DNA methylation in genes associated with the evolution of ageing and disease: A critical review

Auley, Mark T. Mc

doi:10.1016/j.arr.2021.101488

Cited by 20 publications

(6 citation statements)

References 249 publications

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“…To date, various causes of age-related changes in methylation of tumor suppressor genes have been identified. In particular, an increase in the degree of circulating DNA methylation is associated with a change in the activity of the methylation system as well as with the influence of carcinogens and environmental factors [ 42 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Тамкович

Tupikin

Kozyakov³

et al. 2022

IJMS

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Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA.

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Section: Discussionmentioning

confidence: 99%

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Тамкович

Tupikin

Kozyakov³

et al. 2022

IJMS

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“…Studies conducted recently have revealed disparities between males and females in intricate human ailments and have presented proof that DNA methylation, which can be affected by gender, governs biological mechanisms that could potentially impact human diseases [ 38 ]. Studies have recorded disparities in DNA methylation based on gender in genes associated with cardiovascular disorders, lipid processing, lipid concentrations, and the aging process [ 39 ]. Our study analyzed the average methylation levels of the VGLL3 gene in both the control group and the general population.…”

Section: Discussionmentioning

confidence: 99%

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations

Liu,

Chen,

Zhang

et al. 2024

Bioscience Reports

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DNA methylation is widely recognized to play a role in intracranial aneurysm (IA) pathogenesis. We investigated the levels of methylation of vestigial-like 3 (VGLL3) in IA, and explored its potential as a prognostic indicator. A total of 48 patients with IA and 48 healthy controls were included in this study. Methylation levels of CpG sites were assessed using bisulfite pyrosequencing, and levels of VGLL3, TEAD, and YAP in the blood were measured by real-time quantitative polymerase chain reaction testing. VGLL3 methylation was significantly higher in controls than in IA patients (p = 0.001), and this phenomenon was more pronounced in females (p < 0.001). Compared with the control group, the expression levels of VGLL3 and TEAD in the blood of IA patients were significantly increased, while YAP was significantly decreased. VGLL3 methylation was positively correlated with HDL (p = 0.003) and female Lpa concentration (r = 0.426, p = 0.03), and was also negatively correlated with age (p = 0.003), APOE (p = 0.005) and VGLL3 mRNA expression (p <0.001). Methylation and mRNA expression of VGLL3 may serve as indicators of IA risk in females (AUC = 0.810 and 0.809). VGLL3 methylation may participate in the pathogenesis of IA by regulating the expression of the VGLL3/TEAD/YAP pathway, and its gene methylation and expression levels have IA risk prediction value.

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“…There are several theories of ageing [ 1 , 21 , 22 ], but one of the most popular and most widely supported approaches has been proposed by López-Otín et al [ 23 ], who defined ageing in different categories and explained the interactions between various factors stimulating the development of age-related changes and diseases. For example, Gonçalves et al [ 24 ] described the major causes of ageing related to epigenetic changes associated with gene expression [ 25 ], e.g., global DNA methylation in genes [ 26 ], epigenetic alterations, genomic instability, and mitochondrial dysfunction related to the mitochondrial DNA copy number, depletion of telomeres on chromosomes or telomere attrition, and changes in proteostasis processes leading to the accumulation of cellular waste by Hsp70 and Hsp72 markers [ 27 ]. The relative contribution of energetic and functional barriers to the evolution and manifestation of ageing is discussed in the work of the authors [ 28 ].…”

Section: Biological Mechanisms Of the Ageing Processmentioning

confidence: 99%

Tricarboxylic Acid Cycle Intermediates and Individual Ageing

Kurhaluk

2024

Biomolecules

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Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans, Drosophila, mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.

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DNA methylation in genes associated with the evolution of ageing and disease: A critical review

Cited by 20 publications

References 249 publications

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations

Tricarboxylic Acid Cycle Intermediates and Individual Ageing

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