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探讨白藜芦醇抗间充质基质细胞衰老作用的生物分子机制:衰老治疗的新候选药物?

Biomolecular Evaluation of Piceatannol's Effects in Counteracting the Senescence of Mesenchymal Stromal Cells: A New Candidate for Senotherapeutics?

机构信息

Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

ASL Napoli 1 Centro P.S.I. Napoli Est-Barra, 80147 Naples, Italy.

出版信息

Int J Mol Sci. 2021 Oct 27;22(21):11619. doi: 10.3390/ijms222111619.

DOI:10.3390/ijms222111619
PMID:34769049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8583715/
Abstract

Several investigations on senescence and its causative role in aging have underscored the importance of developing senotherapeutics, a field focused on killing senescent cells and/or preventing their accumulation within tissues. Using polyphenols in counteracting senescence may facilitate the development of senotherapeutics given their presence in the human diet, their confirmed tolerability and absence of severe side effects, and their role in preventing senescence and inducing the death of senescent cells. Against that background, we evaluated the effect of piceatannol, a natural polyphenol, on the senescence of mesenchymal stromal cells (MSCs), which play a key role in the body's homeostasis. Among our results, piceatannol reduced the number of senescent cells both after genotoxic stress that induced acute senescence and in senescent replicative cultures. Such senotherapeutics activity, moreover, promoted the recovery of cell proliferation and the stemness properties of MSCs. Altogether, our findings demonstrate piceatannol's effectiveness in counteracting senescence by targeting its associated pathways and detecting and affecting P53-dependent and P53-independent senescence. Our study thus suggests that, given piceatannol's various mechanisms to accomplish its pleiotropic activities, it may be able to counteract any senescent phenotypes.

摘要

几项关于衰老及其在衰老中的因果作用的研究强调了开发衰老疗法的重要性,衰老疗法专注于杀死衰老细胞和/或防止它们在组织中积累。鉴于多酚类化合物存在于人类饮食中,已证实其具有耐受性且无严重副作用,并且它们在预防衰老和诱导衰老细胞死亡方面发挥作用,因此使用多酚类化合物来对抗衰老可能有助于衰老疗法的开发。在此背景下,我们评估了天然多酚类化合物白藜芦醇对间充质基质细胞 (MSC) 衰老的影响,MSC 在体内稳态中起着关键作用。我们的研究结果表明,白藜芦醇可减少因诱导急性衰老的遗传毒性应激和衰老复制培养而导致的衰老细胞数量。此外,这种衰老疗法活性促进了 MSC 细胞增殖和干性的恢复。总之,我们的研究结果表明,白藜芦醇通过靶向相关途径以及检测和影响 P53 依赖性和 P53 非依赖性衰老来对抗衰老,具有有效性。因此,我们的研究表明,鉴于白藜芦醇具有多种机制来实现其多效性活性,它可能能够对抗任何衰老表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/8a19b56d06c5/ijms-22-11619-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/7c714cbaa936/ijms-22-11619-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/021742daf760/ijms-22-11619-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/7d9ae7d44d2a/ijms-22-11619-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/8a19b56d06c5/ijms-22-11619-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/7c714cbaa936/ijms-22-11619-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/45e5e1c82f10/ijms-22-11619-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/021742daf760/ijms-22-11619-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/8583715/8a19b56d06c5/ijms-22-11619-g005.jpg

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