Weak synchronization can alter circadian period length: implications for aging and disease conditions

Jihwan Myung; Sungho Hong; Christoph Schmal; Hélène Vitet; Mei-Yi Wu

doi:10.3389/fnins.2023.1242800

Weak synchronization can alter circadian period length: implications for aging and disease conditions

Front Neurosci. 2023 Sep 27:17:1242800. doi: 10.3389/fnins.2023.1242800. eCollection 2023.

Authors

Jihwan Myung^{1

2

3}, Sungho Hong³, Christoph Schmal⁴, Hélène Vitet^{1

2

5}, Mei-Yi Wu^{6

7

8

9}

Affiliations

¹ Graduate Institute of Mind, Brain and Consciousness (GIMBC), Taipei Medical University, Taipei City, Taiwan.
² Brain and Consciousness Research Centre (BCRC), TMU-Shuang Ho Hospital, New Taipei City, Taiwan.
³ Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
⁴ Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
⁶ Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
⁷ Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁸ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁹ TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.

Abstract

The synchronization of multiple oscillators serves as the central mechanism for maintaining stable circadian rhythms in physiology and behavior. Aging and disease can disrupt synchronization, leading to changes in the periodicity of circadian activities. While our understanding of the circadian clock under synchronization has advanced significantly, less is known about its behavior outside synchronization, which can also fall within a predictable domain. These states not only impact the stability of the rhythms but also modulate the period length. In C57BL/6 mice, aging, diseases, and removal of peripheral circadian oscillators often result in lengthened behavioral circadian periods. Here, we show that these changes can be explained by a surprisingly simple mathematical relationship: the frequency is the reciprocal of the period, and its distribution becomes skewed when the period distribution is symmetric. The synchronized frequency of a population in the skewed distribution and the macroscopic frequency of combined oscillators differ, accounting for some of the atypical circadian period outputs observed in networks without synchronization. Building on this finding, we investigate the dynamics of circadian outputs in the context of aging and disease, where synchronization is weakened.

Keywords: Kuramoto model; circadian rhythms; frequency synchronization; macroscopic period; mean internal period; period distribution; period-frequency relation; unsynchronized states.

Grants and funding

This work was financially supported by the Higher Education Sprout Project of the Ministry of Education (MOE) in Taiwan. JM was supported through the National Science and Technology Council (NSTC), Taiwan (112-2314-B-038-063 and 111-2314-B-038-008). SH was supported by the Okinawa Institute of Science and Technology Graduate University. CS acknowledges support by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through grant SCHM 3362/4-1, project number 511886499. HV acknowledges support from the NSTC, Taiwan, (110-2811-B006-540, 111-2811-B006-028, and 112-2811-B006-033). M-YW acknowledges support by the NSTC, Taiwan (109-2314-B-038-106-MY3).