Abstract
Lactobacillus johnsonii JNU3402 (LJ3402) has previously been reported to ameliorate diet-induced hepatic steatosis. Because aging is tightly linked to metabolic disease, we hypothesized that LJ3402 might protect against age-related metabolic abnormalities in the liver. This study presents data demonstrating that LJ3402 administration reduces hepatic dysfunction in 24-month-old mice alongside the alleviation of general aging phenotypes. Furthermore, LJ3402 increased hepatic expression of genes involved in mitochondrial function and decreased senescence markers, thereby limiting age-related mitochondrial dysfunction and hepatocyte senescence, contributing to the attenuation of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Mechanistically, LJ3402 enhanced sirtuin 1 (SIRT1) expression in AML12 hepatocytes by stimulating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) coactivation of peroxisome proliferator-activated receptor alpha (PPARα). Consequently, SIRT1 suppressed p53 acetylation and activity in senescent AML12 cells, reducing senescence markers and mitochondrial dysfunction. Thus, LJ3402 suppresses mitochondrial dysfunction and senescence of hepatocytes by stimulating the PGC-1α-SIRT1-p53 pathway, reducing age-related hepatic lipid accumulation.