Sanghuangporus Sanghuang Extract Extended The Lifespan And Healthspan Of Caenorhabditis Elegans Via DAF-16/SIR-2.1

Aging is a gradual decline and weakening of human body functions,which typically leads to reduced physical and cognitive capabilities and increased incidence of various diseases.Slowing down aging and extending healthy lifespan is an urgent issue that needs to be addressed in modern society.Currently,there are various drugs that can be used to treat aging,such as the most common rapamycin,metformin,and some other drugs,but they can only delay the aging process to a certain extent and are accompanied by side effects such as diarrhea,nausea,and abdominal pain.Therefore,people urgently need to find a safe and effective method to delay aging.Sanghuangporus sanghuang,a traditional Chinese medicine,has been described in the"Shennong’s Classic of Materia Medica"from the Han dynasty as having the effects of clearing heat and toxins,promoting blood circulation and removing blood stasis.In modern medicine,Sanghuang is widely recognized for its anti-tumor and anti-inflammatory properties and has been approved for use as an adjunctive therapy in some countries and regions.However,whether Sanghuangporus sanghuang has anti-aging effects has not been thoroughly investigated,and its mechanisms of action remain unknown.In this study,we used the model organism Caenorhsaaabsditis elegans（C.elegans）to investigate the anti-aging effects of Sanghuangporus sanghuang Extract（SSE）and further analyze its possible mechanisms of action.The specific research contents are as follows:（1）We observed the effect of different concentrations of SSE on the survival rate of wild-type C.elegans（N₂）in a lifespan assay.We found that SSE extended both the mean and maximum lifespan of the worms.Especially,the worms treated with 25mg/m L SSE showed a 26.41%increase in mean lifespan compared to the control group.（2）We observed the effects of SSE treatment on various physiological indicators of the worms that are related to healthy lifespan,including reproductive ability,body length,movement speed,thrashing ability,and pharyngeal pumping rate.We found that SSE improved the movement speed and thrashing ability of the worms without affecting their reproductive ability,body length,and pharyngeal pumping rate.（3）We measured the levels of lipofuscin,reactive oxygen species（ROS）,and fat accumulation in the worms.The results showed that SSE treatment significantly reduced the levels of lipofuscin,ROS,and fat accumulation in the worms.（4）Through heat stress and oxidative stress experiments,it was found that worms fed with SSE could resist the damage to their bodies from heat and oxidative environments for a longer period of time,and could survive longer under adverse conditions.SSE treatment improved the stress resistance of the worms.（5）Real-time fluorescent quantitative PCR（RT-q PCR）results showed that the expression levels of daf-16 and sir-2.1 in worms treated with SSE significantly increased.The expression of genes related to heat stress and oxidative stress,such as sod-3 and hsp-16.2,also increased.SSE may delay worm aging by regulating the expression levels of daf-16 and sir-2.1 through the insulin/IGF-1 signaling pathway.（6）Metabolomics analysis showed that SSE treatment caused significant changes in the levels of amino acid metabolism in the worms,and the increase in branched-chain amino acids,including leucine,could activate the expression of sir-2.1 and thereby delay aging.In summary,this study demonstrated that SSE can extend the lifespan and healthy lifespan of C.elegans,and its mechanism of action may involve upregulating the expression of daf-16 and sir-2.1 on the insulin/IGF-1 signaling pathway,as well as changes in amino acid metabolism.