Extending The Lifespan Of Caenorhabditis Elegans Using Metal-organic Frameworks/Deuterohemin-Peptide Nanocomplex

Metal-organic frameworks(MOFs)-an emerging class of hybrid porous materials built from metal ions or clusters bridged by organic linkers.In the past ten years,MOFs have developed rapidly and has been used in many fields,such as gas storage and separation,sensing,imaging,catalysis,etc.The superior properties of MOFs,such as well-defined pore aperture,tailorable composition and struc-ture,tunable size,versatile functionality,high agent loading,and improved biocompatibility,make them promising candidates.So they have been also gradually applied in the field of biomedicine.Among them,Zr-MOF is relatively easy to synthesize and has a stable structure,named by[Zr6O4(OH)4](BDC)6(UiO-66)In this article,UiO-66 was selected to load a peroxidase mimic enzyme DhHP-6,which is a derivative of hypoheme.DhHP-6 has a stable structure.And previous studies have shown that it could be taken into the body of C.elegans and achieve a good effect of extending the life of C.elegans.An enzyme mimic harboring iron porphyrin(DhHP-6)loading into metal-organic frameworks UiO-66 was constructed through physical absorption approach to obtain the composite DhHP-6@UiO-66.The metal-organic frameworks/deuterohemin-peptide nanocomplex was then used as antioxidants to interfere with ROS and demonstrated a 55.57%lifespan-extending effect in C.elegans.More importantly,DhHP-6@UiO-66 could efficiently reduce the accumulation of lipid deposits by 18.74%in N2 and lengthened the healthspan of C.elegans.In addition,DhHP-6@UiO-66 exhibited the ability to extend the longevity of wild-type C.elegans during heated stress and oxidative stress.To explore the possible mechanisms,in this study we investigated the roles of daf-2,daf-16,skn-1,sod-3 and hsp-16.2 in the regulation of their life expectancy in wild-type C.elegans DhHP-6@UiO-66 significantly down-regulated the expression of daf-2 and up-regulated the expression of daf-16,sod-3,skn-1 and hsp-16.2 and provide new insights into the molecular mechanisms of aging.Thus,this MOF NPs can be potentially used as an effective antioxidant to extend the average life expectancy by providing environmental pressure protection.