Adaptive homeostasis and the free radical theory of ageing

Pomatto, Laura C.D.; Davies, Kelvin J.A.

doi:10.1016/j.freeradbiomed.2018.06.016

Cited by 157 publications

(105 citation statements)

References 234 publications

(281 reference statements)

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“…Growing evidence indicates that oxidation-reduction (redox)-based regulation of gene expression and adaptive homeostasis are fundamental regulatory mechanisms in cell biology. A great variety of protective systems against oxidative stress in poultry is suggested to be strictly regulated and, depending on the conditions, the stress response can be created over a period of minutes to hours, days to weeks, or months to years [102]. In this respect, signal transduction pathways such as the Nrf2-Keap1 system is one of the fastest responding systems to the changing environment which can upregulate the antioxidant defence network within minutes [102].…”

Section: The Concept Of Oxidative Stressmentioning

confidence: 99%

“…A great variety of protective systems against oxidative stress in poultry is suggested to be strictly regulated and, depending on the conditions, the stress response can be created over a period of minutes to hours, days to weeks, or months to years [102]. In this respect, signal transduction pathways such as the Nrf2-Keap1 system is one of the fastest responding systems to the changing environment which can upregulate the antioxidant defence network within minutes [102]. Mounting evidence has shown that detrimental alterations in redox signalling in stress conditions could lead to disease development [103] and losses in productive and reproductive poultry performances [15].…”

Section: The Concept Of Oxidative Stressmentioning

confidence: 99%

“…Adaptive homeostasis was presented as a mechanism explaining how variations in stress exposure (type, duration, intensity/strength, etc. ), including oxidative stress, are dealt with by a cooperative action of various protective mechanisms [102].…”

Section: The Concept Of Oxidative Stressmentioning

confidence: 99%

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Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

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Section: The Concept Of Oxidative Stressmentioning

confidence: 99%

Section: The Concept Of Oxidative Stressmentioning

confidence: 99%

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Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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“…S5). These mutations are known to be induced by oxidative damage (16), which itself has often been considered as a main driver of aging and age-related diseases (17).…”

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confidence: 99%

Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver

Brazhnik

Sun

Alani

et al. 2019

Preprint

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Accumulating somatic mutations have been implicated in age-related cellular degeneration and death. Because of their random nature and low abundance, somatic mutations are difficult to detect except in single cells or clonal lineages. Here we show that in single hepatocytes from human liver, an organ normally exposed to high levels of genotoxic stress, somatic mutation frequencies are high and increase substantially with age. Significantly lower mutation frequencies were observed in liver stem cells and organoids derived from them. These results could explain the increased age-related incidence of liver disease in humans and stress the importance of stem cells in maintaining genome integrity.Genome integrity is critically important for cellular function. Evidence has accumulated that loss of genome integrity and the increasingly frequent appearance of various forms of genome instability, from chromosomal aneuploidy to base substitution mutations, is a hallmark of aging (1, 2). However, somatic mutations occur de novo across cells and tissues and are of low abundance. Hence, thus far, of all mutation types only chromosomal alterations could readily be studied directly during in vivo aging using cytogenetic methods (3). More recently it has become possible to also study low-abundant somatic mutations by whole genome sequencing (WGS) of single cells or clones derived from single cells (4-7). Such studies confirmed that like chromosomal alterations also base substitution mutations accumulate with age in human brain (8,9), intestine and liver (4).Due to its high metabolic and detoxification activity liver is more likely to be adversely affected by various damaging agents than most other organs. In humans this may cause agerelated loss of function, most notably a severe reduction in metabolic capacity and multiple pathologies, including fatty liver disease, cirrhosis, hepatitis, infections and cancer (10,11). To test if somatic mutations occur with a high frequency and accumulate rapidly with age we performed WGS on single primary hepatocytes from human donors varying in age between 5 months and 77 years of age. These cells were isolated from healthy human individuals shortly after death through perfusion of whole donor livers (Lonza Walkersville Inc.). Cell viability was higher than 80% and, after staining with Hoechst, hepatocytes were isolated via FACS into individual PCR tubes as diploid single cells (Fig. S1). In total we sequenced 4 single hepatocytes and bulk genomic liver DNA for each of eight human donors (Table S1). Each cell was subjected to our recently developed procedure for whole genome amplification (WGA) and sequencing (5,6). Somatic single nucleotide variants (SNVs) in single cells were identified relative to bulk genomic DNAs at a depth of ≥ 20X using a combination of VarScan2, MuTect2 and Haplotypecaller software with certain modifications (Methods , Table S2). Overlapping mutations, revealed by all three analytical tools, were exclusively considered for further analysis.After adjusting for genomic ...

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“…A variety of hypotheses have been suggested to explain the mechanism of aging, including the theory free radicals of aging proposed by Pr Harman in 1956 [10,11], which was certainly the most widely studied. This theory continues to be revised, and so far, it remains a sound theory for the aging process [9,10]. The theory explains that aging may be caused by the cumulative oxidative stress, leading to oxidative damage to various macromolecules (membrane lipids, proteins, DNA) within the cell, which may lead to cell death and possibly to the death of the organism [10].…”

Section: Introductionmentioning

confidence: 99%

Almond Skin Extracts and Chlorogenic Acid Delay Replicative Aging by Enhanced Oxidative Stress Response Involving SIR2 and SOD2 in Yeast

Abid¹,

Elamrani²,

Drouet³

et al. 2020

Preprint

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Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

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Adaptive homeostasis and the free radical theory of ageing

Cited by 157 publications

References 234 publications

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver

Almond Skin Extracts and Chlorogenic Acid Delay Replicative Aging by Enhanced Oxidative Stress Response Involving SIR2 and SOD2 in Yeast

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