The roles of <scp>HMGB1</scp>‐produced <scp>DNA</scp> gaps in <scp>DNA</scp> protection and aging biomarker reversal

Yasom, Sakawdaurn; Watcharanurak, Papitchaya; Bhummaphan, Narumol; Thongsroy, Jirapan; Puttipanyalears, Charoenchai; Settayanon, Sirapat; Chalertpet, Kanwalat; Khumsri, Wilunplus; Kongkaew, Aphisek; Patchsung, Maturada; Siriwattanakankul, Chutha; Pongpanich, Monnat; Pin‐on, Piyapat; Jindatip, Depicha; Wanotayan, Rujira; Odton, Mingkwan; Supasai, Suangsuda; Oo, Thura Tun; Arunsak, Busarin; Pratchayasakul, Wasana; Chattipakorn, Nipon; Mutirangura, Apiwat

doi:10.1096/fba.2021-00131

Cited by 20 publications

(32 citation statements)

References 73 publications

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“…The formation of DNA gaps is one of the cellular mechanisms that maintains DNA integrity. As a result, the role of youth-DNA-gaps is similar to that of gaps that remain between successive rails in a railway track, that is, relieving torsion force to prevent damage 33 . We previously demonstrated that reducing the DNA gap resulted in DNA shearing 37 .…”

Section: Introductionmentioning

confidence: 99%

“…We previously demonstrated that reducing the DNA gap resulted in DNA shearing 37 . Moreover, introducing new Box A-produced DNA gaps increased DNA resistance to radiation-induced DNA breaks, rejuvenated senescent cells, and rejuvenated both naturally and d-galactose-induced aging rats 33 . Two types of DNA breaks occur in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

“…In aging cells, pathologic breaks are actively produced; however, the overall number of DNA gaps that could be detected by DNA gap PCR is reduced 37 . Therefore, DNA gap PCR results can indicate the youthfulness of eukaryotic DNA 33 , 37 . Type 2 DM accelerates the aging process both at the molecular level and in terms of physical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

Thongsroy,

Mutirangura

2023

Sci Rep

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Naturally occurring DNA gaps have been observed in eukaryotic DNA, including DNA in nondividing cells. These DNA gaps are found less frequently in chronologically aging yeast, chemically induced senescence cells, naturally aged rats, d-galactose-induced aging model rats, and older people. These gaps function to protect DNA from damage, so we named them youth-associated genomic stabilization DNA gaps (youth-DNA-gaps). Type 2 diabetes mellitus (type 2 DM) is characterized by an early aging phenotype. Here, we explored the correlation between youth-DNA-gaps and the severity of type 2 DM. Here, we investigated youth-DNA-gaps in white blood cells from normal controls, pre-DM, and type 2 DM patients. We found significantly decreased youth-DNA-gap numbers in the type 2 DM patients compared to normal controls (P = 0.0377, P = 0.0018 adjusted age). In the type 2 DM group, youth-DNA-gaps correlate directly with HbA1c levels. (r = − 0.3027, P = 0.0023). Decreased youth-DNA-gap numbers were observed in patients with type 2 DM and associated with increased HbA1c levels. Therefore, the decrease in youth-DNA-gaps is associated with the molecular pathogenesis of high blood glucose levels. Furthermore, youth-DNA-gap number is another marker that could be used to determine the severity of type 2 DM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

Thongsroy,

Mutirangura

2023

Sci Rep

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“…Alu methylation, a specific form of DNA methylation, has been shown to play a role in minimizing the accumulation of endogenous DNA damage 30 . This effect is achieved by reducing the torsional force on the DNA double helix through naturally occurring hypermethylated DNA gaps 31–35 . Previous studies have indicated that type 2 DM patients accumulated DNA damage, 36–38 leading to genomic instability and cellular senescence 39,40 .…”

Section: Introductionmentioning

confidence: 99%

“…30 This effect is achieved by reducing the torsional force on the DNA double helix through naturally occurring hypermethylated DNA gaps. [31][32][33][34][35] Previous studies have indicated that type 2 DM patients…”

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confidence: 99%

Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels

Thongsroy,

Mutirangura

2023

Clinical Laboratory Analysis

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IntroductionAlu hypomethylation is a common epigenetic process that promotes genomic instability with aging phenotypes, which leads to type 2 diabetes mellitus (type 2 DM). Previously, our results showed significantly decreased Alu methylation levels in type 2 DM patients. In this study, we aimed to investigate the longitudinal changes in Alu methylation levels in these patients.ResultsWe observed significantly decreased Alu methylation levels in type 2 DM patients compared with normal (p = 0.0462). Moreover, our findings demonstrated changes in Alu hypomethylation over a follow‐up period within the same individuals (p < 0.0001). A reduction in Alu methylation was found in patients with increasing HbA1c levels (p = 0.0013) and directly correlated with increased HbA1c levels in type 2 DM patients (r = −0.2273, p = 0.0387).ConclusionsAlu methylation in type 2 DM patients progressively decreases with increasing HbA1c levels. This observation suggests a potential association between Alu hypomethylation and the underlying molecular mechanisms of elevated blood glucose. Furthermore, monitoring Alu methylation levels may serve as a valuable biomarker for assessing the clinical outcomes of type 2 DM.

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DNA damage, epigenetics, and aging

Mutirangura¹

2022

Epigenetics and DNA Damage

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The roles of HMGB1‐produced DNA gaps in DNA protection and aging biomarker reversal

Cited by 20 publications

References 73 publications

The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels

DNA damage, epigenetics, and aging

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