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

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.Many physiologic variables, such as heart rate, respiration, and locomotor activity, display scale-invariant or “fractal” properties, characterized by temporal structures that are similar across different timescales (1–6). Fractal patterns in physiological systems are intrinsic characteristics that are independent of external stimuli (7–9). The presence of fractal patterns is associated with health advantages, such as system integrity, as well as adaptability, and physiologic systems lose their scale invariance under diseased or aging conditions. The scale invariance in, for example, heart rate is reduced in congestive heart failure patients, and moreover, changes in fractal patterns have been demonstrated to be better predictors of morbidity and mortality than classical biomarkers (2, 3, 10).Detrended fluctuation analysis (DFA) is a widely used method to quantify correlations in nonstationary physiological time series, such as heart rate and gait (1–3, 11, 12). The DFA provides information on the amplitude of the fluctuations at different timescales. The correlation in the fluctuations is described by the scaling exponent α. A value of α close to 1.0 indicates a delicate balance between uncorrelated randomness (α = 0.5) and regularity (α = 1.5), and is observed in healthy physiological systems (1). Under pathological conditions such as Huntington’s disease and Alzheimer’s disease, the physiological fluctuations are measurably different from 1 and are either too random or too regular (11, 12).Locomotor activity in both humans and rodents displays scale-invariant fluctuations for timescales of seconds up to ∼24 h (8, 12, 13). The mechanism for generating scale-invariant activity patterns is not understood. Recent studies showed that scale-invariant activity patterns are disrupted with aging and in patients suffering from dementia (12). The degree of the disruption is strongly correlated with the circadian neurotransmitter content in the suprachiasmatic nucleus (SCN) (14), the master clock in mammals that regulates circadian rhythms in physiology and behavior (15).In the past few years, it has become increasingly clear that exercise is beneficial for the circadian system (16–18). Furthermore, exercise improves the immune system, helps to prevent obesity, cardiovascular disease, and type 2 diabetes mellitus, and improves memory (19–23). The World Health Organization has pinpointed a lack of exercise as a major risk factor for diseases, including metabolic, cardiovascular, and immune diseases (24, 25). The aim of the present study is to determine whether a lack of exercise affects age-related deterioration in scale invariance of locomotor activity and whether, in turn, enhanced activity levels can lead to improvement. We found that, unexpectedly, a lack of exercise leads to loss of scale invariance not only in aged but also in young animals. Following a period of inactivity, exercise resulted in complete restoration of scale invariance in young animals and substantial improvement in old animals.