Ginsenoside Rg1Extends The Lifespan And Delays Brain Aging In C57BL/6J Mice

Object Normal aging brain is the most common cause of cognitive decline inaging individuals, and significantly reduces the quality of life by diminishing healthspan. Here we testify whether long-term administration of ginsenoside Rg1wouldextend the lifespan and improve age-related cognitive decline. In addition，we explorethe potential mechanisms using in vivo studies through animal，tissue and molecularlevels.It is a helpful exploration for anti-aging and slow brain aging via aim atdifferent crucial factors during the Rg1comprehensively intervene senescenceprogress.Methods we initiated supplementation of female C57BL/6J mice with a lowdose （6mg/kg/3day）ginsenoside Rg1or solvent at12months of age, and randomlydivided into longevity and sacrifice groups. In longevity group, mice in the longevitygroup (n=34-38in each subgroup) were allowed to die of natural causes and analyzedthe survivals. In sacrifice groups, the supplementation ended at24months.,Solvent-control mice, young (4-months-old) and middle-aged (12-momths-old) micewere used as control (n=12-16in each subgroup). The effect of brain aging and Rg1on the learning and memory of C57BL/6J mice was tested by different behavioraltests including Y maze and Morris. The aged neuron was examined by the enzymestaining and electron microscope scanning, oxidative stress in brain tissue was testedby ELISA or spectrophotometer, and the plasticity-related proteins and the mTORsignaling pathwany in hippocampus were tested by immunohistochemistry stainingand Western blot.Results1. Long-term low dose oral supplementation of Rg1increased theaverage and maximum lifespan and improve aged-related cognitive decline, withoutsignificant effects on the cancer incidence, body weight and food consumption. 2. Rg1reduce the levels of H2O2, protein carbonylation and improve SODactivity on brain tissue, so that decrease the lipofuscin accumulation and mitochondriadamage. Consequently, Rg1could enhance antioxidant ability and delay neuronalaging in aging individuals. However, senescence or Rg1did not play role on theumber of ChAT-positive neurons in the basal forebrain.3. Rg1could protect the synaptic structural degradation on aged hippocampusCA1area and significantly up-regulated synaptic plasticity associated proteins inhippocampus, including synaptophysin, NMDAR1, PSD-95and CaMKIIα, viapromoting mTOR pathway activation, then improve the cognitive function.Conclusion Rg1reduce the oxidative damage on the aged neuron throughenhance the antioxidant capacity, and up-regulate synaptic plasticity associatedproteins in hippocampus via promoting mTOR pathway activation. Rg1, that couldextend the lifespan and improve aged-related cognitive decline, is benefic for healthyof aging individuals. Consequently, Rg1may be a effective and safe effective healthmedicine for anti-aging.