Age-related decline in the synthesis of glycosaminoglycans by cultured human fibroblasts (WI-38)

Schachtschabel, D.O.; Wever, J.

doi:10.1016/0047-6374(78)90025-8

Cited by 52 publications

(20 citation statements)

References 23 publications

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“…Essentially, these differences were highlighted by an increase in the proportion of heparan sulfate and a decrease in chondroitin sulfate levels in both the cell layer and medium compartment of cultured fibroblasts from donors of increasing age. In this respect, our data support those of Schachtschabel and Wever (1978) and Sluke et al (19811, who also reported an increase in heparan sulfate levels with increase in vitro age of fibroblasts. Indeed, it has been postulated that there may be an inverse correlation between heparan sulfate and cell proliferation (Kraemer and Tobey, 1972;Sluke et al, 1981).…”

Section: Discussionsupporting

confidence: 95%

Proteoglycans synthesized by gingival fibroblasts derived from human donors of different ages

Bartold

Boyd

Page

1986

Journal Cellular Physiology

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The proteoglycans synthesized by fibroblasts derived from human donors of ages ranging from 12 years to 68 years have been studied. In addition, the in vitro proliferation rates of the various cell strains were studied and demonstrated that increasing donor age correlated with a decrease in proliferative activity. The incorporation of [35S]-sulfate into proteoglycans decreased with increasing donor age with cells from the oldest donor demonstrating a 50% reduction compared with cells from the youngest donor. Analysis on Sepharose CL-4B of isolated [35S]-labeled proteoglycans for molecular size distribution revealed few differences between the cell-layer-associated proteoglycans of all cell strains studied. However, analysis of the medium-associated [35S]-labeled proteoglycans demonstrated an increase in the amount of small molecular size proteoglycans with increasing age. More specific analysis of the glycosaminoglycan composition revealed an increase in heparan sulfate from 52% to 73% in the cell-layer-associated proteoglycans of cells from the youngest and oldest donors, respectively. Accompanying this increase was a relative decrease in dermatan and chondroitin sulfate content from 24% to 13% and 25% to 16%, respectively, with increasing donor age. Additionally, the degree of N-sulfation of cell layer heparan sulfate increased with age. Heparan sulfate levels increased in the medium as well with increasing age, with a concomitant decrease in chondroitin sulfate. The quantity of medium-derived dermatan sulfate remained relatively evenly distributed throughout the various ages studied. The various differences noted are considered to reflect the general metabolic changes associated with aging. In particular the increase in heparan sulfate content with age is considered to be related to the decreased proliferative activity of the fibroblasts with increasing age.

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Section: Discussionsupporting

confidence: 95%

Proteoglycans synthesized by gingival fibroblasts derived from human donors of different ages

Bartold

Boyd

Page

1986

Journal Cellular Physiology

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“…This was correlated with decreased sulfotransferase activity, and it was suggested that nonsulfated chondroitins were more prevalent with aging. Schachtschabel and Wever (1978) also noted a greater decline in 35s04= incorporation than in 14C-glucosamine incorporation into extracellular glycosaminogly- Early-passage cells were smaller, appeared more elevated from the substratum, and exhibited some membrane activity.…”

Section: Decreased Extracellular 35s-gag Synthesismentioning

confidence: 93%

“…Second, the phenomenon of in vitro cellular aging represents a model system for investigating the hypothesis that functional change in tissues with aging results from alteration in the synthetic capability of cells which produce extracellular matrix (Cristofalo, 1972;Hayflick, 1977). Decreased synthe-sis of glycosaminoglycans by senescent WI-38 human lung fibroblasts has been reported (Schachtschabel and Wever, 1978).…”

mentioning

confidence: 98%

Glycosaminoglycan synthesis and composition in human fibroblasts during in vitro cellular aging (IMR‐90)

Vogel

Kendall

Sapién

1981

Journal Cellular Physiology

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The synthesis and turnover of sulfate-labeled glycosaminoglycans(35S-GAGs) has been investigated in diploid human embryo fibroblasts during in vitro cellular aging. With progressive subcultivation, there was a decreased incorporation of Na2(35)SO4 into 35S-GAGs released to the medium, but not into those accumulated at the cell surface. The composition of 35S-GAGs found in extracellular medium, cell surface (removable by gentle proteolysis), and intracellular compartments of the culture after 48-hr labeling did not change significantly with progressive subcultivation. Pulse-labeled 35S-GAGs moved from intracellular to surface and extracellular compartments more slowly in late-passage cultures. Addition of 1 mM beta-xyloside to both early- and late-passage cultures produced a ten-fold enhancement of extracellular 35S-GAG production without a concomitant increase in surface-associated 35S-GAG. We interpret the data of this study to mean that secreted and cell-surface glycosaminoglycans represent different pools and that cellular aging has its effect primarily upon the secreted pool of glycosaminoglycans. Late-passage fibroblasts demonstrate marked decreases in proliferation, culture density, fibronectin matrix, and gap-junction formation. Our results suggest that glycosaminoglycan synthesis and composition are not intimately related to these parameters.

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“…This is sustained by the observation that in other human fibroblasts, fibronectin production [24] and the secre tion of GAG [2,3] were also markedly re duced in cells that have been subjected to progressive subcultivation.…”

Section: Discussionmentioning

confidence: 69%

“…This change was mainly related to the GAG fraction released into the me dium. Decreased synthesis of GAG by senes cent WI-38 human lung fibroblasts has also been reported [3], The overall synthesis of collagen and the ratio of a, to ct2 chains of collagen type I produced by rat skin fibro blasts was dramatically affected as cells were serially passaged [4], In bone marrow, stromal cells elaborate and organize ECM molecules [5. 6], which in turn affect the attachment, proliferation and differentiation of progenitor cells [7], As judged by studies performed with long-term marrow cultures, a loss of ECM components correlates with a cessation of active hemo poiesis [8].…”

Section: Introductionmentioning

confidence: 99%

Changes in Collagen Synthesis hy Human Bone Marrow Fibroblasts with Progressive Subcultivation

Fernández

Barahona²,

Martı́nez³

et al. 1989

Pathobiology

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Bone marrow fibroblasts from normal and leukemic patients were used to investigate the relationship between serial subcultivation and changes in collagen synthesis. A regime was established to generate subcultures up to 35 cumulative population doublings (CPDs) in normal cells and to 9 CPDs in leukemic cells. In both types of cells, collagen synthesis decreased as subcultivation progressed. In normal cells, collagen synthesis was reduced to 10% of the original levels at 18 CPDs and in leukemic cells at 8 CPDs. In normal fibroblasts, collagen synthesis was more profoundly affected than overall protein synthesis by subcultivation. In acute lymphoblastic leukemia-derived fibroblasts, the decrease in collagen synthesis paralleled that of total protein.

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Age-related decline in the synthesis of glycosaminoglycans by cultured human fibroblasts (WI-38)

Cited by 52 publications

References 23 publications

Proteoglycans synthesized by gingival fibroblasts derived from human donors of different ages

Proteoglycans synthesized by gingival fibroblasts derived from human donors of different ages

Glycosaminoglycan synthesis and composition in human fibroblasts during in vitro cellular aging (IMR‐90)

Changes in Collagen Synthesis hy Human Bone Marrow Fibroblasts with Progressive Subcultivation

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