Inorganic nitrate alleviates the senescence-related decline in liver function
Haifeng Wang;Lei Hu;Le Li;Xiaoshan Wu;Zhipeng Fan;Chunmei Zhang;Jinsong Wang;Jidong Jia;Songlin Wang;Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology;Department of Stomatology, Beijing Bo'ai Hospital, China Rehabilitation Research Center, School of Rehabilitation, Capital Medical University;Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,School of Stomatology, Capital Medical University;Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences;Liver Research Center, Beijing Friendship Hospital, Capital Medical University;
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(NO_3~-)-nitrite(NO_2~-)-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.
【Fund】： supported by the National Natural Science Foundation of China (91649124);; Beijing Municipality Government grants (Beijing Scholar Program- PXM2016_014226_000034 PXM2016_014226_000006 PXM2015_014226_000116 PXM2015_ 014226_000055 PXM2015_014226_000052 PXM2014_014226_000048 PXM2014_014226_000013 PXM2014_014226_000053 Z121100005212004 PXM2013_014226_000055 PXM2013_014226_000021 PXM 2013_014226_07_000080 TJSHG201310025005)
【CateGory Index】： R575
【CateGory Index】： R575