Journal
EXPERIMENTAL GERONTOLOGY
Volume 151, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2021.111406
Keywords
Sargahydroquinoic acid; Senescence; Akt; mTOR; Endothelial cells
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2019R1I1A3A0105969012]
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Sargahydroquinoic acid can delay cellular senescence by inhibiting the Akt/mTOR signaling pathway, potentially useful for developing anti-aging therapy.
Aim: The effects of sargahydroquinoic acid (SHQA) on cellular senescence and the underlying mechanisms were investigated using human umbilical vascular endothelial cells (HUVECs). Methods: SHQA or DMSO was supplemented into the medium. Low dose of H2O2 was used to induce premature senescence. Replicative senescence was achieved by continuously culturing cells until they reached a plateau phase. Senescence biomarkers, including p53, p21, and p16 proteins, and SA-beta-Gal activity were measured. Results: Pretreatment of SHQA significantly suppressed the oxidative stress-induced protein expression of p53, p21, and p16, as well as the activity of SA-beta-Gal. Additionally, SHQA also delayed the replicative senescence as indicated by an increased population doubling number, reduced protein expression of p53, p21, and p16, as well as a decreased SA-beta-Gal activity. SHQA inhibited the phosphorylation of Akt, mTOR, and downstream targets of mTOR, such as p-S6K, which was elevated by premature senescence and replicative senescence. In the absence of senescence stimuli, SHQA also inhibited the Akt/mTOR signaling pathway and promoted autophagy. Conclusions: SHQA suppressed senescence induced by oxidative stress and replication through inhibiting the Akt/ mTOR pathway. With the potential of acting as an Akt/mTOR inhibitor, SHQA might be useful for developing anti-ageing therapy.
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