If ageing is genetically programmed, as extensive data suggest it is at least in part, then ageing at the cellular level may be considered, by definition, a form of differentiation. The term "dysdifferentiation" has also been proposed to denote "relaxation" of gene expression, perhaps due to age-associated loss of DNA methylation. Within tissues or cultured cell populations, ageing may result from an increase in the proportion of more differentiated cells at the expense of relatively non -differentiated ones that perhaps have a greater proliferative potential and /or more functional behavioural responses, or may result from a relatively uniform shift in behaviour for all cells.
Barrandon and Green have shown that with increasing donor age, individual keratinocytes, on average, have a markedly decreased proliferative potential as manifested by generation of fewer and smaller colonies in vitro. Extensive studies by Bayreuther and coworkers have defined a panel of six surface antigens for dermal fibroblasts that putatively distinguish between cells in different states of differentiation. Using immunofluorescent staining techniques they have correlated the presence of specific markers with young vs old donor age, early vs late passage level and high vs low proliferative potential. The very recent keratinocyte and fibroblast studies discussed above suggest that differentiation-like age-associated changes occur at the level of gene expression (mRNA level), as well as at the levels of proliferative response and protein expression.
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