In vitro senescence of Syrian hamster mesenchymal cells of fetal to aged adult origin. Inverse relationship between in vivo donor age and in vitro proliferative capacity

Bruce, Sarah A.; Deamond, Scott F.; Ts’o, Paul O. P.

doi:10.1016/0047-6374(86)90032-1

Cited by 51 publications

(25 citation statements)

References 28 publications

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“…Of course, these were inbred animals in a constant environment, so presumably some aspects of heterogeneity were reduced. Similar results were found for syrian hamsters (14).…”

Section: Vj Cristofalosupporting

confidence: 79%

Cell culture aging: Insights for cell aging in vivo?

1999

Aging Clin Exp Res

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The bench mark experiments of Hayflick and Moorhead (1) and Hayflick (2) made it clear that normal human cells in culture displaya limited replicative life span.Careful observation of the deterioration in the replicative ability of the cell population, and the morphological and physiological changes that accompanied the proliferative changes led to the interpretation that this phenomenon was reminiscent of cell aging in si tu and, indeed, was human cell aging in culture (3).lnitially, both the observation and the interpretation were controversial. Many in the scientific community, especially gerontologists, resisted the idea that in the presence of adequate nutrition and an otherwise supportive environment, replication could be limited by intrinsic factors, and that the individual cells would undergo senescence in a controlled environment outside the body. However, this finding has been duplicated in many laboratories throughout the world. Furthermore, this general phenomenon of replicative decline during serial subculture was shown to occur in other cell types, such as smooth muscle cells, keratinocytes, endothelial cells and glial cells (reviewed by Cristofalo et al.,4). Gradually through the 1970's, 1980's and 1990's, the validity of the observation of the limited replicated life span of human cells in culture was accepted, although the relationship of the information thus derived to the mechanisms of organismic aging remained controversial.Among the evidence in support of the relevance of senescence in human cell cultures to aging in si tu, the most cited experiments are those showing a small but statistically significant negative correlation between the replicative life span of human skin fibroblast cultures and the age of the donor (2, 5-8).For most investigators, these studies have been the keystone of the arguments for the relevance of cell culture aging to organismic aging.In a recently published study, we reported the replicative life spans of 124 skin fibroblast cultures, ©1999, Editrice Kurtis ranging in age from fetal to 94 years (9). Eight of the donors were fetal-derived, while the rest were volunteers in the Baltimore Longitudinal Study on Aging (BLSA). The donors were certified "healthy" at the time of the biopsy by the criteria used in the BLSA. We found high variability in the replicative potential of different celliines (as others did), but no clear correlation between donor age and fibroblast replicative life span. A similar finding was reported by Goldstein et al. (10) Cristofalo et al. (9) also compared skin fibroblast cell lines from six individuals who provided skin sampies sequentially during their participation in the BLSA, and found no correlation between the age at which the sampie was taken and the replicative life span of the corresponding culture.Unfortunately, these findings, which serve to sharpen our understanding of cell culture senescence, have led some workers to conclude that studies of the aging of cell cultures have no relevance whatsoever to cell aging in the organism. ...

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“…Of course, these were inbred animals in a constant environment, so presumably some aspects of heterogeneity were reduced. Similar results were found for syrian hamsters (14).…”

Section: Vj Cristofalosupporting

confidence: 79%

Cell culture aging: Insights for cell aging in vivo?

1999

Aging Clin Exp Res

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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: 96%

“…The finite replicative lifespan of normal cells in culture is thought to result from multiple environmental and genetic mechanisms (3) and is frequently used as one model of human aging. Supporting the usefulness of this model, several laboratories, by using different types of normal human cells maintained in culture, have presented evidence for a negative correlation between donor age and proliferative lifespan in vitro (4)(5)(6)(7)(8)(9)(10)(11). The colony-forming capacity of individual cells has been reported to decline as a function of donor age (12,13).…”

mentioning

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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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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“…In vitro, fetal and neonatal skin fibroblasts have greater proliferative capacity than adult or aged samples (Bruce et al 1986;Schneider and Mitsui 1976;Martin et al 1970). In addition, fibroblasts in culture lose their proliferative capacity after a number of passages, and when senescence is achieved they are unable to proliferate.…”

Section: Discussionmentioning

confidence: 99%

“…The kinetics of fibroblast growth have been extensively studied in vitro (Bruce et al 1986;Schneider and Mitsui 1976;Martin et al 1970). Studies suggest that proliferation and apoptosis are linked and are developmentally regulated.…”

mentioning

confidence: 99%

Apoptosis and Proliferation of Fibroblasts During Postnatal Skin Development and Scleroderma in the Tight-skin Mouse

Pablos

Carreira

Serrano

et al. 1997

J Histochem Cytochem.

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SUMMARY Tight-skin (Tsk) is a dominant gene mutation that causes a fibrotic skin disease in mice, similar to human scleroderma. Both conditions are characterized by increased numbers of dermal fibroblasts containing high levels of procollagen mRNA. Whether this fibroblast population arises from fibroblast growth or fibroblast transcriptional activation is debated. Proliferation and apoptosis of fibroblasts of normal and Tsk mice were studied in skin sections before, at onset, and in established fibrosis. Tissue sections were immunostained with proliferating cell nuclear antigen (PCNA) as proliferation marker. Apoptosis was investigated by in situ end-labeling of fragmented DNA and nuclear staining with propidium iodide. The expression of the apoptosis inhibitor Bcl-2 was investigated by immunohistochemistry. We demonstrate differences in fibroblast proliferation and apoptosis related to postnatal skin growth and development. Neonatal skin exhibits the highest levels of proliferation and apoptosis in fibroblasts. In contrast, low proliferation and absence of apoptosis characterizes adult fibroblasts. Skin fibroblasts express Bcl-2 only in newborns, and at other ages Bcl-2 was restricted to epithelial cells. Our results also suggest that neither increased fibroblast proliferation nor defective apoptosis accounts for the fibrotic phenotype of Tsk. Therefore, transcriptional activation of extracellular matrix genes appears more relevant in the pathogenesis of Tsk fibrosis. (J Histochem Cytochem 45:711-719, 1997)

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In vitro senescence of Syrian hamster mesenchymal cells of fetal to aged adult origin. Inverse relationship between in vivo donor age and in vitro proliferative capacity

Cited by 51 publications

References 28 publications

Cell culture aging: Insights for cell aging in vivo?

Cell culture aging: Insights for cell aging in vivo?

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

Apoptosis and Proliferation of Fibroblasts During Postnatal Skin Development and Scleroderma in the Tight-skin Mouse

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