Effect of Physical Activity on the Circadian System: Comparison
Please note this is a comparison between Version 2 by Lindsay Dong and Version 1 by Denis Gubin.

Circadian rhythms are an inherent property of all living systems and an essential part of the external and internal temporal order. They enable organisms to be synchronized with their periodic environment and guarantee the optimal functioning of organisms. Any disturbances, so-called circadian disruptions, may have adverse consequences for health, physical and mental performance, and wellbeing. The environmental light–dark cycle is the main zeitgeber for circadian rhythms. Moreover, regular physical activity is most useful. Not only does it have general favorable effects on the cardiovascular system, the energy metabolism and mental health, for example, but it may also stabilize the circadian system via feedback effects on the suprachiasmatic nuclei (SCN), the main circadian pacemaker. Regular physical activity helps to maintain high-amplitude circadian rhythms, particularly of clock gene expression in the SCN. It promotes their entrainment to external periodicities and improves the internal synchronization of various circadian rhythms. This in turn promotes health and wellbeing.

  • motor activity
  • circadian rhythms
  • circadian disruption
  • health
  • wellbeing
  • physical and mental performance

1. Introduction

Circadian rhythms are an inherent property of all living systems and are generated by an internal clock. In mammals, this is localized in the suprachiasmatic nuclei (SCN) of the hypothalamus [1]. The SCN as central pacemakers are involved in the rhythmic regulation of sleep–wake behavior [2], locomotor activity [3], metabolism [4], body temperature [5], and other body functions.
Circadian rhythms are an essential part of the external and internal temporal order. They enable organisms to be synchronized with their periodic environment, to be prepared for rather than react to periodic changes and coordinate physiological and behavioral processes. This guarantees an optimal functioning, and any disturbances, or so-called circadian disruptions, may have adverse consequences for health, physical and mental performance, wellbeing, and longevity [6,7,8,9,10][6][7][8][9][10]. Such disruptions do occur during aging [11,12,13[11][12][13][14],14], following time-zone transitions [15,16[15][16][17],17], in shift-workers [18[18][19],19], and in subjects suffering from different diseases [20,21,22,23][20][21][22][23]. However, in the latter case, it is not clear if circadian disruptions are a consequence of the disease or a cause.
Therefore, it is highly important to find approaches to synchronize circadian rhythms and, thus, stabilize the entire circadian system. Melatonin, as an effective chronobiotic, is often used [24]. However, the physiological effects of melatonin depend critically on dosing and timing. For chronobiotic purposes, physiologic doses (3 mg or less) are useful, while higher doses (3–10 mg or more) exert antioxidant and immunoregulatory effects [25,26][25][26]. Optimal dosing may be different between individuals. Even more important could be a personal adjustment of timing, since physiological responses to melatonin follow phase response curves [27]. When non-physiological doses have to be used, one must consider adverse side effects. Accordingly, non-pharmacological approaches may be preferred, except, for example, in very old people where the use of melatonin might be unavoidable [28,29][28][29]. The daily light–dark cycle is the main zeitgeber [30,31][30][31]. It synchronizes circadian rhythms with the 24-h environment. In ourthe modern society, however, most people are exposed to only low levels of light in the daytime. On the contrary, the light levels in the evening or at night are often too high. Both have adverse consequences for the synchronization of the circadian rhythms with the 24-h environment and multiple negative effects on physiology, sleep, physical and mental performance, and well-being [19,32,33,34,35][19][32][33][34][35]. Food can also serve as a synchronizer for the circadian system. Timed feeding may reset the SCN phase via a reinforcement of clock gene expression, entrain peripheral clocks, and facilitate intrinsic synchronization [39,40,41,42][36][37][38][39]. Thus, it can be used to strengthen the circadian system, which in turn promotes healthy aging and longevity [21,43,44][21][40][41]. Robust circadian clocks can also be facilitated by lifestyle, regular physical activity, and timed exercise. Aged people often adopt, although rather intuitively, a regular lifestyle [45,46][42][43]. However, a problem of ourthe modern society is a general low level of physical activity [47][44]. This has adverse consequences for the cardiovascular system and the energy metabolism [48][45]. Moreover, direct effects on homeostatic physiological mechanisms and disturbances of the circadian system have a considerable impact. Scheduled physical activity is an efficient strategy to maintain circadian rhythms and contribute to healthy ageing [12,13,49][12][13][46]. It upholds feedback coupling with the central brain clock and helps to preserve synchronized circadian rhythms [10,50][10][47].

2. Physical Activity and the Circadian System

2.1. The Diagnostic Value of Circadian Activity Rhythms

In humans, activity can be monitored easily over many days and at short sampling intervals by means of non-invasive devices worn on the wrist of the non-dominant hand [51][48]. This method is widely used in field research and in clinical settings, as it is simple, inexpensive, and rather accurate [52,53,54][49][50][51]. In laboratory animals, motor activity can be monitored by transmitters that are implanted into the peritoneal cavity and allowing the simultaneous recording of core body temperature [55][52]. Moreover, most reliable and less expensive are passive infrared motion detectors that are mounted above the cage roof [56][53]. Both methods record general activity, not just locomotion. The wide use of actimetry monitoring techniques makes circadian activity rhythm assessment a useful tool to survey circadian rhythm robustness [57,58][54][55]. Moreover, rhythm characteristics can be used as indicators of physical and mental fitness and the health status of human beings. Vitale and co-authors [59][56] used actigraphy to characterize the activity level and the daily activity rhythm of patients following hip and knee joint replacement and designed specific, personalized rehabilitation programs. The inter-daily rhythm stability and the median level of daytime activity were found to be negatively correlated with cognitive decline and depression in elderly women [53][50]. Other authorscholars compared the amounts of activity when in bed or out of bed. This can be a preferable option when the 24-h pattern is non-sinusoidal. The estimated dichotomy indices were decreased in diseased individuals, particularly in those suffering from colorectal cancer [54,60][51][57]. Together with the mean activity level and autocorrelation coefficients, they are an objective indicator of physical welfare and an appropriate prognostic factor for cancer patients´ survival and tumour response [61,62,63][58][59][60]. According to Hoopes et al., characteristics of the rest–activity rhythm, especially the inter-daily stability and intra-daily variability, can be used as biomarkers of cardiometabolic health [64][61]. Irregular sleep duration and timing were recognized as novel cardiovascular risk factors, independent of other traditional factors and sleep quantity or quality [65][62]. An increased fragmentation of the 24-h activity rhythm is also positively associated with symptoms of food addiction [66][63]. Differences in the period length of the free-running activity rhythm were found in spontaneous hypertensive rats as compared to healthy controls [23]. Remarkably, changes occurred in the pre-hypertensive state already and not after the surgical induction of hypertension. In glaucoma patients, the sleep–wake rhythm was found to be compromised [67][64].

2.2. Beneficial Effects of Increasing the Daily Activity Level

Worldwide, a high percentage of people is physically inactive, especially in high-income countries, and this percentage increases with age [47,77][44][65]. The scarce physical activity of elderly people is at least partly caused by sarcopenia, though its progression can be reduced by regular exercise [78,79][66][67]. Physical inactivity is one of the most important factors causing lifestyle diseases. It substantially increases the risk of adverse health conditions and shortens life expectancy. Particularly, the incidence of coronary heart disease, metabolic diseases such as obesity and type 2 diabetes, and also breast and colon cancers has been shown to be elevated. Accordingly, a physically active behavior could improve health and has a protective effect on the development of diseases [48,80,81][45][68][69]. The improvement of methods to record physical activity might help to develop programs to enhance activity levels and, thus, reduce the risk of non-communicable diseases. Regular exercise helps to prevent cardiovascular disease [82][70], stroke [83][71], cancer [84][72], diabetes, and obesity [85][73]. It also has positive effects in patients suffering from neuropsychiatric disturbances. Aside from psychological mechanisms such as improved sleep and stress reduction, neurobiological mechanisms such as changes in neurotransmitter concentrations are also involved [86,87][74][75]. Exercise can prevent the development of stress-related mood disorders such as depression and anxiety and promote self-confidence. Animal models were used to elucidate the underlying mechanisms [88][76]. In Syrian hamsters, voluntary exercise promotes resilience to social defeat; animals are less anxious and show less defensive/submissive behaviors [89][77]. Physical activity positively influences cognitive function in patients with dementia, i.e., it decelerates the cognitive decline [90,91][78][79]. Experiments in rodents revealed that physical exercise regulates hippocampal neurogenesis, especially if it is performed in the context of cognitive challenges, and reduces learning deficits [92,93,94,95,96][80][81][82][83][84].

2.3. Effects of Motor Activity on the Circadian System

It has been well known for many years that motor activity has a considerable impact on circadian rhythms, via a feedback effect on the central pacemaker, the SCN. A correlation between activity level and the period length of the rhythm generated in the SCN was found [56,97,98][53][85][86]. Intensive running wheel use also affects photic phase responses [99,100,101][87][88][89]. Bouts of physical activity may cause phase changes—so-called non-photic phase responses. Depending on the circadian time, activity bouts may cause a phase advance or a phase delay. Mrosovsky first published a non-photic phase response curve [102][90]. In Golden hamsters for example, a bout of motor activity in the middle of the light time, i.e., during the subjective day, causes a phase advance. The animals’ next activity period starts earlier, i.e., the animals “wake up” and “go to sleep” earlier. Similar effects were described for humans [103][91]. One hour of moderate treadmill exercise for three consecutive days caused significant phase changes of the urinary aMT6s rhythm, the metabolic end-product of melatonin. Motor activity and behavioral states may directly influence the neurophysiological properties of the SCN and affect clock genes expression [104,105,106,107][92][93][94][95]. This may be the causal reason for the above-mentioned changes in photic phase responses and free-running periods. In humans, personalized timing, duration, and the type of exercise should enhance its benefits, particularly for cardiovascular health [119][96]. Evening exercise might be less beneficial [120][97]. Moreover, benefits may vary depending on chronotype [121,122][98][99], or when metabolic circadian rhythms are compromised in diseases such as diabetes [123][100]. Overall, considering the timing of exercise can be important in performance and disease contexts to improve circadian alignment and health status as a therapeutic and preventative strategy [124][101]. In humans, physical activity closely associates with time spent outdoors [125][102]. Time outdoors was a factor of higher physical activity during COVID-19 mandated lockdown [126][103]. It was also linked with better sleep, a higher quality of life, and less pronounced phase delay, which was common during lockdown for the majority of the population [126][103]. It this context, it should be outlined that outdoor activity is related to outdoor light exposure, and these factors act together in facilitating circadian alignment and robustness. Overall, more outdoor time can be linked with a more active lifestyle and lower chronic disease risks [125,126][102][103].

2.4. Beneficial Effects of Stabilized Circadian Rhythms

Physical activity has a strong impact on circadian rhythms, Figure 1. In rodents, it has been shown that voluntary access to a running wheel helps to maintain the high-amplitude circadian rhythms of clock and clock-controlled genes in the SCN. Similar effects can also be expected to occur in humans. As a consequence of high-amplitude circadian rhythms in the SCN, their rhythmic output that controls overt rhythms and peripheral oscillators is strengthened. Proper internal and external phase relationships can be established, and a circadian disruption be abolished [109,117][104][105]. This reduces the risk of diseases.
Figure 1.
Daytime activity facilitates robust circadian rhythms and promotes health and well-being: schematic overview.


  1. Reppert, S.M.; Weaver, D.R. Coordination of circadian timing in mammals. Nature 2002, 418, 935–941.
  2. Dijk, D.J.; Lockley, S.W. Integration of human sleep-wake regulation and circadian rhythmicity. J. Appl. Physiol. 2002, 92, 852–862.
  3. Wollnik, F.; Turek, F.W. SCN lesions abolish ultradian and circadian components of activity rhythms in LEW/Ztm rats. Am. J. Physiol. 1989, 256, R1027–R1039.
  4. Kalsbeek, A.; Scheer, F.A.; Perreau-Lenz, S.; La Fleur, S.E.; Yi, C.X.; Fliers, E.; Buijs, R.M. Circadian disruption and SCN control of energy metabolism. FEBS Lett. 2011, 585, 1412–1426.
  5. Waterhouse, J.; Drust, B.; Weinert, D.; Edwards, B.; Gregson, W.; Atkinson, G.; Kao, S.; Aizawa, S.; Reilly, T. The circadian rhythm of core temperature: Origin and some implications for exercise performance. Chronobiol. Int. 2005, 22, 207–225.
  6. Hurd, M.W.; Ralph, M.R. The significance of circadian organization for longevity in the golden hamster. J. Biol. Rhythm. 1998, 13, 430–436.
  7. Müller, L.; Weinert, D. Individual recognition of social rank and social memory performance depends on a functional circadian system. Behav Process. 2016, 132, 85–93.
  8. Sharma, A.; Tiwari, S.; Singaravel, M. Circadian rhythm disruption: Health consequences. Biol. Rhythm Res. 2015, 47, 191–213.
  9. Smolensky, M.H.; Hermida, R.C.; Reinberg, A.; Sackett-Lundeen, L.; Portaluppi, F. Circadian disruption: New clinical perspective of disease pathology and basis for chronotherapeutic intervention. Chronobiol. Int. 2016, 33, 1101–1119.
  10. Weinert, D.; Schöttner, K.; Müller, L.; Wienke, A. Intensive voluntary wheel running may restore circadian activity rhythms and improves the impaired cognitive performance of arrhythmic Djungarian hamsters. Chronobiol. Int. 2016, 33, 1161–1170.
  11. Gubin, D.G.; Weinert, D. Temporal order deterioration and circadian disruption with age. 1. Central and peripheral mechanisms. Adv. Gerontol. 2015, 5, 209–218.
  12. Gubin, D.G.; Weinert, D. Deterioration of Temporal Order and Circadian Disruption with Age 2: Systemic Mechanisms of Aging Related Circadian Disruption and Approaches to Its Correction. Adv. Gerontol. 2016, 6, 10–20.
  13. Gubin, D.G.; Weinert, D.; Bolotnova, T.V. Age-Dependent Changes of the Temporal Order—Causes and Treatment. Curr. Aging Sci. 2016, 9, 14–25.
  14. Weinert, D. Age-dependent changes of the circadian system. Chronobiol. Int. 2000, 17, 261–283.
  15. Casiraghi, L.P.; Oda, G.A.; Chiesa, J.J.; Friesen, W.O.; Golombek, D.A. Forced Desynchronization of Activity Rhythms in a Model of Chronic Jet Lag in Mice. J. Biol. Rhythm. 2012, 27, 59–69.
  16. Waterhouse, J.; Kao, S.; Edwards, B.; Weinert, D.; Atkinson, G.; Reilly, T. Transient changes in the pattern of food intake following a simulated time-zone transition to the east across eight time zones. Chronobiol. Int. 2005, 22, 299–319.
  17. Waterhouse, J.; Reilly, T.; Atkinson, G.; Edwards, B. Jet lag: Trends and coping strategies. Lancet 2007, 369, 1117–1129.
  18. Shurkevich, N.P.; Vetoshkin, A.S.; Gapon, L.I.; Dyachkov, S.M.; Gubin, D.G. Prognostic value of blood pressure circadian rhythm disturbances in normotensive shift workers of the Arctic polar region. Arter. Hypertens. 2017, 23, 36–46. (In Russian)
  19. Touitou, Y.; Reinberg, A.; Touitou, D. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. Life Sci. 2017, 173, 94–106.
  20. Gubin, D.G.; Nelaeva, A.A.; Uzhakova, A.E.; Hasanova, Y.V.; Cornelissen, G.; Weinert, D. Disrupted circadian rhythms of body temperature, heart rate and fasting blood glucose in prediabetes and type 2 diabetes mellitus. Chronobiol. Int. 2017, 34, 1136–1148.
  21. Kent, B.A. Synchronizing an aging brain: Can entraining circadian clocks by food slow Alzheimer’s disease? Front. Aging Neurosci. 2014, 6, 234.
  22. Neroev, V.; Malishevskaya, T.; Weinert, D.; Astakhov, S.; Kolomeichuk, S.; Cornelissen, G.; Kabitskaya, Y.; Boiko, E.; Nemtsova, I.; Gubin, D. Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma. Int. J. Mol. Sci. 2021, 22, 359.
  23. Yilmaz, A.; Kalsbeek, A.; Buijs, R.M. Functional changes of the SCN in spontaneous hypertension but not after the induction of hypertension. Chronobiol. Int. 2018, 35, 1221–1235.
  24. Cardinali, D.P. Melatonin as a chronobiotic/cytoprotector: Its role in healthy aging. Biol. Rhythm Res. 2019, 50, 28–45.
  25. Cardinali, D.P.; Brown, G.M.; Pandi-Perumal, S.R. Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients? Diseases 2020, 8, 44.
  26. Hardeland, R. Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies. Diseases 2021, 9, 18.
  27. Lewy, A.J.; Ahmed, S.; Jackson, J.M.; Sack, R.L. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol. Int. 1992, 9, 380–392.
  28. Gubin, D.G.; Gubin, G.D.; Gapon, L.I.; Weinert, D. Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms. Curr. Aging Sci. 2016, 9, 5–13.
  29. Gubin, D.G.; Gubin, G.D.; Waterhouse, J.; Weinert, D. The circadian body temperature rhythm in the elderly: Effect of single daily melatonin dosing. Chronobiol. Int. 2006, 23, 639–658.
  30. Daan, S. The Colin S. Pittendrigh Lecture. Colin Pittendrigh, Jurgen Aschoff, and the natural entrainment of circadian systems. J. Biol. Rhythm. 2000, 15, 195–207.
  31. Golombek, D.A.; Rosenstein, R.E. Physiology of circadian entrainment. Physiol. Rev. 2010, 90, 1063–1102.
  32. Cho, Y.; Ryu, S.-H.; Lee, B.R.; Kim, K.H.; Lee, E.; Choi, J. Effects of artificial light at night on human health: A literature review of observational and experimental studies applied to exposure assessment. Chronobiol. Int. 2015, 32, 1294–1310.
  33. Green, A.; Cohen-Zion, M.; Haim, A.; Dagan, Y. Evening light exposure to computer screens disrupts human sleep, biological rhythms, and attention abilities. Chronobiol. Int. 2017, 34, 855–865.
  34. Gubin, D.G.; Weinert, D.; Rybina, S.V.; Danilova, L.A.; Solovieva, S.V.; Durov, A.M.; Prokopiev, N.Y.; Ushakov, P.A. Activity, sleep and ambient light have a different impact on circadian blood pressure, heart rate and body temperature rhythms. Chronobiol. Int. 2017, 34, 632–649.
  35. Smolensky, M.H.; Sackett-Lundeen, L.L.; Portaluppi, F. Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases. Chronobiol. Int. 2015, 32, 1029–1048.
  36. Castillo, M.R.; Hochstetler, K.J.; Tavernier, R.J., Jr.; Greene, D.M.; Bult-Ito, A. Entrainment of the master circadian clock by scheduled feeding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 287, R551–R555.
  37. Froy, O.; Miskin, R. Effect of feeding regimens on circadian rhythms: Implications for aging and longevity. Aging 2010, 2, 7–27.
  38. Lamont, E.W.; Diaz, L.R.; Barry-Shaw, J.; Stewart, J.; Amir, S. Daily restricted feeding rescues a rhythm of period2 expression in the arrhythmic suprachiasmatic nucleus. Neuroscience 2005, 132, 245–248.
  39. Stokkan, K.A.; Yamazaki, S.; Tei, H.; Sakaki, Y.; Menaker, M. Entrainment of the circadian clock in the liver by feeding. Science 2001, 291, 490–493.
  40. Acosta-Rodriguez, V.A.; Rijo-Ferreira, F.; Green, C.B.; Takahashi, J.S. Importance of circadian timing for aging and longevity. Nat. Commun. 2021, 12, 2862.
  41. Mistlberger, R.E.; Antle, M.C. Entrainment of circadian clocks in mammals by arousal and food. Essays Biochem. 2011, 49, 119–136.
  42. Minors, D.; Atkinson, G.; Bent, N.; Rabbitt, P.; Waterhouse, J. The effects of age upon some aspects of lifestyle and implications for studies on circadian rhythmicity. Age Ageing 1998, 27, 67–72.
  43. Monk, T.H.; Reynolds, C.F., III; Kupfer, D.J.; Hoch, C.C.; Carrier, J.; Houck, P.R. Differences over the life span in daily life-style regularity. Chronobiol. Int. 1997, 14, 295–306.
  44. Hallal, P.C.; Andersen, L.B.; Bull, F.C.; Guthold, R.; Haskell, W.; Ekelund, U. Lancet Physical Activity Series Working G. Global physical activity levels: Surveillance progress, pitfalls, and prospects. Lancet 2012, 380, 247–257.
  45. Lee, I.M.; Shiroma, E.J.; Lobelo, F.; Puska, P.; Blair, S.N.; Katzmarzyk, P.T. Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy. Lancet 2012, 380, 219–229.
  46. de Souza Teixeira, A.A.; Lira, F.S.; Rosa-Neto, J.C. Aging with rhythmicity. Is it possible? Physical exercise as a pacemaker. Life Sci. 2020, 261, 118453.
  47. Weinert, D.; Waterhouse, J. The circadian rhythm of core temperature: Effects of physical activity and aging. Physiol. Behav. 2007, 90, 246–256.
  48. Bellone, G.J.; Plano, S.A.; Cardinali, D.P.; Chada, D.P.; Vigo, D.E.; Golombek, D.A. Comparative analysis of actigraphy performance in healthy young subjects. Sleep Sci. 2016, 9, 272–279.
  49. Ancoli-Israel, S.; Cole, R.; Alessi, C.; Chambers, M.; Moorcroft, W.; Pollak, C.P. The role of actigraphy in the study of sleep and circadian rhythms. Sleep 2003, 26, 342–392.
  50. Carvalho-Bos, S.S.; Riemersma-van der Lek, R.F.; Waterhouse, J.; Reilly, T.; Van Someren, E.J. Strong association of the rest-activity rhythm with well-being in demented elderly women. Am. J. Geriatr. Psychiatry 2007, 15, 92–100.
  51. Chevalier, V.; Mormont, M.C.; Cure, H.; Chollet, P. Assessment of circadian rhythms by actimetry in healthy subjects and patients with advanced colorectal cancer. Oncol. Rep. 2003, 10, 733–737.
  52. Weinert, D.; Sturm, J.; Waterhouse, J. Different behavior of the circadian rhythms of activity and body temperature during resynchronization following an advance of the LD cycle. Biol. Rhythm Res. 2002, 33, 187–197.
  53. Weinert, D.; Weiss, T. A nonlinear interrelationship between period length and the amount of activity—Age-dependent changes. Biol. Rhythm Res. 1997, 28, 105–120.
  54. Gubin, D.; Weinert, D.; Cornélissen, G. Chronotheranostics and chronotherapy—Frontiers for personalized medicine. J. Chronomed. 2020, 22, 3–23.
  55. Martinez-Nicolas, A.; Madrid, J.A.; García, F.J.; Campos, M.; Moreno-Casbas, M.T.; Almaida-Pagán, P.F.; Lucas-Sánchez, A.; Rol, M.A. Circadian monitoring as an aging predictor. Sci. Rep. 2018, 8, 15027.
  56. Vitale, J.A.; Banfi, G.; Tivolesi, V.; Pelosi, C.; Borghi, S.; Negrini, F. Rest-activity daily rhythm and physical activity levels after hip and knee joint replacement: The role of actigraphy in orthopedic clinical practice. Chronobiol. Int. 2021, 38, 1692–1701.
  57. Minors, D.; Akerstedt, T.; Atkinson, G.; Dahlitz, M.; Folkard, S.; Levi, F.; Mormont, C.; Parkes, D.; Waterhouse, J. The difference between activity when in bed and out of bed. I. Healthy subjects and selected patients. Chronobiol. Int. 1996, 13, 27–34.
  58. Mormont, M.C.; Langouet, A.M.; Claustrat, B.; Bogdan, A.; Marion, S.; Waterhouse, J.; Touitou, Y.; Levi, F. Marker rhythms of circadian system function: A study of patients with metastatic colorectal cancer and good performance status. Chronobiol. Int. 2002, 19, 141–155.
  59. Mormont, M.C.; Waterhouse, J. Contribution of the rest-activity circadian rhythm to quality of life in cancer patients. Chronobiol. Int. 2002, 19, 313–323.
  60. Mormont, M.C.; Waterhouse, J.; Bleuzen, P.; Giacchetti, S.; Jami, A.; Bogdan, A.; Lellouch, J.; Misset, J.L.; Touitou, Y.; Levi, F. Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status. Clin. Cancer Res. 2000, 6, 3038–3045.
  61. Hoopes, E.K.; Witman, M.A.; D’Agata, M.N.; Berube, F.R.; Brewer, B.; Malone, S.K.; Grandner, M.A.; Patterson, F. Rest-activity rhythms in emerging adults: Implications for cardiometabolic health. Chronobiol. Int. 2021, 38, 543–556.
  62. Huang, T.; Mariani, S.; Redline, S. Sleep Irregularity and Risk of Cardiovascular Events. J. Am. Coll. Cardiol. 2020, 75, 991–999.
  63. Borisenkov, M.; Tserne, T.; Bakutova, L.; Gubin, D. Food Addiction and Emotional Eating Are Associated with Intradaily Rest–Activity Rhythm Variability. Eat Weight Disord. 2022.
  64. Gubin, D.G.; Malishevskaya, T.N.; Astakhov, Y.S.; Astakhov, S.Y.; Cornelissen, G.; Kuznetsov, V.A.; Weinert, D. Progressive retinal ganglion cell loss in primary open-angle glaucoma is associated with temperature circadian rhythm phase delay and compromised sleep. Chronobiol. Int. 2019, 36, 564–577.
  65. Charansonney, O.L. Physical activity and aging: A life-long story. Discov. Med. 2011, 12, 177–185.
  66. Choi, Y.; Cho, J.; No, M.-H.; Heo, J.-W.; Cho, E.-J.; Chang, E.; Park, D.-H.; Kang, J.-H.; Kwak, H.-B. Re-Setting the Circadian Clock Using Exercise against Sarcopenia. Int. J. Mol. Sci. 2020, 21, 3106.
  67. Kume, Y.; Kodama, A.; Maekawa, H. Preliminary report; Comparison of the circadian rest-activity rhythm of elderly Japanese community-dwellers according to sarcopenia status. Chronobiol. Int. 2020, 37, 1099–1105.
  68. Balbus, J.M.; Barouki, R.; Birnbaum, L.S.; Etzel, R.A.; Gluckman, P.D.; Grandjean, P.; Hancock, C.; Hanson, M.A.; Heindel, J.J.; Hoffman, K.; et al. Early-life prevention of non-communicable diseases. Lancet 2013, 38, 3–4.
  69. Kelly, S.A.; Pomp, D. Genetic determinants of voluntary exercise. Trends Genet. 2013, 29, 348–357.
  70. Stensel, D. Primary prevention of CVD: Physical activity. BMJ Clin. Evid. 2009, 2009, 0218.
  71. Gallanagh, S.; Quinn, T.J.; Alexander, J.; Walters, M.R. Physical activity in the prevention and treatment of stroke. ISRN Neurol. 2011, 2011, 953818.
  72. Denlinger, C.S.; Engstrom, P.F. Colorectal cancer survivorship: Movement matters. Cancer Prev. Res. 2011, 4, 502–511.
  73. Wadden, T.A.; Webb, V.L.; Moran, C.H.; Bailer, B.A. Lifestyle modification for obesity: New developments in diet, physical activity, and behavior therapy. Circulation 2012, 125, 1157–1170.
  74. Matura, S.; Carvalho, A.F.; Alves, G.S.; Pantel, J. Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer’s Dementia: Possible Mechanisms, Current Evidence and Future Directions. Curr. Alzheimer Res. 2016, 13, 1112–1123.
  75. Vyazovskiy, V.V.; Ruijgrok, G.; Deboer, T.; Tobler, I. Running wheel accessibility affects the regional electroencephalogram during sleep in mice. Cereb. Cortex. 2006, 16, 328–336.
  76. Greenwood, B.N.; Fleshner, M. Exercise, learned helplessness, and the stress-resistant brain. Neuromol. Med. 2008, 10, 81–98.
  77. Kingston, R.C.; Smith, M.; Lacey, T.; Edwards, M.; Best, J.N.; Markham, C.M. Voluntary exercise increases resilience to social defeat stress in Syrian hamsters. Physiol. Behav. 2018, 188, 194–198.
  78. Groot, C.; Hooghiemstra, A.M.; Raijmakers, P.G.H.M.; van Berckel, B.N.M.; Scheltens, P.; Scherder, E.J.A.; van der Flier, W.M.; Ossenkoppele, R. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res. Rev. 2016, 25, 13–23.
  79. Winchester, J.; Dick, M.B.; Gillen, D.; Reed, B.; Miller, B.; Tinklenberg, J.; Mungas, D.; Chui, H.; Galasko, D.; Hewett, L.; et al. Walking stabilizes cognitive functioning in Alzheimer’s disease (AD) across one year. Arch. Gerontol. Geriatr. 2013, 56, 96–103.
  80. Fabel, K.; Kempermann, G. Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromol. Med. 2008, 10, 59–66.
  81. Feter, N.; Spanevello, R.M.; Soares, M.S.P.; Spohr, L.; Pedra, N.S.; Bona, N.P.; Freitas, M.P.; Gonzales, N.G.; Ito, L.G.M.S.; Stefanello, F.M.; et al. How does physical activity and different models of exercise training affect oxidative parameters and memory? Physiol. Behav. 2019, 201, 42–52.
  82. Mustroph, M.L.; Chen, S.; Desai, S.C.; Cay, E.B.; DeYoung, E.K.; Rhodes, J.S. Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice. Neuroscience 2012, 219, 62–71.
  83. Rajizadeh, M.A.; Esmaeilpour, K.; Masoumi-Ardakani, Y.; Bejeshk, M.A.; Shabani, M.; Nakhaee, N.; Ranjbar, M.P.; Borzadaran, F.M.; Sheibani, V. Voluntary exercise impact on cognitive impairments in sleep-deprived intact female rats. Physiol. Behav. 2018, 188, 58–66.
  84. van Praag, H.; Christie, B.R.; Sejnowski, T.J.; Gage, F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. USA 1999, 96, 13427–13431.
  85. Edgar, D.M.; Kilduff, T.S.; Martin, C.E.; Dement, W.C. Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice. Physiol. Behav. 1991, 50, 373–378.
  86. Weinert, D.; Schöttner, K. An inbred lineage of Djungarian hamsters with a strongly attenuated ability to synchronize. Chronobiol. Int. 2007, 24, 1065–1079.
  87. Antle, M.C.; Sterniczuk, R.; Smith, V.M.; Hagel, K. Non-photic modulation of phase shifts to long light pulses. J. Biol. Rhythm. 2007, 22, 524–533.
  88. Ralph, M.R.; Mrosovsky, N. Behavioral inhibition of circadian responses to light. J. Biol. Rhythm. 1992, 7, 353–359.
  89. Steinlechner, S.; Stieglitz, A.; Ruf, T. Djungarian hamsters: A species with a labile circadian pacemaker? Arrhythmicity under a light-dark cycle induced by short light pulses. J. Biol. Rhythm. 2002, 17, 248–258.
  90. Mrosovsky, N.; Salmon, P.A.; Menaker, M.; Ralph, M.R. Nonphotic phase shifting in hamster clock mutants. J. Biol. Rhythm. 1992, 7, 41–49.
  91. Youngstedt, S.D.; Elliott, J.A.; Kripke, D.F. Human circadian phase-response curves for exercise. J. Physiol. 2019, 597, 2253–2268.
  92. Deboer, T.; Vansteensel, M.J.; Detari, L.; Meijer, J.H. Sleep states alter activity of suprachiasmatic nucleus neurons. Nat. Neurosci. 2003, 6, 1086–1090.
  93. Maywood, E.S.; Okamura, H.; Hastings, M.H. Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nuclei. Eur. J. Neurosci. 2002, 15, 216–220.
  94. Schaap, J.; Meijer, J.H. Opposing effects of behavioural activity and light on neurons of the suprachiasmatic nucleus. Eur. J. Neurosci. 2001, 13, 1955–1962.
  95. Song, Y.; Choi, G.; Jang, L.; Kim, S.-W.; Jung, K.-H.; Park, H. Circadian rhythm gene expression and daily melatonin levels vary in athletes and sedentary males. Biol. Rhythm Res. 2018, 49, 237–245.
  96. Hower, I.M.; Harper, S.A.; Buford, T.W. Circadian Rhythms, Exercise, and Cardiovascular Health. J. Circadian Rhythm. 2018, 16, 7.
  97. Rubio-Sastre, P.; Gómez-Abellán, P.; Martinez-Nicolas, A.; Ordovás, J.M.; Madrid, J.A.; Garaulet, M. Evening physical activity alters wrist temperature circadian rhythmicity. Chronobiol. Int. 2014, 31, 276–282.
  98. Duglan, D.; Lamia, K.A. Clocking In, Working Out: Circadian Regulation of Exercise Physiology. Trends Endocrinol. Metab. 2019, 30, 347–356.
  99. Thomas, J.M.; Kern, P.A.; Bush, H.M.; McQuerry, K.J.; Black, W.S.; Clasey, J.L.; Pendergast, J.S. Circadian rhythm phase shifts caused by timed exercise vary with chronotype. JCI Insight 2020, 5, e134270.
  100. Heden, T.D.; Kanaley, J.A. Syncing Exercise with Meals and Circadian Clocks. Exerc. Sport Sci. Rev. 2019, 47, 22–28.
  101. Lewis, P.; Korf, H.W.; Kuffer, L.; Groß, J.V.; Erren, T.C. Exercise time cues (zeitgebers) for human circadian systems can foster health and improve performance: A systematic review. BMJ Open Sport Exerc. Med. 2018, 4, e000443.
  102. Beyer, K.M.M.; Szabo, A.; Hoormann, K.; Stolley, M. Time spent outdoors, activity levels, and chronic disease among American adults. J. Behav. Med. 2018, 41, 494–503.
  103. Korman, M.; Tkachev, V.; Reis, C.; Komada, Y.; Kitamura, S.; Gubin, D.; Kumar, V.; Roenneberg, T. Outdoor daylight exposure and longer sleep promote wellbeing under COVID-19 mandated restrictions. J. Sleep Res. 2022, 31, e13471.
  104. Leise, T.L.; Harrington, M.E.; Molyneux, P.C.; Song, I.; Queenan, H.; Zimmerman, E.; Lall, G.S.; Biello, S.M. Voluntary exercise can strengthen the circadian system in aged mice. Age 2013, 35, 2137–2152.
  105. Power, A.; Hughes, A.T.; Samuels, R.E.; Piggins, H.D. Rhythm-promoting actions of exercise in mice with deficient neuropeptide signaling. J. Biol. Rhythm. 2010, 25, 235–246.