Lack of exercise leads to significant and reversible loss of scale invariance in both aged and young mice

Abstract

In healthy humans and other animals, behavioral activity exhibits scale invariance over multiple timescales from minutes to 24 h, whereas in aging or diseased conditions, scale invariance is usually reduced significantly. Accordingly, scale invariance can be a potential marker for health. Given compelling indications that exercise is beneficial for mental and physical health, we tested to what extent a lack of exercise affects scale invariance in young and aged animals. We studied six or more mice in each of four age groups (0.5, 1, 1.5, and 2 y) and observed an age-related deterioration of scale invariance in activity fluctuations. We found that limiting the amount of exercise, by removing the running wheels, leads to loss of scale-invariant properties in all age groups. Remarkably, in both young and old animals a lack of exercise reduced the scale invariance in activity fluctuations to the same level. We next showed that scale invariance can be restored by returning the running wheels. Exercise during the active period also improved scale invariance during the resting period, suggesting that activity during the active phase may also be beneficial for the resting phase. Finally, our data showed that exercise had a stronger influence on scale invariance than the effect of age. The data suggest that exercise is beneficial as revealed by scale-invariant parameters and that, even in young animals, a lack of exercise leads to strong deterioration in these parameters.

Keywords: aging; behavioral activity; circadian rhythms; multiple timescales; wheel running.

Fig. 1.

Time series of behavioral activity in one representative animal in the presence and absence of a running wheel shows 24-h rhythm in activity levels. The PIR scores the animal’s movement in the cage per 1 min, and higher levels of movement lead to a higher score for behavioral activity levels. The animals are kept in alternating 12-h intervals of light and dark. Gray background indicates lights off. In the absence of the running wheel, the pattern in behavioral activity was altered compared with the pattern in the presence of a running wheel: the amount of activity was reduced during the night (active period) and was increased during the day (rest period).

Fig. 2.

Removal of the running wheel as well as aging weakened the scale-invariant correlation of behavioral activity fluctuations. The scale-invariant correlation of behavioral activity was assessed in the presence or absence of a running wheel in four age groups: (A) 0.5 y, (B) 1 y, (C) 1.5 y, and (D) 2 y. The recorded PIR data of the last 9 d in the presence of running wheels and the first 9 d in the absence of running wheels were chosen for analysis. The data were averaged from at least six mice in each group.

Fig. 3.

(A) Voluntary exercise restored the scale-invariant correlation of behavioral activity fluctuations. The scaling exponent α₂ at timescales from ∼3 to 24 h obtained from the DFA versus experimental time in days. The scale-invariant correlation of behavioral activity was measured in the presence or absence of a running wheel in four age groups: 0.5 y, 1 y, 1.5 y, and 2 y. There were three successive stages in our recording: in the presence of the running wheels (day ≤27), after removal of the running wheels (day ≥28 and day ≤54) and after returning the running wheels (day ≥55). The deterioration in α₂ was apparent following removal of the running wheel in all age groups. In addition, directly following returning of the running wheel, α₂ improved in all age groups. Each data point is averaged from at least six mice in the same group. (B) Blocking the running wheel weakened the scale-invariant correlation of behavioral activity fluctuations similar as removing the wheel. The scale-invariant correlation of behavioral activity in response to blocking of the wheel was assessed in 0.5-y-old mice. The data were averaged from nine mice.

Fig. 4.

The scale-invariant correlation from ∼3 to 24 h in activity fluctuations in individual mice demonstrates the dependence of scale invariance on activity levels. Shown are separate curves for individual mice of (A) 0.5 y, (B) 1 y, (C) 1.5 y, and (D) 2 y. The mice expressed different numbers of running wheel revolutions, indicated in the middle of each panel. Values are the mean from before and after wheel removal, and expressed in kilometers per day. There was a small SE of the scaling exponent α₂ in the group of 0.5 and 1 y. There was a large SE in the group of 1.5 and 2 y. The activity levels of the aged animals were highly related to α₂. For visibility and comparison, six mice are shown for each age group. See Fig. S1 for all animals.