Role of phospholipase D in the lifespan of Caenorhabditis elegans

We have previously shown that phospholipase D (PLD) downregulation accelerates cellular senescence(definition), 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 protein phospholipase D (PLD) is involved in preventing the appearance of signs of aging and prolonging lifespan. Reactive oxygen species (ROS) are a normal byproduct of metabolism, but they can damage cells and DNA, and their accumulation is associated with aging. ROS can be removed by antioxidants, and this removal may promote longevity. Young-Seuk Bae at Kyungpook National University, Daegu, South Korea and co-workers investigated the role of phospholipase D (PLD), a protein previously linked to cellular senescence, in a worm used as a model organism. Individuals without PLD showed increased ROS accumulation, decreased motility and resistance to stress, and a shorter lifespan. Deletion of PLD decreased expression of antioxidant genes. The researchers conclude that deleting PLD reduced expression of antioxidant genes, which increased ROS accumulation, promoting signs of aging and shortening lifespan.