Ageing of Clones of Mammalian Cells

Le, Orgel

doi:10.1038/243441a0

Cited by 406 publications

(85 citation statements)

References 18 publications

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“…Among other effects, one could 136 A Terman et al expect a decrease of autophagic degradative capacity due to an increased formation of defective lytic enzymes. Another once-popular hypothesis (called the 'error catastrophe' theory of ageing) posited that cells senesce and die because of too many translational errors [18]. Although attractive, both hypotheses generally failed.…”

Section: Ageing As a Catabolic Insufficiencymentioning

confidence: 99%

Autophagy, organelles and ageing

Terman

Gustafsson

Brunk

2007

The Journal of Pathology

263

210

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As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological 'garbage' ('waste' materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death.

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Section: Ageing As a Catabolic Insufficiencymentioning

confidence: 99%

Autophagy, organelles and ageing

Terman

Gustafsson

Brunk

2007

The Journal of Pathology

263

210

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“…However, the close linkage of the pathways of transcription, translation, replication, and repair of genetic information (Fig. 6) suggests that a more general error theory, which includes the possibility of error feedback at all levels of information transfer, is more plausible (Holliday and Tarrant 1972;Orgel 1973;Brash and Hart 1978;Kirkwood 1980). Evidence to support the hypothesis of a general accumulation of errors in human fibroblasts has been reported (Holliday and Tarrant 1972;Linnet al 1976), but contrary results have also been claimed (Evans 1977;Harley et al 1980).…”

Section: Mechanisms Of Cellular Ageingmentioning

confidence: 93%

“…Some of these implicate quite specific sources of damage, for example macromolecular crosslinkage (Bjorksten 1968), accumulation of toxic metabolic wastes (Sheldrake 1974), racemisation of amino acids (DeLong and Poplin 1977), macromolecular damage caused by free radicals (Harman 1956), or the accumulation of defects in cell membranes (Zs-Nagy 1978; Cremer et al 1981). Others are more general, such as the somatic mutation theory (Szilard 1959;Curtis 1966;Burnet 1974) or the protein error theory (Medvedev 1962;Orgel 1963Orgel , 1973. Each of these mechanisms presupposes that ageing is a process of stochastic cellular deterioration, albeit at a rate which may be genetically controlled through the efficiency of repair mechanisms.…”

Section: Mechanisms Of Cellular Ageingmentioning

confidence: 99%

“…All that is necessary is that there should exist within the population a group of immortal cells which does not decrease in numbers from one subculture to the next (see Orgel 1973). In terms of the commitment theory, for example, a culture can be immortalised by a relatively small change in either the probability of a cell becoming committed, or in the number of cell generations which must elapse before a committed cell ceases to divide (Kirkwood and Holliday 1975).…”

Section: "Immortalisation" Of Transformed Cellsmentioning

confidence: 99%

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

1982

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Summary. Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following'the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro.In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research.

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“…Two main groups of theories which propose (1) that cellular ageing is due to random accumulation of errors in information handling macromolecules [14,15] or (2) that ageing depends on a set of programmed events [16], have provoked zealous efforts for verification. HDF cultures have been employed for such experimental studies [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Senescence in vitro and ionising radiations—the human diploid fibroblast model

Stevenson

Cremer

1981

Mechanisms of Ageing and Development

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SUMMARYThe influence of ionising radiations on ageing is still controversial. Since Hayflick established the concept that diploid cells have finite lifespan in vitro, human diploid fibroblast (HDF) cultures have been recognised as a potent experimental model for cytogerontological investigations. In this study HDF cultures in phase II were exposed to acute irradiation with either X-rays or fast neutrons. The replicative potentials and labelling indices with [3H]thymidine were measured post irradiation until the cultures ceased growth in phase III. Cell mortality was measured by cloning. The apparent loss in replicative potential of irradiated mass cultures was wholly attributable to the loss of viable clonogenic cells. The current concept of precocious clonal senescence in vitro as a late effect of irradiation in clonogenic survivors is not supported by the present experiments. Instead, our results suggest that exposure to a single dose of ionising radiations either causes total replicative incapacitation (killing) of HDF cells and their progeny early after irradiation or leaves their replicative potentials unperturbed.

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Ageing of Clones of Mammalian Cells

Cited by 406 publications

References 18 publications

Autophagy, organelles and ageing

Autophagy, organelles and ageing

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

Senescence in vitro and ionising radiations—the human diploid fibroblast model

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