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

Contributed by H. Eugene Stanley, December 31, 2014 (sent for review February 3, 2014; reviewed by Gene D. Block and Thomas Penzel)
February 9, 2015
112 (8) 2320-2324

Significance

Healthy systems are characterized by scale invariance across multiple timescales. We investigated whether loss of scale invariance that occurs with aging and disease can be counteracted by exercise, in four age groups of mice. Surprisingly, we observed that lack of exercise was detrimental not only in old but also in young mice, raising the possibility of an unforeseen role of behavioral activity for health in aged and young subjects alike. Moreover, we show that scale invariance could be restored by high levels of exercise, even in old animals. The World Health Organization has pinpointed lack of exercise and a sedentary lifestyle as a major risk factor for various diseases. Our measures may guide health programs.

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.

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Acknowledgments

We thank H. Post-van Engeldorp Gastelaars for excellent technical support. This research was supported by the European Commission Grant EUCLOCK (018741) (to J.H.M.), by the Netherlands Organization for Scientific Research TOPGO Grant 818.02.016 (to J.H.M.), and by Dutch Diabetes Research Foundation Grant 2013.81.1663 (to C.P.C.). K.H. is supported by NIH Grants R00-HL102241 and P01AG009975. F.A.J.L.S. was supported in part by NIH Grants R01 HL094806 and R01 HL118601. H.E.S. thanks the National Science Foundation Cyber-Enabled Discover and Innovation program for support under Award 1125290, and NIH for support under Award 5R01AG021133.

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References

1
AL Goldberger, et al., Fractal dynamics in physiology: Alterations with disease and aging. Proc Natl Acad Sci USA 99, 2466–2472 (2002).
2
CK Peng, et al., Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease. J Electrocardiol 28, 59–65 (1995).
3
CK Peng, S Havlin, HE Stanley, AL Goldberger, Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos 5, 82–87 (1995).
4
A Proekt, JR Banavar, A Maritan, DW Pfaff, Scale invariance in the dynamics of spontaneous behavior. Proc Natl Acad Sci USA 109, 10564–10569 (2012).
5
AL Barabási, The origin of bursts and heavy tails in human dynamics. Nature 435, 207–211 (2005).
6
CK Peng, et al., Quantifying fractal dynamics of human respiration: Age and gender effects. Ann Biomed Eng 30, 683–692 (2002).
7
K Hu, FA Scheer, PCh Ivanov, RM Buijs, SA Shea, The suprachiasmatic nucleus functions beyond circadian rhythm generation. Neuroscience 149, 508–517 (2007).
8
K Hu, et al., Fractal patterns of neural activity exist within the suprachiasmatic nucleus and require extrinsic network interactions. PLoS One 7, e48927 (2012).
9
K Hu, FA Scheer, RM Buijs, SA Shea, The endogenous circadian pacemaker imparts a scale-invariant pattern of heart rate fluctuations across time scales spanning minutes to 24 hours. J Biol Rhythms 23, 265–273 (2008).
10
LY Lin, et al., Detrended fluctuation analysis predicts successful defibrillation for out-of-hospital ventricular fibrillation cardiac arrest. Resuscitation 81, 297–301 (2010).
11
JM Hausdorff, et al., Altered fractal dynamics of gait: Reduced stride-interval correlations with aging and Huntington’s disease. J Appl Physiol (1985) 82, 262–269 (1997).
12
K Hu, EJ Van Someren, SA Shea, FA Scheer, Reduction of scale invariance of activity fluctuations with aging and Alzheimer’s disease: Involvement of the circadian pacemaker. Proc Natl Acad Sci USA 106, 2490–2494 (2009).
13
AJ Macintosh, CL Alados, MA Huffman, Fractal analysis of behaviour in a wild primate: Behavioural complexity in health and disease. J R Soc Interface 8, 1497–1509 (2011).
14
BR Pittman-Polletta, FA Scheer, MP Butler, SA Shea, K Hu, The role of the circadian system in fractal neurophysiological control. Biol Rev Camb Philos Soc 88, 873–894 (2013).
15
MJ Vansteensel, S Michel, JH Meijer, Organization of cell and tissue circadian pacemakers: A comparison among species. Brain Res Brain Res Rev 58, 18–47 (2008).
16
ME Harrington, Exercise strengthens circadian clocks. J Physiol 590, 5929 (2012).
17
AM Schroeder, et al., Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice. J Physiol 590, 6213–6226 (2012).
18
F van Oosterhout, et al., Amplitude of the SCN clock enhanced by the behavioral activity rhythm. PLoS One 7, e39693 (2012).
19
H Bruunsgaard, BK Pedersen, Special feature for the Olympics: Effects of exercise on the immune system: Effects of exercise on the immune system in the elderly population. Immunol Cell Biol 78, 523–531 (2000).
20
GS Passos, et al., Effects of moderate aerobic exercise training on chronic primary insomnia. Sleep Med 12, 1018–1027 (2011).
21
A McTiernan, Mechanisms linking physical activity with cancer. Nat Rev Cancer 8, 205–211 (2008).
22
BM Brown, JJ Peiffer, RN Martins, Multiple effects of physical activity on molecular and cognitive signs of brain aging: Can exercise slow neurodegeneration and delay Alzheimer’s disease? Mol Psychiatry 18, 864–874 (2013).
23
KI Erickson, et al., Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108, 3017–3022 (2011).
24
IM Lee, et al., Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy. Lancet; Lancet Physical Activity Series Working Group 380, 219–229 (2012).
25
PC Hallal, et al., Global physical activity levels: Surveillance progress, pitfalls, and prospects. Lancet; Lancet Physical Activity Series Working Group 380, 247–257 (2012).
26
VS Valentinuzzi, K Scarbrough, JS Takahashi, FW Turek, Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice. Am J Physiol 273, R1957–R1964 (1997).
27
S Farajnia, et al., Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock. J Neurosci 32, 5891–5899 (2012).
28
K Hu, DG Harper, SA Shea, EG Stopa, FA Scheer, Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia. Sci Rep 3, 2229 (2013).
29
WH Hsieh, et al., Simulated shift work in rats perturbs multiscale regulation of locomotor activity. J R Soc Interface 11, 20140318 (2014).
30
K Hu, FA Scheer, RM Buijs, SA Shea, The circadian pacemaker generates similar circadian rhythms in the fractal structure of heart rate in humans and rats. Cardiovasc Res 80, 62–68 (2008).
31
TL Leise, et al., Voluntary exercise can strengthen the circadian system in aged mice. Age (Dordr) 35, 2137–2152 (2013).
32
LK Fonken, RJ Nelson, Dim light at night increases depressive-like responses in male C3H/HeNHsd mice. Behav Brain Res 243, 74–78 (2013).
33
A Power, AT Hughes, RE Samuels, HD Piggins, Rhythm-promoting actions of exercise in mice with deficient neuropeptide signaling. J Biol Rhythms 25, 235–246 (2010).
34
AT Hughes, HD Piggins, Feedback actions of locomotor activity to the circadian clock. Prog Brain Res 199, 305–336 (2012).

Information & Authors

Information

Published in

The cover image for PNAS Vol.112; No.8
Proceedings of the National Academy of Sciences
Vol. 112 | No. 8
February 24, 2015
PubMed: 25675516

Classifications

Submission history

Published online: February 9, 2015
Published in issue: February 24, 2015

Keywords

  1. circadian rhythms
  2. wheel running
  3. behavioral activity
  4. multiple timescales
  5. aging

Acknowledgments

We thank H. Post-van Engeldorp Gastelaars for excellent technical support. This research was supported by the European Commission Grant EUCLOCK (018741) (to J.H.M.), by the Netherlands Organization for Scientific Research TOPGO Grant 818.02.016 (to J.H.M.), and by Dutch Diabetes Research Foundation Grant 2013.81.1663 (to C.P.C.). K.H. is supported by NIH Grants R00-HL102241 and P01AG009975. F.A.J.L.S. was supported in part by NIH Grants R01 HL094806 and R01 HL118601. H.E.S. thanks the National Science Foundation Cyber-Enabled Discover and Innovation program for support under Award 1125290, and NIH for support under Award 5R01AG021133.

Authors

Affiliations

Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
Claudia P. Coomans1
Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
Kun Hu
Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; and
Frank A. J. L. Scheer
Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; and
H. Eugene Stanley2 [email protected]
Departments of dPhysics,
Chemistry,
Biomedical Engineering, and
Physiology, Boston University, Boston, MA 02215
Johanna H. Meijer2 [email protected]
Department of Molecular Cell Biology, Laboratory for Neurophysiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;

Notes

2
To whom correspondence may be addressed. Email: [email protected], [email protected], or [email protected].
Author contributions: C.G., C.P.C., H.E.S., and J.H.M. designed experiments; C.P.C. performed experiments; C.G. analyzed data; and C.G., C.P.C., K.H., F.A.J.L.S., H.E.S., and J.H.M. wrote the paper.
Reviewers: G.D.B., University of California, Los Angeles; and T.P., University of Marburg.
1
C.G. and C.P.C. contributed equally to this work.

Competing Interests

The authors declare no conflict of interest.

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    Lack of exercise leads to significant and reversible loss of scale invariance in both aged and young mice
    Proceedings of the National Academy of Sciences
    • Vol. 112
    • No. 8
    • pp. 2293-E922

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