Circadian system ageing in cancer: from tumourigenesis to treatment

Age is cancer's primary risk factor and a significant determinant of how the resulting disease presents andprogresses. Yet the specific contribution of ageing’s diverse hallmarks to this phenomenon is poorly defined.Circadian rhythms are a conserved adaptation that enables organisms to anticipate daily environmentalcycles and thus mitigate their harmful effects on the body. However, in recent years, a decay of homeostaticcellular, tissue and systemic circadian rhythms has emerged as a hallmark of mammalian ageing.Concurrently, in the context of cancer, circadian inputs from the host are known to drive daily rhythms intumour microenvironment composition, metastasis seeding and treatment response, whilst disruption ofphysiological circadian rhythms is itself an established tumour promoter. When considered together, thisraises the intriguing possibility that ageing of the circadian system may reshape cancer circadian biology in amanner pertinent to its prevention or treatment.In particular, three key questions emerge: 1) Does ageing of the body and its circadian rhythm system changethe tumourigenic potency of circadian rhythm disruption? 2) Are the circadian rhythms of an establishedtumour altered by ageing of the host and its circadian system? 3) If cancer circadian biology is rewired byageing, can we identify where this change originates from?In CircTu-Age, we will combine cutting-edge models of ageing and cancer with targeted circadian rhythmdisruption and circadian-omics to define how ageing impinges upon the circadian biology of cancer. Thistimely project will reveal the as-yet-uncharacterised interaction between an emerging hallmark of ageing,circadian rhythm decay, and the most common of age-related diseases, cancer. The knowledge generated byCircTu-Age will provide a roadmap for identifying interventions that diminish cancer risk later in life, andcontribute to refining and expanding the burgeoning field of cancer chronotherapy.