PhD defence Lauren de Wit
Circadian timing and genome integrity in mammalian hibernation
Many mammals survive winter conditions or periods of food shortage by temporarily lowering their metabolism and body temperature in a state called torpor. Torpor can occur as daily torpor, lasting several hours in response to acute energetic challenges, or as deep, multi-day hibernation, in which torpor bouts lasting days to weeks are interrupted by brief periods of rewarming (arousals). Although torpor conserves energy, repeated cooling and rewarming may impose molecular costs, particularly to DNA.
This thesis investigates how mammals maintain genome integrity during torpor–arousal cycles and which factors influence DNA damage and recovery. In a mouse model of daily torpor (Chapter 2), the energetic route into torpor affected both metabolic strategy and subsequent recovery. Although caloric restriction and acute fasting induced similar torpor characteristics, DNA damage accumulated in both conditions but was repaired more rapidly following caloric restriction. This demonstrates that the energetic context of torpor influences post-torpor recovery.
In the hibernating garden dormouse (Eliomys quercinus) (Chapters 3 and 4), arousals were shown to be gated by a temperature-compensated circadian mechanism, even at low body temperatures. Ambient temperature also affected DNA damage dynamics. At 5°C, damage accumulated gradually and was accompanied by recruitment of the DNA repair protein 53BP1, whereas at 10°C, DNA damage was already high early in torpor while repair recruitment lagged behind. Together, these findings show that genome maintenance during torpor depends on energetic context, temperature, and internal timing. DNA damage can accumulate during torpor, while euthermic arousals provide critical opportunities for effective repair.