| The lifespan of an organism is strongly influenced by environmental factors(including diet),and internal factors(especially reproductive status).Lipid metabolism is essential for adaptation to external conditions or reproduction.Interestingly,the specific lipid distribution is associated with longevity,with increased uptake of certain lipids extending C.elegans lifespan and ameliorating human disease phenotypes.Considering lipid metabolism,excess adiposity with increased lipotoxicity leads to various age-related diseases,including cardiovascular disease,cancer,arthritis,type 2 diabetes,and Alzheimer’s disease.However,the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging.With advances in genetic engineering techniques,recent studies have demonstrated that changes in lipid metabolism are associated with aging and agerelated diseases.How lipids influence lifespan and how lipid metabolism is regulated during ageing are only beginning to be unraveled.Cinnamaldehyde(CA)is a widely used small molecule compound,and current studies on cinnamaldehyde mainly involve Drosophila,mice as well as mammalian cells,and its physiopathological effects on nematodes have not been investigated.Commonly found in nature,mainly trans cinnamaldehyde(t-CA),and widely used in industry as well as daily life is also t-CA,so in this paper,t-CA is selected to explore its effect on lipid metabolism and aging in C.elegans.First,we explored the effect of available concentrations of t-CA on longevity in wild-type C.elegans,using a lifespan assay and found no significant effect.Then by oil red staining,it was found that 20 μM concentration of t-CA significantly reduced abdominal fat accumulation in C.elegans,indicating that t-CA can regulate fat metabolism in C.elegans.We then developed a nematode model of high-fat accumulation by feeding glucose and found that t-CA could largely alleviate lipid accumulation in the nematodes fed a high sugar diet,while alleviating the toxic effects of high sugar diet.And demonstrated that 20 μM t-CA completely eliminated toxic effects caused by high sugar diet and was the optimal dosing concentration.By designing swimming experiments,egg laying statistics and chemotaxis experiments,it was found that 20μM t-CA does not significantly affect egg laying and motility in C.elegans,but show the negative chemotaxis to the C.elegans.To explore the possible mechanism by which t-CA affects lipid metabolism in C.elegans,q PCR experiments and some mutant oil red staining experiments were designed.It was found that t-CA alleviates fat accumulation by regulating the genes pod-2、mdt-15、pod-2、elo-2、fat-5、fat-6、fat-7 which are involved in lipid synthesis;Genes involved in lipolysis:aak-2、nhr-49、acs-2、lipl-4、daf-16;And the genes involved in the lipid storage sbp-1,daf-2;act in concert to maintain homeostasis of body fat metabolism in C.elegans.To explore the possible mechanism by which t-ca affects aging in C.elegans,the mutant strain was initially validated by designing a lifespan experiment.Found that tCA may depend on sbp-1、daf-16、aak-2 to synergistically regulate aging in C.elegans.t-CA was also found to scavenge excessive ROS in vivo.And suggested the possible mechanism of t-CA regulating lipid metabolism and aging in C.elegans: t-CA enhanced antioxidant capacity in nematodes,reduced ROS levels,triggered adaptive responses,and activated AMPK.Then AMPK acts on DAF-16 and SREBP transcription factors to regulate downstream fatty acid synthesis,consumption,and storage,ultimately modulating the balance of lipid metabolism in C.elegans,thereby affecting C.elegans aging.In this paper,we investigated the effect of t-ca on reducing lipid accumulation and on aging in C.elegans,and the possible mechanisms were initially explored to provide new insights into the relationship between lipid metabolism and aging,as well as new environmental influencing factors and chemical intervention methods to delay aging. |
PDF Full Text Request