Anti-aging effects of glycyrrhizin via maintaining Klotho levels.

Klotho, an anti-aging protein, controls the insulin-like growth factor-1 (IGF-1) and suppresses inflammation implicated in senescence. We previously reported that glycyrrhizin (GL), a medicinal ingredient of licorice root, significantly attenuates inflammatory responses by inhibiting high-mobility group box 1 (HMGB1). In this study, we investigated whether GL is effective in suppressing the decline in Klotho levels and aging-induced frailty. After oral administration of GL three times a week for 12 months, the following effects were observed: reductions in the increases in blood fats, steatoses, obesity, and kidney aging; maintenance of activity level and rotarod test performance. Furthermore, we found beneficial effects of GL on the blood levels of functional proteins; upregulation of anti-aging factors, IGF-1 and Klotho; decrease in cystatin-C, an indicator of declining kidney function; and decreases in IL-6 and TNF-α, inflammatory cytokines. GL also seemed to increase superoxide dismutase 2, an antioxidant enzyme, in the liver and kidneys. As GL can inhibit HMGB1, it may attenuate this inflammatory amplification loop, reducing the systemic senescence-associated secretory phenotype and thus mitigating multiple aging phenotypes by maintaining Klotho levels.