Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts

Bruce, Sarah A.; Deamond, Scott F.

doi:10.1016/0531-5565(91)90058-t

Cited by 58 publications

(26 citation statements)

References 14 publications

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“…A similar comparison of groups in our study failed to reveal any significant differences (ANOVA, P ϭ 0.34). Several studies of rodent skin fibroblasts appear to support the existence of a small, though significant, inverse correlation between donor age and replicative lifespan (9,40,41). It has also been observed that treatment of hamster skin fibroblasts with growth promoters can extend the proliferative life of cultures established from young organisms but has negligible effects on cultures established from older donors (42).…”

Section: Discussionmentioning

confidence: 97%

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Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation

Cristofalo

Allen

Pignolo

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

504

265

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Normal human diploid fibroblasts have a finite replicative lifespan in vitro, which has been postulated to be a cellular manifestation of aging in vivo. Several studies have shown an inverse relationship between donor age and fibroblast culture replicative lifespan; however, in all cases, the correlation was weak, and, with few exceptions, the health status of the donors was unknown. We have determined the

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Section: Discussionmentioning

confidence: 97%

“…However, even in rodents the relationship between donor age and proliferative potential is not entirely clear. For example, an examination of hamster skin fibroblast cultures established from the same donors at different ages reveals no age-associated changes in proliferative potential in animals older than 12 mo (41).…”

Section: Discussionmentioning

confidence: 99%

Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation

Cristofalo

Allen

Pignolo

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

504

265

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“…With increasing age, there is a reduction in fibroblast proliferation and life span, an increase in their apoptosis, and a diminished rate of dermal wound healing (59,60). Fibroblasts play a leading role in wound healing, particularly in the skin.…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Alikhani

Boyd

et al. 2005

Journal of Biological Chemistry

188

121

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Both aging and diabetes are characterized by the formation of advanced glycation end products (AGEs). Both exhibit other similarities including deficits in wound healing that are associated with higher rates of fibroblast apoptosis. In order to investigate a potential mechanism for enhanced fibroblast apoptosis in diabetes and aged individuals, experiments were carried out to determine whether the predominant advanced glycation end product in skin, N-⑀-(carboxymethyl) lysine (CML)-collagen, could induce fibroblast apoptosis. In vivo experiments established that CML-collagen but not unmodified collagen induced fibroblast apoptosis and that apoptosis was dependent upon caspase-3, -8, and -9 activity. In vitro experiments demonstrated that CMLcollagen but not control collagen induced a time-and dose-dependent increase in fibroblast apoptosis. By use of blocking antibodies, apoptosis was shown to be mediated through receptor for AGE signaling. AGE-induced apoptosis was largely dependent on the effector caspase, caspase-3, which was activated through both cytoplasmic (caspase-8-dependent) and mitochondrial (caspase-9) pathways. CML-collagen had a global effect of enhancing mRNA levels of pro-apoptotic genes that included several classes of molecules including ligands, receptors, adaptor molecules, mitochondrial proteins, and others. However, the pattern of expression was not identical to the pattern of apoptotic genes induced by tumor necrosis factor ␣.

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“…Martin et al 54 reported that fibroblasts obtained from old pigs showed increased synthesis of fibronectin and collagen III. In a study on hamsters, Bruce and Deamond 55 concluded that age is related to the proliferative ability or the function of fibroblasts, as well as to the production and organization of the extracellular matrix, which was progressively reduced in older animals. Mays et al 56 reported that collagen synthesis is activated in old rats but that collagen degradation is also increased.…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on abdominal wall healing in rats

et al. 2005

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Purpose:The aim of this study was to assess abdominal wall healing in old and young adult rats. Methods: On average, young animals were 110 days old and old animals were 762 days old. A 4.0 cm median laparotomy was performed under anesthesia, followed by laparorrhaphy on two synthesis planes, i.e. peritoneum-muscle-aponeurosis and skin, using continuous 5.0 nylon sutures. The animals were evaluated on the 3 rd , 7 th , 14 th and 21 st postoperative days. The resistance of the two planes was studied separately and a histopathologic analysis was performed on sections stained with hematoxylineosin and Sirius Red. Immunohistochemical analysis was also carried out using PCNA, LCA and CD34. Results: The skin scars gained resistance in a similar manner at the initial time points, but those of young rats were more resistant on the 21 st day (p=0.0029). Total and type III collagen content was similar in the two groups and type I collagen content was higher in young animals on the 14 th day. Inflammatory cell infiltration was more marked in the skin wounds of young animals on the 3 rd day (p=0.0190). Reepithelialization was similar and angiogenesis was more intense in the skin wounds of young animals on the 14 th day (p=0.0062). The peritoneum-muscle-aponeurosis wounds gained similar resistance during the early phases, but were more resistant on the 14 th day (p=0.0005) and on the 21 st day (p=0.0023) in old rats Collagen concentration was higher in the wounds of old animals on the 3 rd day (p=0.0112) and in the wounds of young animals on the 21 st day (p=0.0348). The inflammatory reaction was more intense in the wounds of old animals on the 3 rd day (p=0.0060) and angiogenesis was more intense on the 14 th day (0.0432). Conclusion: Although there are some differences in the healing course between young and old animals, age, of itself, does not impair the healing of abdominal wall wounds in rats. Key words: Wound healing. Aging. Abdominal wall. Rats. RESUMOObjetivo: Estudar a cicatrização da parede abdominal em ratos adultos jovens e velhos. Métodos: Os ratos adultos jovens tinham em média 110 dias de idade e os velhos 762 dias. Uma laparotomia mediana de 4,0 cm foi feita sob anestesia, seguida de laparorrafia com 2 planos de síntese, isto é, peritônio-músculo-aponevrose e pele, com síntese contínua de fio de náilon 5.0. Os animais foram avaliados com 3, 7, 14 e 21 dias de pós-operatório. A resistência dos dois planos foi avaliada separadamente e a análise histológica feita em cortes preparados pela Hematoxilina-eosina e Sirius red. Análise imunohistoquímica foi realizada empregando PCNA, LCA and CD34. Resultados: A cicatriz da pele ganhou resistência de modo similar nos tempos iniciais, mas as dos animais jovens foram mais resistentes no 21º dia (p=0.0029). A densidade de colágeno total e tipo III foi similar nos dois grupos, porém o colágeno tipo I mostrou-se mais denso nas cicatrizes dos animais jovens no 14.º dia. O infiltrado de células inflamatórias foi maior nas cicatrizes dos animais jovens no 3.º dia (p=...

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Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts

Cited by 58 publications

References 14 publications

Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation

Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Effects of aging on abdominal wall healing in rats

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