Niclosamide demonstrates six interconnected mechanisms that address inflammaging—the chronic low-grade inflammation driving age-related decline. The drug performs mild mitochondrial uncoupling to reduce oxidative stress, inhibits mTORC1 while activating AMPK, restores cellular cleanup through autophagy, eliminates senescent cells while suppressing their inflammatory signals, blocks tissue-damaging Wnt signaling, and rebalances immune function. New formulations achieve therapeutically relevant plasma concentrations of 0.5-3 µmol/L, overcoming historical absorption limitations. This polypharmacological approach represents a paradigm shift in anti-aging intervention. Most geroprotective compounds target single pathways—rapamycin for mTOR, metformin for AMPK, or senolytics for cellular clearance. Niclosamide's simultaneous engagement of inflammation, metabolism, cellular maintenance, and immune function mirrors the interconnected nature of aging biology itself. The decades-long safety record as an FDA-approved anthelmintic provides a significant translational advantage over novel compounds requiring extensive safety testing. However, this remains mechanistic evidence requiring human validation. The immediate need for randomized trials using biomarkers of biological age and frailty could determine whether this repurposed drug becomes a cornerstone of preventive aging medicine.