Differential proteome profiling reveals curcuminoid-induced changes in metabolic and physiological pathways in aging dogs

Abstract Curcuminoid effects on aging dog proteomes remain underexplored. Plasma shotgun proteomics revealed that 135-day curcuminoid supplementation significantly altered 2,224 proteins (p < 0.05), with 1,154 differentially expressed (fold-change > 2): 582 upregulated and 572 downregulated versus baseline. Curcuminoids enhanced proteins involved in metabolism, autophagy, and repair while suppressing inflammation, calcium signaling, and coagulation factors. Notably, curcuminoids modulated JAK-STAT signaling by upregulating negative regulators PIAS2 and SOCS2, reducing pro-inflammatory complement and coagulation factors, indicating diminished inflammaging. mTOR pathway modulation featured upregulation of negative regulators including stress-inducible geroprotective SESN2, plus GRB10, SGK1, ULK1, and PRKCA. Curcuminoids rebalanced calcium signaling networks via ITPR1, CALML4, CACNA1H, STIM2, and MYLK4 regulation—essential for muscle function and neuronal health—reducing age-related dysregulation. Proteomic shifts corresponded to improved oxidative stress markers: lower plasma malondialdehyde and restored glutathione redox status. Curcuminoids enhance metabolic flexibility, proteostasis, and immune resilience, emphasizing their geroprotective potential with translational relevance to humans.