Biological Rhythm Research · Aug 18, 2026
Dynamic integration of metabolic, circadian and neuroendocrine axes in ageing and regeneration from the cellular and molecular perspectives
By Salma U, Islam MM, Islam MM et al.
Ageing is a dynamic process marked by declining physiological integrity and increasing susceptibility to chronic disease. This review synthesizes current evidence and proposes an integrative systems biology framework in which dietary restriction, circadian rhythms and neuroendocrine stress regulation function as three interconnected regulatory axes that coordinate dynamic transitions between repair-dominant and growth-dominant cellular states. Specifically, dietary restriction induces metabolic reprogramming through modulation of mTOR, AMPK and sirtuin signalling, thereby enhancing autophagy, mitochondrial function and epigenetic regulation, while circadian rhythms provide the temporal organization required to synchronize metabolism, DNA repair and stem cell dynamics. In parallel, stress responses governed by the hypothalamic–pituitary–adrenal axis promote adaptive resilience under acute conditions but accelerate biological ageing when chronically activated. Emerging mechanisms, including endoplasmic reticulum stress, cGAS-STING signalling and context-dependent inflammatory mediators, such as interleukin-6, further illustrate the molecular convergence of these pathways. Disruption of this integrated regulatory network promotes inflammaging, stem cell exhaustion and impaired tissue regeneration, whereas coordinated optimization of diet, circadian alignment and stress management enhances cellular resilience and regenerative capacity. This framework supports the concept of temporal precision lifestyle medicine and provides a foundation for developing personalized interventions to extend healthspan and reduce the burden of age-related diseases.