Ageing and telomeres: a study into organ- and gender-specific telomere shortening

Abstract

Telomeres, the non-coding sequences at the ends of chromosomes, in the absence of telomerase, progressively shorten with each cell division. Shortening of telomeres can induce cell cycle arrest and apoptosis. The aim of this study was to investigate age- and gender-related changes in telomere length in the rat and to detect possible tissue- specific rates of telomere shortening. Changes with age in telomere lengths were assessed by Southern blotting in the kidney, pancreas, liver, lung and brain of male and female rats. We determined the percentage of telomeres in various molecular size regions rather than measuring the average telomere length. The latter was unable to detect telomere shortening in the tissues. The percentage of short telomeres increased with age in the kidney, liver, pancreas and lung of both males and females, but not in the brain. Males had shorter telomeres than females in all organs analysed except the brain, where the lengths were similar. These findings indicate that telomeres shorten in the rat kidney, liver, pancreas and the lung in an age-dependent manner. These data also provide a novel mechanism for the gender-related differences in lifespan and suggest a tissue-specific regulation of telomere length during development and ageing in the rat.

Loss of Proliferative Capacity and Induction of Senescence in Oxidatively Stressed Human Fibroblasts

“…We have suggested that this shortening is associated with accelerated senescence of renal cells with earlier renal failure and death. It seems unlikely that replicative senescence alone could lead to the degree of shortening observed and therefore telomere shortening consequent upon oxidative damage may be involved (21,22). We have further speculated that telomeres not only function as a measure of the number of cell divisions undergone by telomerase-negative cells but also, by virtue of their GGG content, monitor oxidative damage by the accelerated telomere shortening that results (23).…”

“…Male rats most frequently die of renal failure (19). We have shown that the reduced longevity of fetally growth restricted, postnatally growth caught-up male rats is associated with accelerated shortening of telomeres in the kidney (21). We have suggested that this shortening is associated with accelerated senescence of renal cells with earlier renal failure and death.…”

Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?

“…Relatively little attention has been paid to the effects of disease models on telomeres in rodents, perhaps because of the known differences in telomere length and telomerase activity among human and rodent species [18,[23][24][25][26]. Notwithstanding the species differences, data implying a pathogenic role of telomere shortening in several forms of human pathology suggest that assessment of the effects of disease models on rodent telomeres may provide important insights into the relationship between telomeres and disease processes.…”

“…Blots were exposed to X-Ray film for 10-60 seconds. Mean TRF length and % photo-stimulated luminescence were determined from densitometric analysis of digital images of exposed films as described [18]. Measurements of TRF length were performed in duplicate for each liver.…”

“…The first method assesses mean telomere length. The second method evaluates the distribution of telomere lengths, on the premise that the presence of critically shortened telomeres which are biologically significant may not be reflected by mean telomere lengths [18]. No difference in mean telomere length was observed between the control and iron-loaded livers (Fig.…”