Table 3.
Compounds preventing DNA damage due to epigenetic regulation, telomere maintenance, and nuclear architecture modulation.
| Compounds | Mechanisms | References |
|---|---|---|
| Trace elements | ||
| Selenium | Global DNA methylation increase, LINE-1 methylation. Regulation of the expression of DNMT1, DNMT3a, DNMT3b. Influence on active and repressive histone marks. HDAC1 inhibition. |
[144,751,752,753] |
| Zinc | Changes in the methylation status of hTERT promoter. Inhibition of global DNA hypomethylation and H3K9 acetylation. Increase in the metallothionein IV mRNA expression due to the reduced DNA methylation and increased H3K9ac of the promoter. |
[679,754,755,756] |
| Iron | Modulation of DNA demethylation due to TET enzymes. Participation in the facultative heterochromatin assembly. |
[757,758] |
| Magnesium | Mediates the nucleosome self-assembly and DNA self-assembly, heterochromatin formation. | [759,760,761] |
| Manganese | Influence on epigenetic modifications (particularly, reducing DNA methylation and increasing H3K9 acetylation). Inhibition of the acetylation of core histones and regulation of the activity of HDACs and HATs. |
[162,762] |
| Vitamins and their derivatives | ||
| Vitamin A | Influence on global and site-specific DNA methylation profiles. | [763,764] |
| Retinoic acid | Regulation of epigenetic processes, including DNA methylation, histone modifications, the formation of polycomb repressive complex 2, and induction of transcription factors. The decrease in DNMT1 and DNMT3b expression. Repressive chromatin-remodeling mediated by RIP140, G9a, and HP1γ. The decrease in the progerin and prelamin A expression. |
[765,766,767,768,769,770,771,772,773,774] |
| Vitamin B3 | NAD+ precursor, it provides sirtuin activity. HDAC III inhibitor, determines heterochromatin remodeling. |
[775,776,777,778] |
| Nicotinamide mononucleotide (a niacin derivative) | Activation of sirtuins. Anti-aging changes in the miRNA expression profile. |
[684,779] |
| Vitamin B9 | Regulation of DNA methylation and heterochromatin structure. DNMT activation. |
[175,674,780,781] |
| Vitamin B12 | Regulation of DNA methylation. | [780] |
| Vitamin C | Regulation of DNA methylation due to TET activity (vitamin C is a TET co-factor). Alteration of the expression of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways. Prevention of the heterochromatin disorganization. Inhibition of the expression of prelamin A and prevention of the nuclear lamina disorganization. |
[180,782,783,784,785] |
| Vitamin D3 | Association with DNA methylation age. Increase in global DNA methylation. Enhancement of the LINE-1 methylation and suppression of the endogenous retroviruses activity. Gene-specific hypomethylation and inhibition of DNMT1 и DNMT3B. NAD+ level decreases and SIRT1 activation. Reduction of progerin production. |
[190,690,786,787,788,789,790] |
| Vitamin E | Increase in global DNA methylation. Induction of the MLH1 and DNMT1 gene expression. |
[763,791,792] |
| Amino Acids | ||
| Trimethylglycine (Betaine) | Modulation of global DNA methylation. | [793,794,795] |
| Methionine | Modulation of DNA methylation. Determination of the activity of TETs and DNMT1. |
[796,797] |
| Choline | Modulation of DNA methylation. Determination of the activity of TETs and DNMT1. |
[795,796] |
| N-Acetylcysteine | Reduce of DNA hypermethylation. Increase in the expression sirtuins. Prevention of chromatin decondensation. Decrease in prelamin A. |
[237,698,798,799] |
| Polyphenols | ||
| Epigallocatechin gallate | It can influence methylation patterns and the activity of DNMT1. Inhibition of DNMT1 and demethylation of the DNA repair gene promoter. HDAC inhibition and SIRT1 activation. Promotion of chromatin relaxation. Increase in histone acetylation (H3K9/14ac, H3ac), and methylation of both active (H3K4me3) and repressive (H3K9me3) chromatin marks. Influence on the expression of epigenome modulators. |
[578,800,801,802,803,804] |
| Luteolin | HAT inhibition and SIRT1 activation. | [805] |
| Chrysin | Binding with the active site of SAM-dependent methyltransferase. | [806] |
| Curcumin | Locus-specific modulation of DNA methylation. Restoration of the DNA methylation status, expression of DNMTs, MBD4, MeCP2 after genotoxic treatment. Gene-specific hypomethylation (in the case of BRCA1 promoter) by upregulation of the TET1 gene. Increase in the LINE-1 methylation. Influence on the SIRT1 and p300/CBP signaling pathways. It can act as an HDAC inhibitor. Modulates chromatin condensation. |
[807,808,809,810,811,812,813,814] |
| Quercetin | Influence on the chromatin condensation and restoration of the heterochromatin architecture. Modulation of different proteins related to epigenetic modifications. SIRT1 activation and HDAC inhibitor. |
[815,816,817] |
| Rutin | Modulation of miRNA and lncRNA profiles. Particularly, the regulation of the miRNA expression associated with DNA repair. | [818,819,820] |
| Hyperoside | SIRT1 activation. | [318] |
| Kaempferol | SIRT1 deacetylase activity stimulation. | [322] |
| Morin | Prevention of the chromatin condensation and hypodiploid DNA in stress conditions. Restoration of the miRNA profile. |
[327,330] |
| Fisetin | HAT inhibition and SIRT1 activation. | [805] |
| Naringin | Prevention of chromatin hypercondensation. | [821,822] |
| Silymarin and flavonolignans (Silybin) |
Stimulation of SIRT1. | [823] |
| Genistein | Decrease in the gene-specific DNA methylation (including tumor suppressor genes). Modulation of DNA methylation, histone modification patterns, and the activity of chromatin-remodeling proteins. Modification of the binding topology of chromatin-bound proteins. |
[824,825,826,827] |
| Daidzein | Modulation of DNA methylation, histone modification patterns, and the activity of chromatin-remodeling proteins. | [826,827] |
| Grape seed procyanidin and proanthocyanidins | Mediation of the DNMT and HDAC activity. The decrease in the expression of miRNA-153 preventing the post-transcriptional repression of Nrf2 (as well as AKT and GSK-3β). |
[382,828,829] |
| Cyanidin | SIRT6 activation. | [830] |
| Cyanidin-3-O-glucoside | Prevention of histone modifications. | [831] |
| Pelargonidin | Mediation of the DNMT and HDAC activity. The decrease in the DNA methylation in the NRF2 promoter. |
[395] |
| Resveratrol | Activator of SIRT1 and other sirtuins. Increases SIRT1 binding with lamin A. The decrease in the acetylation of histones and other target proteins (particularly, p53). Modulation chromatin condensation. Reversion of the activity of DNMTs and the methylation of LINE-1. Modulation of the activity of miR-135a and other miRNAs that influences the sirtuin activity and the expression of DNA repair proteins (particularly, KU70 и WRN). It causes chromatin compaction but can decrease DNA repair rates. |
[717,718,832,833,834,835,836,837,838,839,840] |
| Ellagic acid | SIRT1 activator. | [841] |
| Gallic acid | Activation of TLK1 that mediates chromatin remodeling, replication, DNA damage response, and repair. | [842,843] |
| Terpenes and terpenoids | ||
| Ursolic acid | Changes of the DNA methylation pattern and histone methylation (due to the SETD7 methyltransferase), particularly targeted on the NRF2 signaling. | [501,844] |
| Ginsenosides | Regulation of the NAD-PARP-SIRT signaling pathway. Up-regulation of the miR-15b expression and prevention of DNA damage by an influenza virus. |
[845,846] |
| Organic acids | ||
| α-Lipoic acid | Stimulation of SIRT1, SIRT3, and their targets (FOXO3a, PGC1β). | [553,847] |
| β-Hydroxybutyrate | Prevention of heterochromatin instability. Activation of SIRT1. |
[848,849] |
| Isothiocyanates | ||
| Sulforaphane | Regulation of cell cycle and DNA damage response by influencing transcription patterns and DNA methylation. HDAC inhibition, enhancement of the histone H4 acetylation status. Enhancement of the progerin clearance by autophagy. |
[850,851,852,853,854] |
| Polyamines | ||
| Spermidine | Regulation of DNA conformation and chromatin condensation. Impairment of the interaction between lamin A and CK2 promoting DNA damage repair. |
[855,856] |
| Spermine | Regulation of DNA conformation and chromatin condensation. | [856,857] |
| Hormones | ||
| Melatonin | Modulation of DNA methylation patterns and histone marks. Participation in the chromatin packaging. Demethylation of promoters of antioxidant defense genes (SOD1, GPx, CAT). SIRT1 activation. Inhibition of miR-24, which targets genes involved in the DNA damage response and repair, and other processes. Prevention of the inhibition of the lncRNA H19 and miR-675 that regulate DNA damage response and cellular senescence. |
[730,858,859,860,861,862] |
| 17β-Estradiol | Telomere length increases. Modulation of DNA methylation patterns, histone marks, and the activity of chromatin-remodeling proteins. |
[827,863] |
| Synthetic compounds | ||
| SRT2183 | Activation of SIRT1 and stimulation of DNA damage response. | [864] |
| Exifone | HDAC1 activator that modulates OGG1 expression. | [61] |
| Trichostatin A | HDAC inhibitor that decreases chromatin condensation. Promotion of prompt and slow DNA repair in the open chromatin conformation. Inhibition of deacetylation of H3K18 acetylation in the promoter regions of NER genes. |
[865,866,867,868] |
| Suberoylanilide hydroxamic acid (SAHA, Vorinostat) | HDAC inhibitor that decreases chromatin condensation. Restoration of acetylation levels of H3 and H4 after irradiation. Prevention of elevated recruitment of DNMT1 and DNMT3b to the promoter of a DNA repair gene (OGG1). Abrogation of viral DNA amplification and inhibition of DNA replication in infected cells (but not in uninfected). |
[869,870,871,872] |
| Valproic acid | HDAC inhibitor that decreases chromatin condensation. Modulation of the antioxidant defense. Initiation of DNA damage response due to histone acetylation regulation. Relaxing chromatin state stimulates immediate DNA repair. Enhancement of the DNA sensitivity to specific enzymes and increase in the interaction with intercalating agents. |
[625,626,869,873,874] |
| RG108 | DNMT inhibitor. Blocking methylation at the TERT promoter and increasing its expression. Modulation of the antioxidant defense. Decrease in marks of DNA damage and cellular senescence. |
[626,734,875] |
| Farnesyltransferase inhibitor | Chromosome positioning in the nuclei. | [735] |
| Metformin | Restoration of the NAD+ level (by AMPK activation). Increase in the SIRT1 gene and protein expression, and SIRT1 promoter chromatin accessibility. The decrease in the progerin expression and alteration of the LMNA pre-mRNA splicing ratio. Normalization of the expression of microRNAs after genotoxic treatment. |
[609,736,876,877,878,879,880] |
| Rapamycin | Slowing of epigenetic aging. Modulation of DNA methylation. Restoration of the SIRT1 localization and distribution of chromatin markers. Elicits release of the transcription factor Oct-1. Induction of the autophagic degradation of progerin and prelamin A. Recovery of chromatin-associated nuclear envelope proteins LAP2α and BAF. |
[738,772,881,882] |