenic compounds in cultures of dermal fibroblasts. We propose that EA and TA may be useful for preventing proteolytic degradation of existing dermal elastic fibers and for enhancing more efficient elastogenesis in aged skin.

Topics: Adolescent; Adult; Aging, Premature; Child; Child, Preschool; Elastic Tissue; Elastin; Ellagic Acid; Female; Fibroblasts; Humans; Middle Aged; RNA, Messenger; Skin; Tannins; Tropoelastin

Two sisters with inherited generalized cutis laxa and a young man with possible acquired cutis laxa are presented.

Topics: Adolescent; Adult; Aging, Premature; Consanguinity; Cutis Laxa; Elastin; Female; Fibroblasts; Humans; Male; Pedigree