The relationship between in vitro cellular aging and in vivo human age.

Abstract

Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging." However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflect human cellular aging in vivo. Studies were therefore undertaken to determine if significant differences would be observed in the in vitro lifespans of skin fibroblast cultures from old and young normal, nonhospitalized volunteers and to examine if parameters that change with in vitro "aging" are altered as a function of age in The limited lifespan of cultured human diploid fibroblasts in vitro has led to their extensive utilization as a model system for studying human cellular aging (1-3). These human fetal lung fibroblasts in their last passages are often referred to as representing "aged" cell populations (4-6). Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging" (4-6). However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflects human cellular aging in vivo (7-9). One of the most frequently cited justifications for the use of cultured fibroblasts for studying human cellular aging is the reported decline in the cumulative number of cell population replications in vitro and earlier onset of cell culture senescence with the increasing age of the cell culture donor (10, 11). Recently, however, the statistical analysis and population selection used in these studies have been questioned (7,8).The studies to be described in this report had two major goals: (i) to determine if statistically significant differences would be observed in the onset of cell culture senescence and the cumulative replication capacity of fibroblast cultures derived from old and young normal, nonhospitalized human volunteers; and (ii) to examine if parameters that change with increased in vitro "aging" are altered as a function of in vivo age. This latter asAbbreviation: CPD, cell population doublings. * Present address: Tokyo Metropolitan Institute of Gerontology, Sakaecho, Itabashiku, Tokyo-173, Japan. pect was approached by comparing cell population replication rate, percent replicating cells, cell number at confluency, cell volume, and cellular macromolecular contents in cell cultures from old and young human donors (aging in vivo) as well as in early and late passage cell cultures ("aging" in vitro). MATERIALS AND METHODSCell Culture. After informed consent had been obtained, skin punch biopsies, 2 mm in diameter, were performed on the inner aspect of the upper arm of nonhospitalized male volunteers. The subjects were interviewed prior to biopsy, and those individuals with a history of diabetes or who were receiving steroid medication were not included in this study. The skin specimen was divided into four equal explants and two each were placed between coverglass sandwiches in Leighton tubes. ...

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

“…A cross-sectional study by Martin et al (1970) revealed such an effect, with an average reduction in lifespan of 0.2 population doublings per year of age, although there was considerable variability within each age group. A similar difference was also reported in a comparison of cultures from young (21-36 years) and old (63-92 years) donors (Schneider and Mitsui 1976). A further correlation between in vitro and in vivo ageing was found by Smith et al (1978) in studies on age-related changes in colony size distributions among individual fibroblasts.…”

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

“…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.…”

“…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.…”

Vejez y cáncer de mama, el desafío del siglo 21

“…Si mutaciones somáticas impiden que la célula senescente salga del ciclo celular, las divisiones celulares mantenidas, asociadas a una disfunción del telómero, ocasionarían gran inestabilidad genómica conocida como "crisis del telómero" 17 . Por otro lado, este fenómeno de senescencia celular aumenta la resistencia a la apoptosis 16 otro lado, la declinación en la respuesta inmune observada con el envejecimiento favorecería el desarrollo de neoplasias debido a la tolerancia inmune [18][19][20] . Mecanismos epigenéticos, como la hipermetilación de islas CpG (citosina-guanina) cercana a zonas promotoras, han mostrado ser un mecanismo común de silenciamiento de genes supresores de tumores progresivo con la edad 21 .…”