What doesn`t kill you, makes you stronger: Increased lifespan in hibernators despite DNA damage

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Omschrijving

Hibernation is an adaptation to cope with harsh environmental conditions through gross reduction of metabolism (torpor). In line with the rate of living hypothesis, hibernators show increased longevity. During hibernation, periods of torpor are alternated with short periods of high metabolism and euthermic body temperatures (arousals). Remarkably, extended DNA damage was found to accumulate during torpor and rapidly normalized during arousals in hibernating hamster. This DNA damage/repair during torpor and arousal cycles, may lead to genomic instability, which cannot be reconciled with the hibernators’ extended lifespan and absence of tumor genesis. Consequently, we hypothesize that hibernators have developed an evolutionary adaptive mechanism to deal with DNA breaks, either by deploying superior repair mechanisms or by clearing of damaged cells. This adaptive mechanism will be the main objective of this research in combination with its effects on longevity and senescence. Inducing torpor in mice (Mus musculus) has shown to increase DNA damage in a pilot study. One of the key challenges is to confirm that daily torpor induced by the work-for-food paradigm will induce similar DNA damage/repair mechanisms in mice, allowing for a wide range of molecular techniques. These results will be compared with an obligatory deep hibernator, the edible dormouse (Glis glis). This species is a record holder for hibernation and torpor duration. It allows us to experimentally assess the role of torpor and arousals in DNA damage/repair mechanisms and compare these results with the effects of daily torpor in the house mouse. These two animal models allow us to use a well-established molecular toolbox in the house mouse to find relevant and potentially novel modes of DNA repair as well as the possibility to find long term consequences of DNA damage during hibernation.
AcroniemAL-II
StatusGeëindigd
Effectieve start/einddatum01/10/201701/07/2023