Targeting the circadian clock in personalized disease prevention

Introduction

Virtually every cell of our body follows the 24-hr ‘circadian’ rhythm of a hypothalamic master pacemaker that evolved in the natural light-dark cycle. Decoding this circadian clock culminated in the Nobel Prize in Physiology or Medicine 2017 for the discovery of molecular mechanisms controlling the circadian rhythm.

Importance of Circadian Rhythm

It is now recognized that a strong, unperturbed circadian clock is a hallmark of healthy aging. The introduction of electric light, however, presents unique challenges: today, 20% of the global workforce engages in alternate working hours associated with light at unnatural times.

Health Risks Associated with Night Work

Increases in the risk of major chronic disease and mortality have been associated with night work. Further, night activity is widespread also outside of work, implicating potential risk for many.

Project Objectives

This project targets the urgency of alleviating adverse health consequences of a perturbed clock. It does so by aiming to decipher individual risk and related mechanisms through the following approaches:

1. Using a cutting-edge multi-polygenic score approach.
2. Employing transgenerational, deeply phenotyped cohort approaches.
3. Carrying out interventions using genetic risk stratification.

Background of the Research

This epidemiological project builds on pioneering work of the applicant who conducted the first prospective study to demonstrate significant health effects of chronic clock dysregulation, leading WHO to classify night work as a probable carcinogen.

Methodology

Using transdisciplinary approaches, she implemented field and genetic studies and developed circadian biomarkers, establishing the field of circadian epidemiology.

Future Directions

Tying the transformative body of her work together, she proposes to take the next groundbreaking leap:

1. Identify the night-active individual who develops disease.
2. Profile mechanisms involved.
3. Optimize the effectiveness of interventions to improve sleep and shift work disorder.

This will facilitate immediate implementation of risk-based prevention strategies aimed at promoting healthy aging in spite of clock perturbations.