An NRF2 Perspective on Stem Cells and Ageing

Dodson, Matthew; Anandhan, Annadurai; Zhang, Donna D.; Madhavan, Lalitha

doi:10.3389/fragi.2021.690686

Cited by 18 publications

(16 citation statements)

References 155 publications

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“…These stress-sensitive transcription factors function both in acute challenge and as regulators of early antioxidant activity. In the oxidative stress theory of ageing, it is postulated that oxidative damage to biological macromolecules is a key factor in ageing [ 111 , 112 , 113 ]. Thus, mechanisms that slow down the accumulation of oxidation products in the cells and tissues of an organism may promote longevity.…”

Section: Effects Of Polyphenols On Proteostasis Lossmentioning

confidence: 99%

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

Pereira

Santos

Fortunato

et al. 2023

IJMS

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Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects.

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Section: Effects Of Polyphenols On Proteostasis Lossmentioning

confidence: 99%

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

Pereira

Santos

Fortunato

et al. 2023

IJMS

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“…Nrf2 is recognized as a key regulator of antioxidants in the CNS and serves as a neuroprotection in response to oxidative stress [ 112 , 113 ]. Nrf2 declines with age and is further exposed to oxidative stress during acute inflammation [ 114 ]. This phenomenon could explain the vulnerable brain theory in the occurrence of delirium in the elderly.…”

Section: Role Of the Tryptophan-kynurenine Pathway In Deliriummentioning

confidence: 99%

Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature

Phing

Makpol

Nasaruddin

et al. 2023

IJMS

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Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.

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“…In normal ageing, NRF2 activity, as well as expression of NRF2 target genes, decrease with age in many organs, including the brain [ 181 , 182 ] ( Table 3 ). Consequently, the antioxidant/oxidant equilibrium is disrupted during brain ageing, thus favouring oxidative stress and associated damage.…”

Section: Nrf2 and Brain (Dys)functionsmentioning

confidence: 99%

“…Multiple studies show that NRF2, whose activity is reduced during ageing, can be considered as a targetable pathway [ 181 , 182 , 192 , 193 ]. Thus, the activation of NRF2 in ageing could theoretically be beneficial.…”

Section: Nrf2 and Brain (Dys)functionsmentioning

confidence: 99%

Normal and Pathological NRF2 Signalling in the Central Nervous System

et al. 2022

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The nuclear factor erythroid 2-related factor 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, cellular detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed to this pleiotropic transcription factor that regulates hundreds of genes. After 40 years of in-depth research and key discoveries, NRF2 is now at the center of a vast regulatory network, revealing NRF2 signalling as increasingly complex. It is widely recognized that reactive oxygen species (ROS) play a key role in human physiological and pathological processes such as ageing, obesity, diabetes, cancer, and neurodegenerative diseases. The high oxygen consumption associated with high levels of free iron and oxidizable unsaturated lipids make the brain particularly vulnerable to oxidative stress. A good stability of NRF2 activity is thus crucial to maintain the redox balance and therefore brain homeostasis. In this review, we have gathered recent data about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, cancer, ageing, and ageing-related neurodegenerative diseases. We also discuss promising therapeutic strategies and the need for better understanding of cell-type-specific functions of NRF2 in these different fields.

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An NRF2 Perspective on Stem Cells and Ageing

Cited by 18 publications

References 155 publications

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature

Normal and Pathological NRF2 Signalling in the Central Nervous System

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