Anemonin ameliorates human diploid fibroblasts 2BS and IMR90 cell senescence by PARP1-NAD+-SIRT1 signaling pathway

Abstract

Objective: Aging becomes the most predominant risk factor for all age-associated pathological conditions with the increase of life expectancy and the aggravation of social aging. Slowing down the speed of aging is considered an effective way to improve health, but so far, effective anti-aging methods are relatively lacking.

Methods: Anemonin (ANE) was screened from eight existing small-molecule compounds by cell viability assay. The function of ANE was determined by the analysis of cell proliferation, β -galactosidase (SA-β -Gal) activity, cell cycle, SASP secretion, NAD⁺/NADH ratio, and other aging-related indicators. The targets of ANE were predicted by Drug Target Prediction System (DTPS) and Swiss Targe Prediction System. The effect of ANE on PARP-1-NAD⁺-SIRT1 signaling pathway was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot, PARP1, NAD⁺ and SIRT1 activity detection.

Results: ANE can delay cell senescence; PARP1 is one of the targets of ANE and plays a crucial role in ANE anti-aging; ANE release more NAD⁺ by inhibiting PARP1 activity, thereby conversely promoting the function of SIRT1 and delay cell senescence.

Conclusions: Our study indicates that ANE can delay cellular senescence through the PARP1-NAD⁺-SIRT1 signaling pathway, which may be considered as an effective anti-aging strategy.

Keywords: Aging; Anemonin; NAD(+); PARP1; SIRT1.