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The Kinetics of Senescence in Retinal Pigmented Epithelial Cells: a Test for the Telomere Hypothesis of Ageing?

V. Rawes,1 D. Kipling,2 I. R. Kill,3 and R. G. A. Faragher1,4

1Ocular Research Group, Department of Pharmacy, University of Brighton, Brighton BN2 4GJ, UK; fax: +44-1273-679-333; E-mail: rgaf@brighton.ac.uk

2Department of Pathology, College of Medicine, University of Wales, Heath Park, Cardiff CF4 4XN, UK; fax: +44-1222-743-524; E-mail: KiplingD@cardiff.ac.uk

3Department of Biological Sciences, The University, Dundee DD1 4HN, UK; E-mail: i.r.kill@dundee.ac.uk

4To whom correspondence should be addressed.

Submitted July 7, 1997.
Senescence, or replicative failure, has been reported for a wide variety of human cell types but has seldom been characterized in any detail. The senescence of human fibroblast cultures has been shown to be due to a steadily decreasing percentage of cells able to proliferate in standard media. This paper reports the serial subculture of a strain of adult retinal pigmented epithelial (RPE) cells until replicative failure after ~15 population doublings. Measurement of the growth fraction of the RPE cells at each passage using antibodies to the proliferation marker pKi67 demonstrated a rate of decline in the proliferating fraction of 3.66% per population doubling. Similar experiments carried out using a strain of human fibroblasts yielded a decline of approximately 0.88% per population doubling. Thus, individual RPE cells enter senescence significantly faster than control fibroblasts (p < 0.001). At growth arrest the RPE cells retained viability for extended periods but showed elevated endogenous autofluorescence, analogous to observations on post-mitotic human fibroblasts. Taken together these findings suggest that the process of senescence is a common feature of different cell lineages but that the specific rate can differ between them. The significance of these observations for the telomere hypothesis of senescence is discussed.
KEY WORDS: ageing, telomere, retinal pigmented epithelial cell, senescence, macular degeneration.