Inorganic nitrate alleviates the senescence-related decline in liver function

Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals. Dietary nitrate supplements have physiological and therapeutic effects on organ function by nitrate (NO₃^-)-nitrite (NO₂^-)-nitric oxide (NO) pathway. However, the role of dietary nitrate on the senescence-related decline in liver function is unclear. The findings of the present study showed that nitrate levels in the serum and liver decreased, whereas the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum increased in ageing mice. Consistently, cell senescence, decreased glycogen levels and increased lipid deposition were found in the liver of aged mice, both glucokinase (GCK) and phosphoenolpyruvate carboxykinase (PCK) were down-regulated (n=10). Daily nitrate intake (0.5 mmol L^-1) restored nitrate levels, decreased ALT and AST levels, and prevented cell senescence and structural and glucose and lipid metabolism degeneration in liver tissue both in D-galactose (D-gal)-induced ageing mice (n=10) and in natural aged mice (n=10). In conclusion, the present study demonstrated that the reduction of nitrate levels was correlated with liver degeneration in ageing individuals and that dietary supplement of nitrate could restore the nitrate levels in serum and the liver and prevent ageing-related liver degeneration.