Leader: Daniele Gianfrilli (SAPIENZA); Other collaborator(s): Licia Iacoviello (NEUROMED); Patrizia Rovere Querini (UNISR)
Loss of circadian rhythms or clock misalignment is frequently early seen in metabolic disorders -before end-organ damage occurs- and impacts the value of traditional biomarkers. Likewise, the endogenous clock can influence the response to treatments. The task will develop a new approach integrating the 'circadian dimension' to risk stratification. Biological rhythms and chronotypes will be integrated into a multidimensional analysis of biological samples and clinical data. Milestones are 1) analysis (post-hoc) of time-sensitive profiling for the immune and endocrine systems; 2) multidimensional modeling with circadian time as a new modifier for diagnostic procedures; 3) theorization of chrono-pharmacological intervention strategies.
Brief description of the activities and of the intermediate results: Loss of circadian rhythms or clock misalignment is frequently early seen in metabolic disorders -before end-organ damage occurs- and impacts the value of traditional biomarkers. Likewise, the endogenous clock can influence the response to treatments.
A new approach integrating the 'circadian dimension' to risk stratification is under development.
Biological rhythms and chronotypes will be integrated into a multidimensional analysis of biological samples and clinical data. Milestones are 1) analysis (post-hoc) of time-sensitive profiling for the immune and endocrine systems; 2) multidimensional modelling with circadian time as a new modifier for diagnostic procedures; 3) theorization of chrono-pharmacological intervention strategies.
Main policy, industrial and scientific implications: Novel biomarker discovery related to endocrine and metabolic aspects is expected to be available for populations of older adults with multimorbidity and polypharmacy.
The research team performed a literature research for novel biomarkers of circadian rhythm disruption in aging patients. In collaboration with WP2 a protocol to explore the effects of training in Type 2 Diabetes Mellitus was drafted. A paper exploring steroid hormones and sexual function in patients with Adrenal Insufficiency in relation to circadian glucocorticoid replacement was accepted for publication by the journal Andrology (IF 4.6 doi:10.1111/andr.13635). An additional protocol in collaboration with WP2 to analyze aging epigenetic biomarkers was also finalized.
The research group started a meeting series to evaluate further steps in equipment acquisition, protocol drafting and feasibility of epigenetic analyses. Revision of published literature on the epigenetic clock was also performed. Results from the CHROnOS trials were submitted as abstract to the European Congress of Endocrinology.
Results from the CHROnOS trial, identifying immune system and clock genes expression as valuable biomarkers for chronodisruption, were presented at the European Congress of Endocrinology in the European Women in Endocrinology Symposium by Dr. Hasenmajer. The paper was also submitted for peer review.
A scientific meeting for technical proceedings of the epigenetic clock analyses was performed to evaluate sample size for both patients with glucocorticoid disorders and patients with type 2 diabetes mellitus. Enrolment of controls and ageing patients continued in the context of the emended CHROnOS trial.
Circadian analyses were integrated by individual-data examination and sex- and age- interaction analyses. The study team participated in the Spoke meeting and presented the advancements of the task-related scientific activities.
Reply to reviewers for the CHROnOS trial article was finalized and submitted.
During the last trimester of 2024, the main paper summarizing findings from the CHROnOS trial was accepted for publication and published on the prestigious journal EBiomedicine. Title of the paper was “Circadian clock disruption impairs immune oscillation in chronic endogenous hypercortisolism: a multi-level analysis from a multicentre clinical trial” (doi: 10.1016/j.ebiom.2024.105462). Results from machine learning analyses identified markers of circadian disruption in the rare model of endogenous hypercortisolism that will be potentially transferred to the ageing population.
Results from the paper were also presented at the II Edition of the “DIABENDRO” congress (4th December 2024).
Collaboration with WP2 for consulting and project advancement were continued during the last trimester of 2024.
Oral presentation of abstract “Circadian clock disruption impairs immune oscillation in chronic endogenous hypercortisolism: a multi-levels analysis from a multicentre clinical trial.” based on the findings from the CHROnOS trial at the EUWIN (European Women in Endocrinology) symposium at the European Congress of Endocrinology (13th May 2024). The abstract was selected as “outstanding abstract presented by a woman”.
Oral presentation of data on circadian rhythms in glucocorticoid disorders at the II Edition of the “DIABENDRO” congress (4th December 2024)
Publication of the paper “Circadian clock disruption impairs immune oscillation in chronic endogenous hypercortisolism: a multi-level analysis from a multicentre clinical trial” summarizing findings from the CHROnOS trial on the journal EBiomedicine vol. 110, December 2024 (doi:10.1016/j.ebiom.2024.105462)