Inhibition of Senescence Through Decreasing P16ink4a Expression by Sirt-1 in ADMA Exposed EPC

Titin Andri Wihastuti (), Wiwit Nurwidyaningtyas and Kumboyono Kumboyono
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Titin Andri Wihastuti: Universitas Brawijaya, Basic Nursing Department, Faculty of Health Sciences
Wiwit Nurwidyaningtyas: Sekolah Tinggi Ilmu Kesehatan Kendedes, Department Molecular and Cellular Biology
Kumboyono Kumboyono: Universitas Brawijaya, School of Nursing, Faculty of Health Sciences

A chapter in Proceedings of the 2022 Brawijaya International Conference (BIC 2022), 2023, pp 488-494 from Springer

Abstract: Abstract Senescence is associated with various degenerative diseases, such as cardiovascular disease (CVD). The community must bear the economic burden due to CVD, not only from the prohibitive medical costs but also from the decline in people’s work productivity due to suffering from CVD. Various efforts have been made to prevent premature senescence. Sirtuin-1 (SIRT-1) is essential in maintaining vascular homeostasis through the modulation of senescence-associated signaling pathways. Vascular homeostasis is highly dependent on the quality of endothelial cells as the primary vascular component. Good vascular regeneration is primarily determined by the Endothelial Progenitor Cell (EPC). Exposure to CVD risk factors is thought to trigger premature senescence of EPC. The molecular mechanism of premature EPC senescence associated with CVD is still unclear. This study aimed to test whether the specific activator of SIRT-1 could inhibit the senescence of EPCs exposed to Asymmetric Dimethylarginine (ADMA) by decreasing P16INK4a, which is one of the markers of cell senescence. True-experimental research method in vitro using EPC culture obtained from PBMNC. This study has three groups: the EPC group, the EPC group with exposure to ADMA, and the EPC group receiving SIRT-1 before exposure to ADMA. The results showed that the intensity of P16INK4a expression increased dramatically in EPCs exposed to ADMA compared to controls. In addition, the study results also showed a decrease in the expression of P16INK4a in EPCs given SIRT-1 before exposure to ADMA compared to EPCs exposed to ADMA without SIRT-1 administration. The decrease indicates the protective effect of SIRT-1 against EPC senescence due to ADMA exposure.

Keywords: atherosclerosis; senescence; EPC; SIRT-1; ADMA; P16INK4a (search for similar items in EconPapers)
Date: 2023
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DOI: 10.2991/978-94-6463-140-1_49

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