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For much of the 20th century, the accumulation of a considerable amount of information about the processes of aging did not reveal the underlying mechanisms. Toward the end of that century, the biological basis for aging became very much clearer. It became apparent that the best strategy for animals' survival was to develop to an adult, but not to invest(More)
there is one event in the whole evolutionary sequence at which my own mind lets my awe still overcome my instinct to analyse, and where I might concede that there may be a difficulty in seeing a Darwinian gradualism hold sway throughout almost all, it is this event—the initiation of meiosis. T HE origins of meiosis in early eukaryotic history have never(More)
We have examined the effects of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) on the growth, morphology, and lifespan of cultured human diploid fibroblasts. With human foreskin cells, HFF-1, and fetal lung cells, MRC-5, we have shown that carnosine at high concentrations (20-50 mM) in standard medium retards senescence and(More)
  • R Holliday
  • 1989
Calorie restriction results in an increased lifespan and reduced fecundity of rodents. In a natural environment the availability of food will vary greatly. It is suggested that Darwinian fitness will be increased if animals cease breeding during periods of food deprivation and invest saved resources in maintenance of the adult body, or soma. This would(More)
We have confirmed and extended previous results on the beneficial effects of L-carnosine on growth, morphology, and longevity of cultured human fibroblasts, strains MRC-5 and HFF-1. We have shown that late-passage HFF-1 cells retain a juvenile appearance in medium containing 50 mM carnosine, and revert to a senescent phenotype when carnosine is removed.(More)
5-Methylcytosine (5mC) in DNA is produced by post-synthetic modification of cytosine residues, and it occurs primarily in CpG doublets in the mammalian genome. 5mC is a mutable site, because it can undergo spontaneous deamination to thymine. There is a repair mechanism which specifically recognises G.T mispairs, and replaces thymine with cytosine. However,(More)
In the first half of the twentieth century, developmental biology and genetics were separate disciplines. The word epigenetics was coined by Waddington to link the two fields. Epigenetics could be broadly defined as the sum of all those mechanisms necessary for the unfolding of the genetic programme for development. Several decades later specific mechanisms(More)
The probability of a mouse cell becoming fully transformed in vivo or in vitro is enormously greater than that of a human cell. The number of events in tumour progression is similar in rodent and human cells, and it is unlikely that the difference in neoplastic transformation frequency can be explained on the basis of gene mutation in oncogenes and tumour(More)