AgingSep 17, 2026

Reducing the enzyme Pla2g15 lowers certain fat molecules and aging signs in kidney cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 18, 2026

Abstract

Lysosomal phospholipid metabolism is implicated in the senescence of proximal tubular epithelial cells, with BMP levels increasing during kidney aging.

Chronic kidney disease is associated with the accumulation of senescent proximal tubular epithelial cells, which leads to fibrosis and functional decline.
The lysosomal phospholipid bis(monoacylglycerol)phosphate (BMP) was found to increase in senescent tubular epithelial cells and during kidney aging.
Genetic knockout of the BMP hydrolase Pla2g15 in tubular epithelial cells resulted in elevated levels of total lysophosphatidylglycerol and BMP.
Long-chain unsaturated BMPs decreased in Pla2g15-deficient cells, while wild-type cells showed increased BMP levels upon induction of senescence.
Knockout of Pla2g15 offered protection against senescence induced by doxorubicin, linked to enhanced mitochondrial metabolism and fatty acid oxidation.
These findings suggest that targeting PLA2G15 could be a potential strategy to combat senescence and slow the progression of chronic kidney disease.

Simplified

Chronic kidney disease (CKD), a major age-related pathology, is driven by the accumulation of chronic senescent proximal tubular epithelial cells (TECs), promoting fibrosis and functional decline. Although senescence involves metabolic reprogramming, the role of complex lipid metabolism in TECs senescence remains poorly understood. Here, we identify a critical role for lysosomal phospholipid metabolism in senescent TECs. We show that the lysosomal phospholipid bis(monoacylglycerol)phosphate (BMP) increases during kidney aging and in senescent TECs. Genetic knockout of the BMP hydrolase Pla2g15 in TECs elevated total lysophosphatidylglycerol (LPG) and BMP, with a notable shift in BMP species. Long-chain unsaturated BMPs, which accumulate during doxorubicin-induced senescence in TECs, were specifically reduced in Pla2g15-deficient cells, whereas wild-type TECs showed increased levels upon senescence induction. Pla2g15 knockout also provided significant protection against doxorubicin-induced senescence. Proteomic profiling revealed that this protection was linked to enhanced mitochondrial metabolism, including NAD+ metabolism and fatty acid oxidation. These findings demonstrate that PLA2G15 contributes to TEC senescence through selective BMP lipid remodelling and regulation of mitochondrial function. Targeting PLA2G15 therefore may represent a promising therapeutic strategy to prevent senescence and the associated burden of CKD progression.

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Reducing the enzyme Pla2g15 lowers certain fat molecules and aging signs in kidney cells

Abstract

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