PhD Scientific Days 2026

Molecular Medicine 2.

The Circadian Rhythm Across the Body: Comparison of the Central and Peripheral Clock Functions

Name of the presenter

Lumniczky, Zalán

Institute/workplace of the presenter

Department of Physiology Semmelweis University

Authors

Zalán Lumniczky¹, Bianka Farkas¹, Csongor György Szántó¹, Krisztina Ella¹, Krisztina Káldi¹
1: Department of Physiology Semmelweis University

Text of the abstract

Introduction: Circadian rhythm enables organisms to anticipate and adapt to the rhythmic changes of the environment. In mammals, circadian rhythm coordination is organized hierarchically. The central pacemaker in the suprachiasmatic nucleus is well characterized at both the cellular and molecular levels. Although molecular components of the circadian clock have also been identified in several peripheral tissues, the functional significance of many peripheral oscillators remains unclear. Communication mechanisms between peripheral oscillators and the central clock are not fully understood, and alignment among peripheral clocks is completely unexplored. However, assessing the phase of tissue-specific rhythmic functions may be critical for effective chronotherapy.
Aims: The aim of this study was to investigate the relationship between the central clock and two peripheral clocks – peripheral blood mononuclear cells (PBMCs) and buccal mucosa (BM) – in humans.
Methods: Blood and buccal mucosa samples were collected from 12 healthy subjects at six time points over a 24-hour period. Leukocyte populations and plasma cortisol levels were measured, and RNA was isolated from PBMCs and BM. Clock gene expression (PER2, REV-ERBα, DBP) was analyzed using RT-PCR. Core body temperature (CBT) was continuously monitored using CALERA Research, and chronotype was assessed using the Munich Chronotype Questionnaire. Statistical analysis was performed in R.
Results: Significant daily oscillations of REV-ERBα and DBP were observed in both peripheral tissues. Leukocyte subpopulations, plasma cortisol levels, and CBT also exhibited rhythmic changes. Surprisingly, individual-level comparisons revealed antiphasic clock gene oscillations between PBMCs and BM. While peripheral clock acrophases showed marked interindividual variability, rhythm parameters influenced by the master clock were more consistent.
Conclusion: Our data suggest that social constraints may strongly shape the phase of the master clock. Clock gene expression in peripheral tissues shows tissue-specific phases and marked interindividual variability. These insights may serve as important considerations in the planning of chronotherapy.
Funding: OTKA (132393), TKP-EGA-25, ÚNKP-23-5-SE-20, János Bolyai Research Scholarship, EKÖP-2025-695, EKÖP-2024-175