Loss Of Bmal1 Leads To Dysfunction Of Salivary Gland Secretion

This study investigates how circadian disruption (particularly aging/sleep disorders) impairs salivary secretion, focusing on BMAL1 knockout mechanisms to identify therapeutic targets for gland dysfunction. Using BMAL1-knockout rats (3-/12-month-old WT/KO), we assessed salivary flow rates, histopathology, apoptosis (TUNEL), and antimicrobial protein expression (lysozyme/lactoferrin). ChIP-seq profiling identified BMAL1-regulated pathways in glandular epithelia. BMAL1 deficiency induces gland dysfunction characterized by xerostomia, with age-dependent salivary flow reduction and absence of Sjögren-like lymphocytic infiltration. Despite reduced lactoferrin/lysozyme expression, their intracellular accumulation was observed. BMAL1-knockout glands exhibited vacuolar degeneration (particularly lacrimal) and increased apoptosis, alongside mild inflammation without T/B-cell/macrophage infiltration. ChIP-seq revealed BMAL1′s enrichment in salivary secretion pathways (KEGG analysis), indicating direct regulation of secretory mechanisms. BMAL1 maintains salivary homeostasis by regulating secretory machinery and preventing acinar degeneration. Chronodisruption-induced BMAL1 deficiency drives gland dysfunction through apoptosis and calcium dysregulation. Targeting BMAL1 signaling offers chronotherapeutic potential for age-related xerostomia.