Rejuvenation Research

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia and is a significant contributor to the development and progression of diabetes. Oxidative stress has been linked to several symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, the present research aimed to evaluate the genetic abnormality of NQO1 (rs1800566, C609T) gene polymorphism, expression, and vitamin-D level assessment among Type 2 diabetes mellitus (T2DM) patients. The study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy controls. Total RNA was extracted from the whole blood using the TRIzol method, and further cDNA was synthesized, and expression was evaluated.

There is a significant difference in NQO1 (rs1800566, C609T) genotype distribution among the T2DM patients and healthy controls (p = 0.04). Compared with the NQO1 CC wild-type genotype, the NQO1 CT heterozygous genotype had an odds ratio of 1.96 (1.08–3.55), and the NQO1 TT mutant type genotype had an odds ratio of 3.31 (0.61–17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p < 0.0001) and homozygous mutant TT genotype (p = 0.0004), compared with homozygous wild-type CC genotype. NQO1 mRNA expression level was also compared with vitamin D levels among the T2DM patients. T2DM patients with vitamin D deficiency had 1.83-fold NQO1 mRNA expression, while vitamin D insufficient and sufficient T2DM cases had 3.31-fold (p < 0.0001) and 3.70-fold (p < 0.0001) NQO1 mRNA expression.

It was concluded that NQO1 (rs1800566, C609T) CT and TT genotypes played a significant role in the worseness of type II diabetes mellitus, and decreased expression of NQO1 mRNA expression could be an essential factor for disease worseness as well as hypermethylation could be a factor for reduced expression leading to disease severity. The decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype associated with vitamin D deficiency may contribute to disease progression.

Parkinson’s disease (PD) is a multifactorial degenerative disease in the elder. Given the involvement of mammalian sterile 20-like kinase 1 (MST1) in PD, this article was to illustrate the mechanism of MST1 in 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced PD cell model. Cells were treated with different concentrations of MPP⁺ to establish a PD cell model. Reverse transcription–quantitative polymerase chain reaction and Western blot revealed that MST1 expression and iron ion concentration increased, but cellular viability decreased with MPP⁺ concentration. Inhibition of MST1 decreased ferroptosis; increased cellular viability, iron ion content, and levels of glutathione peroxidase 4; and decreased reactive oxygen species and lactate dehydrogenase release. Upregulation of ferroptosis levels using ferroptosis agonist Erastin reduced the protective effect of MST1 inhibition on PD cells. Mechanistically, dual-luciferase analysis identified that miR-23b-3p targeted MST1 and inhibited its expression. Overexpression of miR-23b-3p inhibited MST1 levels, thereby reducing cellular ferroptosis and attenuating MPP⁺-induced cell injury. Collectively, MST1 expression increased with increasing MPP⁺ concentration, and miR-23b-3p targeted MST1 to reduce ferroptosis and MPP⁺-induced cell injury.

Chronic inflammation (inflammaging) is one of the important reasons for the development of age-related diseases and aging. Carrying out aging research and mining inflammatory markers can develop antiaging intervention targets, thus promoting healthy aging. By comparing the levels of inflammatory proteome in the serum of Chinese long-living people over 90 years and elderly aged 60∼79 which was detected by Olink platform, this study found that some pro-inflammatory or pro-aging proteins increased significantly in the long-living people, such as c-x-c motif chemokine ligand 9, accompanied by a significant increase in the levels of several anti-inflammatory or antiaging proteins, including fibroblast growth factor 19 and fibroblast growth factor 23, which confirmed that compared with elderly people, pro-inflammatory and anti-inflammatory (pro-aging and antiaging) tend to be balanced in long-living people, thus reducing the risk of age-related diseases and prolonging the lifespan of the elderly. These differently expressed proteins could serve as therapeutic targets and monitoring indicators for antiaging. At the same time, a few inflammatory protein markers, especially c-x-c motif chemokine ligand 9 and osteoprotegerin, could distinguish long-living and elderly correctly, which could be used to predict lifespan combined with other antiaging markers.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of postmitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a postmitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.