Gal-dMor-Gem

C57BL/6J mice (Dox-induced systemic senescence model)^[1]

0.2 mg/kg; 0.5 mg/kg; 1.0 mg/kg

i.p.; once weekly; 3 doses

Increased body weight in treated senescent mice relative to untreated controls; achieved 14.6% body weight increase at 0.5 mg/kg and 17.8% body weight increase at 1.0 mg/kg relative to day 10.
Improved liver (ALT, AST) and kidney (CREA, UREA) function markers across all doses, with greater restorative effects than the reference compound at 0.5 mg/kg.
Reduced lung SA-β-gal-positive cells from 62.4% to 44.2% at 0.2 mg/kg, to 16.9% at 0.5 mg/kg, and to 9.9% at 1.0 mg/kg (approaching healthy levels of 6.0%).
Increased lung LMNB1-positive nuclei from 43.9% to 57.6% at 0.2 mg/kg, to 74.9% at 0.5 mg/kg, and to 82.0% at 1.0 mg/kg (approaching healthy levels of 86.0%).
Reduced lung relative IL-6 fluorescence intensity from 1450.5 to 1205.0 at 0.2 mg/kg, to 678.1 at 0.5 mg/kg, and to 450.0 at 1.0 mg/kg.
Reduced liver SA-β-gal-positive cells from 88.1% to 63.7% at 0.2 mg/kg, to 21.7% at 0.5 mg/kg, and to 13.2% at 1.0 mg/kg (approaching healthy levels of 6.9%).
Reduced liver relative p21 expression from 0.93 to 0.78 at 0.2 mg/kg, to 0.58 at 0.5 mg/kg, and to 0.50 at 1.0 mg/kg.
Reduced liver relative p53 expression to 0.49 at 0.5 mg/kg and to 0.43 at 1.0 mg/kg (approaching healthy levels of 0.38).
Reduced SA-β-gal-positive cells, increased LMNB1-positive nuclei, and reduced IL-6 levels in heart and kidney across all doses, with greater effects than the reference compound at 0.5 mg/kg; restored these markers to near healthy levels at 1.0 mg/kg.