Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

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Abstract

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in the treatment of aging-related diseases. Sirtuin 1 (SIRT1), a member of NAD ⁺-dependent deacetylase enzyme family, is extensively explored as a potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against aging-related diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) and reperfusion (MI/R), Atherosclerosis (AS), and Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, SIRT1 regulates cellular senescence and multiple aging-related cellular processes, including SIRT1/Keap1/Nrf2/HO-1 and SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB and SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP and SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mediated mitochondrial damage, SIRT1/FoxO mediated autophagy, and SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin mediated neuroprotective effects. In this review, we summarized the role of SIRT1 in the improvement of the attenuation effect of quercetin on aging-related diseases and the relationship between relevant signaling pathways regulated by SIRT1. Moreover, the functional regulation of quercetin in aging-related markers such as oxidative stress, inflammatory response, mitochondrial function, autophagy and apoptosis through SIRT1 was discussed. Finally, the prospects of an extracellular vesicles (EVs) as quercetin loading and delivery, and SIRT1-mediated EVs as signal carriers for treating aging-related diseases, as well as discussed the ferroptosis alleviation effects of quercetin to protect against aging-related disease via activating SIRT1. Generally, SIRT1 may serve as a promising therapeutic target in the treatment of aging-related diseases via inhibiting oxidative stress, reducing inflammatory responses, and restoring mitochondrial dysfunction.

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The Hallmarks of Aging

Carlos López-Otín, Maria Blasco, Linda Partridge … (2014)

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

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A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.

Hadas Keren‐Shaul, Amit Spinrad, Assaf Weiner … (2017)

Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)(-/-) Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. VIDEO ABSTRACT.

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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Luigi Ferrucci, Elisa Fabbri (2018)

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.

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Author and article information

Contributors

Zhifu Cui: URI : https://loop.frontiersin.org/people/1127010

Xingtao Zhao: URI : https://loop.frontiersin.org/people/1850328

Felix Kwame Amevor: URI : https://loop.frontiersin.org/people/1024132

Xiaxia Du: URI : https://loop.frontiersin.org/people/1776114

Yan Wang: URI : https://loop.frontiersin.org/people/937190

Gang Shu: URI : https://loop.frontiersin.org/people/1127020

Yaofu Tian: URI : https://loop.frontiersin.org/people/1127018

Xiaoling Zhao: URI : https://loop.frontiersin.org/people/781439

Journal

Journal ID (nlm-ta): Front Immunol

Journal ID (iso-abbrev): Front Immunol

Journal ID (publisher-id): Front. Immunol.

Title: Frontiers in Immunology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-3224

Publication date (Electronic): 22 July 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 943321

Affiliations

[1] ¹ Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University , Chengdu, China

[2] ² State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine , Chengdu, China

[3] ³ Department of Basic Veterinary Medicine, Sichuan Agricultural University , Chengdu, China

Author notes

Edited by: Rama Vaidya, Medical Research Centre of the Kasturba Health Society (MRC-KHS), India

Reviewed by: Sun Young Park, Pusan National University, South Korea; Kangkang Guo, Northwest A&F University, China

*Correspondence: Xiaoling Zhao, zhaoxiaoling@ 123456sicau.edu.cn

†These authors have contributed equally to this work

This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Immunology

Article

DOI: 10.3389/fimmu.2022.943321

PMC ID: 9355713

PubMed ID: 35935939

SO-VID: fa145cfb-b91d-4df1-864d-c647d58982bb

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 13 May 2022

Date accepted : 27 June 2022

Page count

Figures: 10, Tables: 8, Equations: 0, References: 259, Pages: 26, Words: 10443

Funding

Funded by: Sichuan Province Science and Technology Support Program , doi 10.13039/100012542;

Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

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Most cited references 258

The Hallmarks of Aging

A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

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