The Vicious Cycle of Sleep Disruption and Inflammaging: Mechanisms, Consequences, and Therapeutic Opportunities

ABSTRACT

Aging is characterized by two interdependent hallmarks: a chronic low‐grade inflammatory state known as inflammaging, and a progressive deterioration of sleep and circadian rhythms. Emerging evidence indicates that these are not merely parallel processes but are mechanistically intertwined in a self‐perpetuating cycle. This review synthesizes current knowledge on how age‐related sleep and circadian disturbances exacerbate inflammaging through distinct molecular and cellular pathways. We examine the nocturnal dysregulation of the immune system, focusing on innate immune hyperactivation (e.g., via NLRP3 inflammasome and TLR4 signaling), cellular senescence (SASP), adaptive immune decline (T‐cell aging), and disruption of systemic pathways such as the gut‐brain axis. Clinical and epidemiological data link sleep disorders, particularly obstructive sleep apnea, to elevated inflammatory markers, accelerated epigenetic aging, and cognitive decline. Conversely, inflammaging impairs circadian regulatory structures, further degrading sleep quality. Interventions targeting the sleep‐immune axis, including melatonin, circadian reinforcement, senotherapeutics, and lifestyle modifications, hold promise for mitigating inflammaging. We conclude that sleep disruption is not a passive symptom but an active driver of immunological aging, and propose that targeting this axis represents a viable strategy for promoting healthy longevity.