Chronobiology of Aging: Interactions Between Circadian Rhythms, Oxidative Stress, and Inflammation.

Abstract

Chronodisruption is increasingly recognised as a fundamental driver of biological aging rather than merely a consequence of advancing age. Although substantial evidence links circadian dysfunction with individual age-related diseases, the mechanistic integration of chronodisruption across the hallmarks of aging and its therapeutic implications remains fragmented. This review provides a comprehensive synthesis of current evidence describing how age-associated deterioration of the circadian timing system interacts with established hallmarks of aging, including genomic instability, epigenetic alterations, mitochondrial dysfunction, dysregulated nutrient sensing, impaired proteostasis, chronic inflammation, and cellular senescence. This article also incorporates how these interconnected mechanisms contribute to the development and progression of major age-related disorders, including neurodegenerative, cardiovascular, metabolic diseases, and cancer, highlighting shared molecular regulators such as BMAL1, CLOCK, PER, CRY, REV-ERBs, SIRT1, AMPK, and mTOR. Although several reviews exist that focus on individual diseases or isolated circadian mechanisms, this review integrates molecular, cellular, and translational evidence into a unified framework linking chronodisruption to systemic aging. This article discusses emerging chronotherapeutic strategies including chrono-phototherapy, chrono-nutrition, chrono-exercise, natural chrono-modulators, chrono-pharmacology, and precision geromedicine that aim to restore circadian homeostasis and improve healthy aging. Collectively, this review identifies circadian rhythm restoration as a promising systems-level therapeutic approach and outlines future directions for integrating chronobiology into precision interventions for age-related diseases.

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