The Effect Of Epigenetic Factors On Temperature Mediated Longevity Modulation

The lifespan of C.elegans can be regulated by both genetic and non-genetic factors.A large number of studies have reported the regulatory mechanisms of non-genetic factors on C.elegans lifespan,such as diet and temperature.In recent years,there have been many progresses of the regulation effects of temperature on C.elegans lifespan.For example,the temperature-sensitive neuron AFD,the temperature-sensitive ion channel TRPA-1,along with some proteins and transcription factors have been found to regulate worm lifespan in a temperature dependent manner,but the mechanistical basis is largely unknown.It was known that many environmental factors could regulate changes in epigenetic marks,and environmental factors are also non-genetic factors that can have an important impact on the C.elegans lifespan.Recent studies have found that some important environmental factors,such as diet and temperature,can regulate changes in many epigenetic modifications,which raised a question: Is there any relationship between temperature,epigenetic factors and C.elegans lifespan? Could temperature regulate C.elegans lifespan through an epigenetic pathway?To test this idea,we examined the lifespan of several epigenetic mutant worms and established a low-temperature model of RBR-2 and WDR-5.1,in which lifespan of RBR-2 deletion mutant can be extended at 15?,but on the contrary,loss of WDR-5.1 will shorten the C.elegans lifespan at 15?.In addition,we demonstrate that under long-term low-temperature conditions,there is a trans-generation effect in rbr-2(tm1231)mutant worms.Therefore,RBR-2 mutants exhibit some epigenetic properties but WDR-5.1 mutants not,which indicates that the lifespan regulation mechanism of WDR-5.1 deletion mutants is different from that of RBR-2 deletion mutants.To further explore how RBR-2 and WDR-5.1 modulate C.elegans lifespan at low temperature,we tested other member factors of the known epigenetic modification complex,but no one has a similar phenomenon to rbr-2(tm1231)or wdr-5.1(ok1417).In addition,we also explored the connection between the classical pathways of C.elegans lifespan-regulation and epigenetic factors regulate C.elegans lifespan at low temperature.We found that transcription factors daf-16 did not participate in the process of C.elegans lifespan regulation by epigenetic factors in a temperature dependent manner.To sum up,our project revealed that RBR-2 and WDR-5.1 have different effects on the C.elegans lifespan at different temperatures,and there is a transgenerational effect in the regulation of C.elegans lifespan by RBR-2 mutants.But in the research of the mechanism of RBR-2 and WDR-5.1 deletion mutants affect C.elegans lifespan,although we excluded the role of a part of epigenetic modification complex factor and transcription factor daf-16,its internal mechanism has not yet been revealed.So,we used RNA-seq and collected three replications of RBR-2 and WDR-5.1 mutants cultured at three different temperatures in order to get more information.