Abstract

Animals have to adjust their activities when faced with caloric restriction (CR) to deal with reduced energy intake. If CR is pronounced, allostasis can push individuals into alternate physiological states which can result in important health benefits across a wide range of taxa. Here we developed a new approach to determine the changes in behavioural phenotype associated with different levels of CR. We exposed C57BL/6 male mice to graded CR (from 0 to 40%) for three months and defined their behavioural phenotype using hidden Markov models of their movement and body temperature. All 40% CR mice exhibited a state-shift in behavioural phenotype and only some exposed to 30% CR did. We show for the first time that mice changed their activity characteristics rather than changed their activities. This new phenotyping approach provides an avenue to determine the mechanisms linking CR to healthspan.

Highlights

  • This aspect has received little attention to date[5]

  • The best models for all mice contained three activity states which could be characterised as relatively higher activity and higher body temperature, relatively lower activity and relatively very low activity and lower body temperature (Supplementary Table 2, Supplementary Figure 2)

  • We expected to see a change in the temporal dynamics of mouse activity as well as the emergence of a third activity state, torpor, in mice exposed to higher levels of CR

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Summary

Introduction

This aspect has received little attention to date[5]. It is a key characteristic because activity bout durations encapsulate the constraints individuals face to cease or instigate given activities. Such changes have been partially observed before with, for example, the onset of lowered body temperature associated with lowered activity levels[19,20] and its extreme form – torpor – in rodents[19,20]. In a given physiological state, a mouse would partition its behaviour in a series of activities and assort the time it spends in those different activities in order to meet the need of that state, given the environmental constraints (here CR) it faces This hidden process can be defined by describing activity states and the temporal dynamics of transition among those states ( informing the activity budget and bout durations the mouse achieves). We expected mice in an active state to move more and have a slightly higher body temperature since movement generates heat[24], mice in an inactive state to move less and have a slightly lower body temperature and mice in a torpor state to be even less active and display a large drop in body temperature

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