Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Inflammation and the resulting accumulation of reactive oxygen species (ROS) play an important role in the intrinsic and photoaging of human skin in vivo. Environmental insults such as ultraviolet (UV) rays from sun, cigarette smoke exposure and pollutants, and the natural process of aging contribute to the generation of free radicals and ROS that stimulate the inflammatory process in the skin. UV irradiation initiates and activates a complex cascade of biochemical reactions in human skin. In short, UV causes depletion of cellular antioxidants and antioxidant enzymes (SOD, catalase), initiates DNA damage leading to the formation of thymidine dimmers, activates the neuroendocrine system leading to immunosuppression and release of neuroendocrine mediators, and causes increased synthesis and release of pro-inflammatory mediators from a variety of skin cells. The pro-inflammatory mediators increase the permeability of capillaries leading to infiltration and activation of neutrophils and other phagocytic cells into the skin. The net result of all these effects is inflammation and free radical generation (both reactive oxygen and nitrogen species). Furthermore, elastsases and other proteases (cathepsin G) released from neutrophils cause further inflammation, and activation of matrix metalloproteases. The inflammation further activates the transcription of various matrixes degrading metalloproteases, leading to abnormal matrix degradation and accumulation of non-functional matrix components. In addition, the inflammation and ROS cause oxidative damage to cellular proteins, lipids and carbohydrates, which accumulates in the dermal and epidermal compartments, contributing to the aetiology of photoaging. Strategies to prevent photodamage caused by this cascade of reactions initiated by UV include: prevention of UV penetration into skin by physical and chemical sunscreens, prevention/reduction of inflammation using anti-inflammatory compounds (e.g. cyclooxygenase inhibitors, inhibitors of cytokine generation); scavenging and quenching of ROS by antioxidants; inhibition of neutrophil elastase activity to prevent extracellular matrix damage and activation of matrix metalloproteases (MMPs), and inhibition of MMP expression (e.g. by retinoids) and activity (e.g. by natural and synthetic inhibitors).

Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation – a review

UV skin exposure induces extensive generation of reactive oxygen species (ROS). These can react with DNA, proteins, fatty acids and saccharides causing oxidative damage. Such injuries result in a number of harmful effects: disturbed cell metabolism, morphological and ultrastructural changes, attack on the regulation pathways and, alterations in the differentiation, proliferation and apoptosis of skin cells. These processes can lead to photoaging and skin cancer development. One approach to protecting human skin against the harmful effects of UV irradiation is to use antioxidants as photoprotectives. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. In this review, we strive to summarize the findings of studies performed to date, regarding the photoprotective effects of plant phenolics on the skin damage induced by UV radiation.

/pdf/natural-phenolics-in-the-prevention-of-uv-induced-skin-5dfnsvbalu.pdf

Natural phenolics in the prevention of UV-induced skin damage. A review.

http://www.pnei-it.com/1/upload/bioactive_compounds_from_natural_resources_against_skin_aging.pdf

Bioactive compounds from natural resources against skin aging.

In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting.

https://www.mdpi.com/1660-3397/14/3/42/pdf

Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications.

Background Previously, we have demonstrated that fibroblast-derived elastase plays an essential role in the increased three-dimensional tortuosity of elastic fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This decrease in skin elasticity is closely associated with the formation of wrinkles induced by UV exposure.



Objective  To further clarify the role of elastase in the formation of wrinkles induced by UV exposure, we assessed the effects of an extract of Zingiber officinale (L.) Rose (which inhibits fibroblast-derived elastase) on the wrinkle formation induced by chronic UV-B irradiation.



Results  Topical application of an extract of Zingiber officinale (L.) Rose to rat or hairless mouse skin significantly inhibited the wrinkle formation induced by chronic UV-B irradiation at a suberythemal dose, which was accompanied by a significant prevention of the decrease in skin elasticity in both types of animal skin. In the rat hind limb skin, consistent with the inhibition of reduced skin elasticity, wrinkle prevention occurred concomitantly with a significant decrease in the curling and three-dimensional tortuosity of dermal elastic fibers.



Conclusion  Our results indicate that herbal extracts with an ability to inhibit fibroblast-derived elastase may prove to be effective as antiwrinkling agents, confirming the important role of elastase in UV-B-induced wrinkle formation.

Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting herbal extract: implication for the mechanism underlying elastase-associated wrinkles

Selective Inhibition of Skin Fibroblast Elastase Elicits a Concentration-Dependent Prevention of Ultraviolet B-Induced Wrinkle Formation

Comparison of age-related changes in facial wrinkles and sagging in the skin of Japanese, Chinese and Thai women

Background Ultrasonography has been used as a non-invasive approach to measure skin thickness. To date there have been no studies on diurnal variations in skin thickness.



Objectives To evaluate diurnal variations in skin thickness and to compare these with corresponding echogenicity and skin elasticity.



Methods Measurements by ultrasonography B-mode and by Cutometer SEM 575 were carried out in the morning and in the afternoon on 20 men and 20 women (mean age 30 years) on three areas of the face (forehead, corner of the eye and cheek), the forearm and the upper arm, and the flank, thigh and calf.



Results From the morning to the afternoon, the skin thickness in both sexes significantly decreased on three areas of the face, the forearm and the upper arm, but significantly increased on the thigh and calf. In parallel, the echogenicity significantly increased from the morning to the afternoon on the three areas of the face, the forearm and the upper arm, but decreased significantly on the thigh and calf. Measurements of mechanical properties at four sites demonstrated that from the morning to the afternoon, the major parameters of skin elasticity Ue* and Uf* increased significantly in both sexes on two areas of the face and slightly on the forearm, but decreased significantly on the calf.



Conclusions The diurnal profiles of skin thickness and skin elasticity in the upper half of the body are the reverse of those in the lower half of the body. These findings suggest that shifts of dermal fluid from the face to the leg by gravity during the day cause the diurnal variation in skin thickness.

Dermal fluid translocation is an important determinant of the diurnal variation in human skin thickness.

We compared age-related changes in wrinkles in eight areas of facial skin (forehead, glabella, upper eyelid, corner of the eye, lower eyelid, nasolabial groove, cheek, and corner of the mouth) and sagging in the subzygomatic area of Caucasian females and of Japanese females. The subjects studied included 85 healthy Caucasian females (ages 20-69 years) living in Cincinnati in the U.S. and 70 Japanese females (ages 20-69 years) living in Tokyo. Photos of the face in frontal and in oblique 45 degrees views were analyzed. Wrinkles in the face and sagging in the subzygomatic area were graded on Japanese photoscales, respectively, by the same experienced observer. The wrinkle score increased with age in all eight areas of the face examined in Caucasian females as well as in Japanese females. In the group aged 20-29 years, the wrinkle score in each area was significantly higher in Caucasian females than in Japanese females. The wrinkle scores in the forehead, glabella, upper eyelid, and corner of the eye were similar at advanced ages between the two groups, while the wrinkle scores in lower areas of the face (lower eyelid, nasolabial groove, cheek, and corner of the mouth) were markedly higher in Caucasian females than in Japanese females in each age group, and reached an upper limit at advanced ages in Caucasian females. The sagging score also increased with age in Caucasian females as well as in Japanese females. The sagging score was significantly higher in Caucasian females than in Japanese females in the groups aged 40 years or more. These results suggest more marked wrinkle formation in all areas of the face in younger age groups of Caucasian females living in North America than in Japanese females living in Tokyo. In particular, Caucasian females showed marked age-related wrinkle formation in the lower areas of the face, probably due to sagging in the subzygomatic area, which suggests a higher susceptibility to sagging in the subzygomatic area of Caucasian females.

Kazue Tsukahara

Papers

Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting herbal extract: implication for the mechanism underlying elastase-associated wrinkles

Selective Inhibition of Skin Fibroblast Elastase Elicits a Concentration-Dependent Prevention of Ultraviolet B-Induced Wrinkle Formation

Comparison of age-related changes in facial wrinkles and sagging in the skin of Japanese, Chinese and Thai women

Dermal fluid translocation is an important determinant of the diurnal variation in human skin thickness.

Comparison of age-related changes in wrinkling and sagging of the skin in Caucasian females and in Japanese females