Evening blue light attenuates melatonin‑SIRT1 axis, damping circadian amplitude and accelerating inflammaging

Hypothesis: Chronic evening exposure to blue‑light (460‑480 nm) diminishes melatonin secretion, which in turn reduces SIRT1 activity, blunts circadian amplitude, and promotes a low‑grade inflammatory state that accelerates biological aging.

Melatonin released during darkness binds MT1/MT2 receptors, triggering G‑protein signaling that raises intracellular NAD+ levels and activates SIRT1 deacetylase activity. SIRT1 then deacetylates core clock components such as BMAL1 and PER2, stabilizing their transcriptional cycles and increasing the amplitude of circadian rhythms. When evening blue light suppresses melatonin (as shown by a drop to ~7.5 pg/mL after 2‑3 h exposure)Evening blue light suppresses melatonin and delays phase, NAD+ synthesis falls, SIRT1 activity declines, and clock gene expression becomes dampened. Low amplitude reduces the segregation of anabolic and catabolic processes, leading to heightened NF‑κB signaling and inflammasome activation, which drives chronic inflammation—a key driver of inflammagingCircadian deterioration fosters inflammation and accelerates aging.

Because high sleep regularity, a proxy for strong amplitude, predicts 20‑48 % lower all‑cause mortalitySleep regularity predicts lower mortality, we hypothesize that preserving melatonin‑SIRT1 signaling by blocking evening blue light will maintain amplitude, lower inflammatory markers, and slow epigenetic aging.

Testable prediction: In a randomized crossover trial with adults aged 60‑80, participants will wear blue‑blocking glasses (λ < 480 nm) or clear control glasses from sunset to bedtime for two weeks each, separated by a washout. Primary outcomes will be salivary melatonin AUC, SIRT1 activity measured in peripheral blood mononuclear cells, circadian amplitude derived from actigraphy (interdaily stability), plasma IL‑6 and CRP, and DNAm PhenoAge acceleration. We expect the blue‑blocking condition to raise melatonin AUC by ≥30 %, increase SIRT1 activity by ≥20 %, boost amplitude (interdaily stability) by ≥10 %, reduce IL‑6/CRP by ≥15 %, and lower PhenoAge acceleration relative to control. Conversely, if melatonin, SIRT1 activity, amplitude, or inflammatory markers do not differ between conditions, the hypothesis is falsified.

A complementary arm could test whether exogenous melatonin (0.3 mg) taken 30 min before dark restores SIRT1 activity and amplitude even without glasses, providing mechanistic specificity.