Role of phospholipase D in the lifespan of Caenorhabditis elegans

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Title
Role of phospholipase D in the lifespan of Caenorhabditis elegans
Author(s)
Jeong-Hwan Park; Jeong-Woo Park; Ju-Hyeon Lee; Dong-Yun Kim; Jeong-Hoon Hahm; Young-Seuk Bae
Publication Date
2018-04
Journal
EXPERIMENTAL AND MOLECULAR MEDICINE, v.50, no., pp.8 -
Publisher
NATURE PUBLISHING GROUP
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. © 2018 The Author(s)
URI
https://pr.ibs.re.kr/handle/8788114/5788
ISSN
1226-3613
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
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