Role of phospholipase D in the lifespan of Caenorhabditis elegans

Abstract

We have previously shown that phospholipase D (PLD) downregulation accelerates cellular senescence, which is widely believed to play an important role in aging, by stimulating reactive oxygen species (ROS) accumulation in human cells. In this study, we examined the role of PLD in aging using the nematode Caenorhabditis elegans. The mRNA level of pld-1 was found to be inversely correlated with aging. RNAi-mediated knockdown of pld-1 expression in nematodes enhanced ROS and lipofuscin accumulation and decreased lifespan, motility, and resistance to stress compared to that in nematodes treated with control RNAi. Pld-1 knockdown repressed the long lifespan of age-1 and akt-1 mutants but did not further reduce the short lifespan of daf-16 mutants, suggesting that PLD functions between AKT-1 and DAF-16. The ROS scavenger N-acetyl-L-cysteine, a PLD effector phosphatidic acid and a possible CK2 activator spermidine attenuated the lifespan shortening and age-related biomarkers triggered by pld-1 knockdown. Pld-1 RNAi downregulated the expression of DAF-16 target genes such as sod-3, dod-11, and mtl-1 in nematodes. In human cells, furthermore, PLD2 downregulation decreased the transcription of FoxO3a target genes (Cu/ZnSOD, MnSOD, catalase, thioredoxin-2, and peroxiredoxin-5), whereas ectopic PLD2 expression elevated the mRNA levels of these antioxidant genes. Taken together, these results indicated that PLD downregulation shortens longevity and induces age-related biomarkers through ROS accumulation by inhibiting the DAF-16/FoxO3a pathway in nematodes.

The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

“…Bowhead whales and naked mole rats, two animals characterized by exceptional longevity, both exhibit unique phospholipid profiles (Borchman et al, ; Mitchell et al, ). The disruption of lipid hydrolases that regulate phospholipid metabolism has also been shown to decrease lifespan in worms (Park et al, ), flies (Kinghorn et al, ; Kunduri et al, ), and mice (Shinzawa et al, ). Conversely, treatment with phosphatidylcholine prolongs life in C. elegans under conditions of oxidative stress (Kim et al, ).…”

Promotion of cell autophagy and apoptosis in cervical cancer by inhibition of long noncoding RNA LINC00511 via transcription factor RXRA‐regulated PLD1

“…We also discovered that LINC00511 promotes the expression of the phospholipase D1 (PLD1) gene by increasing transcription process. PLD1 refers to phospholipase, which is enriched in neurons and pharyngeal muscles but is relatively absent in muscle and epithelial cells (Park et al, 2018). A previous study discussed that targeting PLD1 sensitizes cervical cancer by modulating LKB1 (Kang et al, 2016).…”

Molecular Effects of Silver Nanoparticles on Monogenean Parasites: Lessons from Caenorhabditis elegans

“…Likewise, the phospholipase D gene pdl-1 was up-regulated by a 3.51 z-score, and it is also involved in the DAF-16 pathway. Park et al [ 40 ] observed that pdl-1 down-regulation causes ROS accumulation and decreases longevity. Thus, the increased expression of pdl-1 may indicate a damage response by Cichlidogyrus parasites.…”