Seasonal variation in telomerase activity and telomere dynamics in a hibernating rodent, the garden dormouse (Eliomys quercinus)

Abstract

Telomere dynamics in hibernating species are known to reflect seasonal changes in somatic maintenance. Throughout hibernation, the periodic states of rewarming, known as inter-bout euthermia or arousals, are associated with high metabolic costs including shortening of telomeres. In the active season, if high energetic resources are available, telomere length can be restored in preparation for the upcoming winter. The mechanism for telomere elongation has not been clearly demonstrated, although the action of the ribonucleoprotein complex, telomerase, has been implicated in many species. Here we tested for levels of telomerase activity in the garden dormouse (Eliomys quercinus) at different seasonal time points throughout the year and across ages from liver tissues of male juveniles to adults. We found that telomerase is active at high levels across seasons (during torpor and inter-bout euthermia, plus in the active season) but that there was a substantial decrease in activity in the month prior to hibernation. Telomerase levels were consistent across age groups and were independent of feeding regime and time of birth (early or late born). The changes in activity levels that we detected were broadly associated with changes in telomere lengths measured in the same tissues. We hypothesise that i) telomerase is the mechanism used by garden dormice for maintenance of telomeres and that ii) activity is kept at high levels throughout the year until pre-hibernation when resources are diverted to increasing fat reserves for overwintering. We found no evidence for a decrease in telomerase activity with age or a final increase in telomere length which has been detected in other hibernating rodents.

Keywords: biological ageing; euthermia; oxidative damage; somatic maintenance; torpor.

FIGURE 1

Comparison between TRAP assay concentrations at 25°C and 5°C, for 99 animals in the 25°C group and 105 animals in the 5°C group, the boxes show the 25th percentile, the median, and the 75th percentile (Interquartile Range/IQR), whiskers represent the 25th/75th percentile −/+ 1.5 * IQR; points outside of that range are outliers, asterisks indicate significant differences between groups: ‘***’ <0.001 ‘**’ <0.01 ‘*’ <0.05.

FIGURE 2

(A) TRAP assay concentration at 25°C for all four different seasons, showing that telomerase is present in all phases of the cycle and potentially active. Results represent the glm model (Gaussian distribution), with the response variable telomerase activity at 25°C (square root transformed) and state as the only explanatory variable. For visualisation purposes the plot is on the original scale representing the raw data. (B) RTL ratio for all four different seasons. Active and prehibernation seasons only include adult female and male garden dormice, torpor and IBE timepoints only include juvenile males. We cannot compare the different timepoints in a full model, due to these constraints. The R package emmeans (Lenth, 2023) was used for comparisons between groups, asterisks indicate significant differences: “***” <0.001 “**” <0.01 “*” <0.05. The boxes show the 25th percentile, the median, and the 75th percentile (Interquartile Range/IQR), whiskers represent the 25th/75th percentile −/+ 1.5 * IQR, points outside of that range are outliers.

FIGURE 3

Comparison of (A) Partial residual plot of the effect of male (blue) and female (red) adult garden dormice on the TA at 25°C compared between the active and prehibernation season. The underlying model accounts for the effects of body mass, early/late born and age of the animals in months and (B) Partial residual plot of the effect of early (green) and late (violet) born garden dormice on RTL comparing the active and prehibernation season, underlying model accounts for the effects of body mass and age of the animals in months. Predictions are back-transformed to the original response scale, whiskers show the standard errors, for each group on square root scale for the telomerase activity plot, asterisks indicate significant differences between groups: “***” <0.001 “**” <0.01 “*” <0.05.