LRRK2^R1627P mutation in rats accelerates dopaminergic neuronal senescence in an age-dependent manner. The mechanism involves the R1627P mutation disrupting the Golgi structure by inhibiting Rab10 phosphorylation, which in turn impairs the Golgi-lysosome signaling pathway in dopaminergic neurons, accelerating cellular senescence. Moreover, genetic factor (LRRK2^R1627P mutation) is more likely to exacerbate intestinal inflammation and pathological α-synuclein aggregation in the rat, when combined with environmental factor (LPS exposure). This pathological phenomenon can spread through the gut-brain axis, leading to microglial activation and the expression of pathological α-synuclein in the brain.