Cellular senescence due to genomic instability is believed to be one of the mechanisms causing health problems in diabetes mellitus (DM). Low methylation levels of Alu elements or Alu hypomethylation, an epigenomic event causing genomic instability, were commonly found in aging people and patients with aging phenotypes, such as osteoporosis. We investigate Alu methylation levels of white blood cells of type 2 DM, pre-DM, and control. The DM group possess the lowest Alu methylation (P < 0.001, P < 0.0001 adjusted age). In the DM group, Alu hypomethylation is directly correlated with high fasting blood sugar, HbA1C, and blood pressure. Genome-wide hypomethylation may be one of the underlining mechanisms causing genomic instability in type 2 DM. Moreover, Alu methylation levels may be a useful biomarker for monitoring cellular senescence in type 2 DM patients.

Caenorhabditis elegans (C. elegans) has emerged as an outstanding model organism for investigating the aging process due to its shortened lifespan, well-defined genome, and accessibility of potent genetic tools. This review presents the current findings on chronological aging and photoaging in C. elegans, exploring the elaborate molecular pathways that control these processes. The progression of chronological aging is characterized by a gradual deterioration of physiological functions and is influenced by an interaction of genetic and environmental factors, including the insulin/insulin-like signaling (IIS) pathway. In contrast, photoaging is characterized by increased oxidative stress, DNA damage, and activation of stress response pathways induced by UV exposure. Although the genetic mechanisms of chronological aging in C. elegans have been characterized by extensive research, the pathways regulating photoaging are comparatively less well-studied. Here, we provide an overview of the current understanding of aging research, including the crucial genes and genetic pathways involved in the aging and photoaging processes of C. elegans. Understanding the complex interactions between these factors will provide invaluable insights into the molecular mechanisms underlying chronological aging and photoaging and may lead to novel therapeutic approaches and further studies for promoting healthy aging in humans.

Introduction: Epigenetic changes that cause genomic instability may be the basis of pathogenic processes of age-associated noncommunicable diseases (NCDs). Essential hypertension is one of the most common NCDs. Alu hypomethylation is an epigenetic event that is commonly found in elderly individuals. Epigenomic alterations are also found in age-associated NCDs such as osteoporosis and diabetes mellitus. Alu methylation prevents DNA from being damaged. Therefore, Alu hypomethylated DNA accumulates DNA damage and, as a result, causes organ function deterioration. Here, we report that Alu hypomethylation is a biomarker for essential hypertension. Results: We investigated Alu methylation levels in white blood cells from normal controls, patients with prehypertension, and patients with hypertension. The hypertension group possessed the lowest Alu methylation level when classified by systolic blood pressure and diastolic blood pressure (P = 0.0002 and P = 0.0088, respectively). In the hypertension group, a higher diastolic blood pressure and a lower Alu methylation level were observed (r = -0.6278). Moreover, we found that changes in Alu hypomethylation in the four years of follow-up in the same person were directly correlated with increased diastolic blood pressure. Conclusions: Similar to other age-associated NCDs, Alu hypomethylation is found in essential hypertension and is directly correlated with severity, particularly with diastolic blood pressure. Therefore, Alu hypomethylation may be linked with the molecular pathogenesis of high blood pressure and can be used for monitoring the clinical outcome of this disease.

Replication-independent endogenous double-strand breaks (RIND-EDSBs) occur in both humans and yeast in the absence of inductive agents and DNA replication. In human cells, RIND-EDSBs are hypermethylated, preferentially retained in the heterochromatin and unbound by γ-H2AX. In single gene deletion yeast strains, the RIND-EDSB levels are altered; the number of RIND-EDSBs is higher in strains with deletions of histone deacetylase, endonucleases, topoisomerase, or DNA repair regulators, but lower in strains with deletions of the high-mobility group box proteins or Sir2. In summary, RIND-EDSBs are different from pathologic DSBs in terms of their causes and consequences. In this study, we identified the nucleotide sequences surrounding RIND-EDSBs and investigated the features of these sequences as well as their break locations. In recent work, we detected RIND-EDSBs using ligation mediated PCR. In this study, we sequenced RIND-EDSB PCR products of resting state Saccharomyces cerevisiae using next-generation sequencing to analyze RIND-EDSB sequences. We found that the break locations are scattered across a number of chromosomes. The number of breaks correlated with the size of the chromosomes. Most importantly, the break occurrences had sequence pattern specificity. Specifically, the majority of the breaks occurred immediately after the sequence “ACGT” (P = 2.2E-156). Because the “ACGT” sequence does not occur primarily in the yeast genome, this specificity of the “ACGT” sequence cannot be attributed to chance. RIND-EDSBs occur non-randomly; that is, they are produced and retained by specific mechanisms. Because these particular mechanisms regulate their generation and they possess potentially specific functions, RIND-EDSBs could be epigenetic marks.

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.

Introduction: Alu 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.Results: We 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).Conclusions: Alu 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.