The biggest drawback of a current diabetes therapy is the treatment of the consequences not the cause of the disease. Regardless of the diabetes type, preservation and recovery of functional pancreatic beta cells stands as the biggest challenge in the treatment of diabetes. Free radicals and oxidative stress are among the major mediators of autoimmune destruction of beta cells in type 1 diabetes (T1D) or beta cell malfunction and death provoked by glucotoxicity and insulin resistance in type 2 diabetes (T2D). Additionally, oxidative stress reduces functionality of beta cells in T2D by stimulating their de-/trans-differentiation through the loss of transcription factors critical for beta cell development, maturity and regeneration. This review summarizes up to date clarified redox-related mechanisms involved in regulating beta cell identity and death, underlining similarities and differences between T1D and T2D. The protective effects of natural antioxidants on the oxidative stress-induced beta cell failure were also discussed. Considering that oxidative stress affects epigenetic regulatory mechanisms involved in the regulation of pancreatic beta cell survival and insulin secretion, this review highlighted huge potential of epigenetic therapy. Special attention was paid on application of the state-of-the-art CRISPR/Cas9 technology, based on targeted epigenome editing with the purpose of changing the differentiation state of different cell types, making them insulin-producing with ability to attenuate diabetes. Clarification of the above-mentioned mechanisms could provide better insight into diabetes etiology and pathogenesis, which would allow development of novel, potentially more efficient therapeutic strategies for the prevention or reversion of beta cell loss.

The progressively older population in developed countries is reflected in an increase in the number of people suffering from age-related chronic inflammatory diseases such as metabolic syndrome, diabetes, heart and lung diseases, cancer, osteoporosis, arthritis, and dementia. The heterogeneity in biological aging, chronological age, and aging-associated disorders in humans have been ascribed to different genetic and environmental factors (i.e., diet, pollution, stress) that are closely linked to socioeconomic factors. The common denominator of these factors is the inflammatory response. Chronic low-grade systemic inflammation during physiological aging and immunosenescence are intertwined in the pathogenesis of premature aging also defined as ‘inflammaging.’ The latter has been associated with frailty, morbidity, and mortality in elderly subjects. However, it is unknown to what extent inflammaging or longevity is controlled by epigenetic events in early life. Today, human diet is believed to have a major influence on both the development and prevention of age-related diseases. Most plant-derived dietary phytochemicals and macro- and micronutrients modulate oxidative stress and inflammatory signaling and regulate metabolic pathways and bioenergetics that can be translated into stable epigenetic patterns of gene expression. Therefore, diet interventions designed for healthy aging have become a hot topic in nutritional epigenomic research. Increasing evidence has revealed that complex interactions between food components and histone modifications, DNA methylation, non-coding RNA expression, and chromatin remodeling factors influence the inflammaging phenotype and as such may protect or predispose an individual to many age-related diseases. Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents. Here, we will summarize the epigenetic actions of dietary components, including phytochemicals, and macro- and micronutrients as well as metabolites, that can attenuate inflammaging. We will discuss the challenges facing personalized nutrition to translate highly variable interindividual epigenetic diet responses to potential individual health benefits/risks related to aging disease.

In the past decade, precise targeting through genome editing has emerged as a promising alternative to traditional therapeutic approaches. Genome editing can be performed using various platforms, where programmable DNA nucleases create permanent genetic changes at specific genomic locations due to their ability to recognize precise DNA sequences. Clinical application of this technology requires the delivery of the editing reagents to transplantable cells ex vivo or to tissues and organs for in vivo approaches, often representing a barrier to achieving the desired editing efficiency and safety. In this review, authored by members of the GenE-HumDi European Cooperation in Science and Technology (COST) Action, we described the plethora of delivery systems available for genome-editing components, including viral and non-viral systems, highlighting their advantages, limitations, and potential application in a clinical setting.

Diabetes is a complex metabolic disorder resulting either from insulin resistance or an impaired insulin secretion. Prolonged elevated blood glucose concentration, the key clinical sign of diabetes, initiates an enhancement of reactive oxygen species derived from glucose autoxidation and glycosylation of proteins. Consequently, chronic oxidative stress overwhelms cellular endogenous antioxidant defenses and leads to the acute and long-standing structural and functional changes of macromolecules resulting in impaired cellular functioning, cell death and organ dysfunction. The oxidative stress provoked chain of pathological events over time cause diabetic complications such as nephropathy, peripheral neuropathy, cardiomyopathy, retinopathy, hypertension, and liver disease. Under diabetic conditions, accompanying genome/epigenome and metabolite markers alterations may also affect glucose homeostasis, pancreatic β-cells, muscle, liver, and adipose tissue. By providing deeper genetic/epigenetic insight of direct or indirect dietary effects, nutrigenomics offers a promising opportunity to improve the quality of life of diabetic patients. Natural plant extracts, or their naturally occurring compounds, were shown to be very proficient in the prevention and treatment of different pathologies associated with oxidative stress including diabetes and its complications. Considering that food intake is one of the crucial components in diabetes’ prevalence, progression and complications, this review summarizes the effect of the major plant secondary metabolite and phytoconstituents on the antioxidant enzymes activity and gene expression under diabetic conditions.

Diabetes mellitus is a life-threatening multifactorial metabolic disorder characterized by high level of glucose in the blood. Diabetes and its chronic complications have a significant impact on human life, health systems, and countries’ economies. Currently, there are many commercial hypoglycemic drugs that are effective in controlling hyperglycemia but with several serious side-effects and without a sufficient capacity to significantly alter the course of diabetic complications. Over many centuries mushrooms and their bioactive compounds have been used in the treatment of diabetes mellitus, especially polysaccharides and terpenoids derived from various mushroom species. This review summarizes the effects of these main mushroom secondary metabolites on diabetes and underlying molecular mechanisms responsible for lowering blood glucose. In vivo and in vitro data revealed that treatment with mushroom polysaccharides displayed an anti-hyperglycemic effect by inhibiting glucose absorption efficacy, enhancing pancreatic β-cell mass, and increasing insulin-signaling pathways. Mushroom terpenoids act as inhibitors of α-glucosidase and as insulin sensitizers through activation of PPARγ in order to reduce hyperglycemia in animal models of diabetes. In conclusion, mushroom polysaccharides and terpenoids can effectively ameliorate hyperglycemia by various mechanisms and can be used as supportive candidates for prevention and control of diabetes in the future.