The purpose of this paper is to review and to illustrate some of the themes underlying recent research on the aging of connective tissues. The systematic variation with age of the relative rates of biosynthesis (and of degradation) of the macromolecules of the intercellular matrix (collagens, elastin, proteoglycans and structural glycoproteins) is interpreted as the result of an "age program" of matrix synthesis by differentiated mesenchymal cells. This relative rates of synthesis of a well-defined set of matrix macromolecules can be used in its turn to define the state of differentiation (and of aging) of mesenchymal cells. This relative rate of synthesis of a well-defined set of matrix macromole-followed by its degradation through the elastases. The increasing frequency of some diseases with age ("aging diseases" of connective tissues, athero-/arteriosclerosis, diabetes, osteoarticular diseases, etc.) is probably related to this changing composition of the intercellular matrix. Cell-matrix interaction does depend on the secretion of a specific matrix which in its turn influences cell behaviour. With changing matrix composition (changing cell environment) cell behaviour will also change. This informational feedback mechanism may be of great importance in the aging of connective tissues and also in the increasing frequency of some pathologies with age.

Adolescent↗

PubMedDate not supplied

Elastic fibers in normal human skin. Variations with age: a morphometric analysis.

A quantitative study of dermal elastic fibers was carried out by computerized digital image analysis. Sections of skin biopsies taken from the upper inner arm of 33 healthy women and 38 healthy men were stained by a selective procedure for elastic fibers. The Leitz texture analysis system (Leitz-Tas) and mathematical morphology were used for the evaluation of the data. Distinct programs were used for the vertical superficial elastic fibers and for the mature elastic fibers of the reticular dermis. For elastic fibers of the superficial dermis there was no significant variation with age or sex for total area occupied by the fibers or for the total number of fibers per unit skin area or total fiber length. The distribution of the relative fiber number as a function of their length showed that about 80% of the fibers had a length of 0-20 microm, with no detectable age- or sex-dependent variation. The distribution of fiber number frequency as a function of fiber diameter did not show any significant variation with sex or age, either. The relative area of mature elastic fibers increased significantly with age after the sixth decade of life. The total number (Nt) of these fibers did not show however any significant variation with age or sex: Nt per mm(2) of skin surface was 3220+/-660 (S.D.). We found for all age groups a significant increase of total fiber length by comparing persons between 20 and 30 years with those above 60 years. There was, however, no significant variations according to age or sex for the frequency distribution of mature elastic fiber length and diameter. As a significant decrease with age of the dermal thickness was also found in males and females, the loss of elastic fibers with age is mainly due to a loss of skin thickness (skin volume) with age. This loss is about 30% at 50 years and nearly 50% at 80 years. Loss of skin elasticity with age can be due to loss of cells (fibroblasts), to a decrease of their biosynthetic activity and to qualitative modifications of extracellular matrix macromolecules.

Journal Article↗

PubMedDate not supplied

Morphometric analysis of dermal collagen fibers in normal human skin as a function of age.

A quantitative study of dermal collagen as a function of age was carried out by computerized digital image analysis. Fast Green-Syrius Red stained sections were obtained of skin biopsies taken from the upper inner arm of 33 healthy women and 38 healthy men. The Leitz texture Analysis System (Leitz-TAS) and mathematical morphology (Serra, 1982) were used for the evaluation of the data. Collagen was studied in the superficial dermis and also in the reticular dermis using the same program. There were significant correlations, firstly between the percentage of collagen measured by the morphometric method and the concentration of collagen analysed biochemically (microg/mm(2) of tissue section) (r = 0.79, p < 0.001) and secondly between the decreased concentration of collagen and age (r = 0.58, p < 0.05). The morphometrical measurements have shown that the relative percentage of collagen bundles (surface of collagen fibers as a function of the dermal area analyzed) was 93.35% in the superficial dermis and 89.2% in the reticular dermis. Although this value is higher than the chemically determined ratio of collagen to other proteins (over 70%), this may be due to the relatively uniform distribution pattern of (type I and III) collagen through the dermis covering most other components of the skin. As the collagen fiber density per unit dermal surface did not change with age, the decrease in collagen content of the skin may be ascribed to the loss of about 6% of dermal mass per decade (Branchet, 1990), although large individual variations exist. The histogram of the diameter distribution of collagen fiber bundles of the reticular dermis showed thinner diameters in persons between 20 and 40 years of age than in older persons. The histogram of the distribution of interfiber spaces did not show any variation with age in the superficial dermis, while in the reticular dermis there was a predominance of smaller interspaces in persons older than 50 years.

Journal Article↗

PubMedDate not supplied

Stimulation of cell proliferation by hyaluronidase during in vitro aging of human skin fibroblasts.

The effect of the degradation of extracellular hyaluronan on the proliferation of human skin fibroblasts in serial cultures during in vitro aging was investigated. Human skin fibroblasts at different time intervals from 3rd to 36th passages were exposed after plating to bovine testicular hyaluronidase. The enzyme treatment resulted in an increase in cell proliferation (cell number vs. time) as compared to the untreated control fibroblasts. The effect was dose dependent, reversible, and was independent of the type of the glycosidic linkage cleaved in hyaluronan. The increased proliferation was observed at all passages when untreated cells underwent mitosis. The degradation of hyaluronan induced cell proliferation up to the presenescent phase. Depletion of hyaluronan did not induce proliferation of postmitotic fibroblasts. The incorporation of 3H-glucosamine into hyaluronan decreased with increasing cell passages (increase of the number of population doublings). Twenty-fourth passage fibroblasts accumulated about two time less hyaluronan in the medium than ninth passage cultures. Following hyaluronidase treatment, the amount of newly synthesized, labeled hyaluronan increased in the medium. Accordingly, the fibroblasts restored the degraded hyaluronan even in the declining phase of proliferation (phase III according to Hayflick).

Adolescent↗

PubMedDate not supplied

Taenia solium: germinal cell precursors in tapeworms grown in hamster intestine.

BACKGROUND: In a previous study, it was shown that growth of evaginated metacestodes occurs in the germinative tissue of the neck by duplication of somatic stem cells. In these specimens, it was not possible to find the mitotic figures required to demonstrate duplication of germ cell lines. METHODS: Taenia solium strobilae were collected from the intestinal lumen of outbred hamsters infected orally with 10 metacestodes dissected from naturally infected pigs. Animals were anesthetized 1-10 days postinfection, the small intestine excised, submerged in PBS, and cut open longitudinally. Live Taenias were incubated for 6-8 h in medium containing colchicine or 3H-thymidine, washed, and embedded for electron microscopy. For light microscopy and autoradiography, longitudinal sections were cut from whole blocks and mounted on glass slides. A population of large cells without nuclear membranes and containing discrete aggregates of chromatin were observed apposed to myofibrils in the germinative tissue of the neck. These cells were confirmed by electron microscopy as metaphase mitotic figures, with chromosomes attached to a microtubular spindle, embedded in cytoplasm, without a nuclear membrane, and with characteristic centrioles. RESULTS: Only tapeworms in which 3H-thymidine was injected directly into the worm tissue by microsyringe were positive by autoradiography, demonstrating that in contrast to evaginated metacestodes, intestinal worms do not transport thymidine across the tegument. CONCLUSIONS: The results show that differentiating T. solium worms have a subset of stem cells that require passage through a mammalian host to go into mitosis, and that tapeworms grown in an experimental animal do not take up 3H-thymidine in vitro.

Animals↗

PubMedDate not supplied

Age-dependent changes of K-elastin stimulated effector functions of human phagocytic cells: relevance for atherogenesis.

Effector functions of the elastin receptor on human phagocytic cells from young and older individuals were studied. In cells of young healthy subjects the elastin peptides, the agonists of receptor, stimulated both superoxide anion release from PMNs and phagocytosis of coated human red cells by monocytes. Elastin appeared to inhibit the cholesterol synthesis in monocytes, measured by the incorporation of 14C-acetate. In comparison with phagocytic cells of young (< or = 25 +/- 6 years) subjects. PMNs of elderly donors (> or = 75 +/- 10 years) bore a similar number of binding sites for soluble elastin peptides, and the affinity of the elastin receptor was unchanged as shown by Scatchard analysis. The phagocytosis of coated human red cells stimulated by elastin peptides was also similar in the two age groups. However, several differences were found between phagocytic cells of young and elderly donors 1) PMNs of elderly released increased amounts of elastase from both resting and elastin peptide stimulated cells, and 2) monocytes of elderly showed a lack of inhibition of cholesterol synthesis by elastin peptides when maintained in cholesterol-free medium. These changes in effector functions of phagocytic cells from elderly donors might contribute to the age-dependent increase of susceptibility to the development of atherosclerotic lesions.

Adult↗

PubMedDate not supplied

Protection by L-fucose and fucose-rich polysaccharides against ROS-produced cell death in presence of ascorbate.

It was shown previously, that millimolar concentrations of ascorbate have cytotoxic and anti-proliferative effects (Eur. J. Clin. Invest. 32 (2002) 372). With increasing concentrations of ascorbate an increasing number of fibroblasts was detached from the culture dish and shown to be lysed by the effect of ascorbate-induced generation of reactive oxygen species (ROS-s). It also could be shown, that this cytotoxic effect is partly due to the dose-dependent inhibition by ascorbate of fibronectin biosynthesis. Superoxide dismutase (SOD) and catalase were shown to salvage cells from ROS-induced cell-death by preventing the inhibition of fibronectin biosynthesis. We used this model system to test the cyto-protective effect of L-fucose and fucose-rich oligo- and polysaccharides (FROP-s). It appeared that relatively low concentrations of L-fucose and FROP-3 (Biomed. Pharmacother. in press) could efficiently protect fibroblasts from the ascorbate-induced cell-death. These novel pharmacological properties of L-fucose and FROP-3 might well be related to their accelerating effect of wound healing.

Antioxidants↗

PubMedDate not supplied

Pharmacological properties of fucose. Applications in age-related modifications of connective tissues.

Fucose is the only component of glycoconjugates of vertebrates in the L-configuration. It exhibits a number of unique and interesting biological properties reviewed briefly in this article. Its constant end-standing position on glycan chains predisposes fucose to play a key role in cell-cell and cell-matrix interactions, mediated by several receptors such as those recognising the Lewis-type blood group substances, fucose-recognising lectines and the mannose-fucose receptors. Some of the as yet unstudied or less well understood properties of L-fucose were explored in the present study, as its non-enzymatic interaction with amine-groups on macromolecules, its cellular uptake attributed to specific transport mechanisms and its effect on fibroblast cell cultures. We could document the stimulation of cell-proliferation and the inhibition of MMP-expression and activation, both for MMP-2 and MMP-9. These and the other shortly reviewed properties of L-fucose may play an important role in its biological applications and actions.

Aging↗