Overexpression Of PINN-1 In Gut Cells Prolonged The Lifespan Of Arrested L1s

Aging is a process of gradual functional deterioration at the cellular and organismal levels.With the increase of age,the body’s resistance to stress weakens,and the incidence of aging-related diseases increases.PINN-1/PIN-1 is a peptide-proline cis-trans isomerase widely expressed in various types of cells.Existing studies have shown that PIN-1 is closely related to aging-related diseases such as tumorigenesis and neurodegenerative diseases.Therefore,the study of PIN-1 signaling pathway may provide potential targets for treatment aging-related diseases.Caenorhabditis elegans(C.elegans)is a good model to study aging and stress biology due to its short life-cycle and large number of offspring.We found that under starvation,the expression of PINN-1 in the gut cells showed the most striking decrease compared to seam cells and germ cells.To explore the function of PINN-1 in the gut cells during starvation,we constructed strains overexpressing PINN-1 in the gut cells.The results showed that overexpression of PINN-1 in the gut cells significantly prolonged the survival of arrested L1 s,although it had little effect on the life span and the morphology of muscle cell mitochondria of well-fed adults.In arrested L1 s,overexpression of gut PINN-1 can also delay the mitochondrial fragmentation in muscle cells without affecting the mitochondrial morphology of gut cells.Despite heat shock and pathogen infection also reduced the expression of gut PINN-1,overexpression of gut PINN-1did not enhance resistance to heat shock and pathogen infection.Interestingly,the pinn-1 3’UTR is the key element to show the protection of gut PINN-1 under starvation,because exogenous 3’UTR linked to pinn-1 coding sequences did not promote the survival of arrested L1 s.Further studies suggested that PINN-1 overexpression in gut cells promoted survival of arrested L1 s through DAF-16/FOXO,which is a key downstream transcription factor in many classical agingrelated signaling pathway and regulates the expression of many longevity genes,such as antioxidants gene(sod-3),chaperones gene(hsp-16),metabolism-related gene(icl-1).Our findings suggest that PINN-1 is an upstream regulator of DAF-16 and may provide a novel strategy for treating aging and aging-related diseases.