The process of aging, essentially a natural, complex, purposeful, multi-profile, and inevitable process in the life cycle of living beings, therefore also of humans, according to today's knowledge, is most likely based on a program located in the genome. As research shows, this process consists of two closely intertwined components, normal or physiological aging, and accelerated or pathological aging related to diseases. Life is essentially a conglomeration of more or less complex physiological and biochemical processes that are constantly taking place, and whose alteration or extinction leads to life's cessation and death. An inevitable phenomenon related to a large part of these processes is the generation of the so-called reactive oxygen metabolites (ROS, reactive oxygen species). These are molecular structures characterized by two fundamental properties, aggressiveness and destructiveness of molecular body structures, and signaling effects in the form of secondary messengers, which all have an impact on the mentioned processes. Among these, the oxidative destruction of exposed molecular structures, according to some of the latest findings, are particularly important for the process of programmed aging. Within the mentioned molecullar structures, there are two large transmembrane multiligand receptors, low-density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end products (RAGE), as well as three enzymes deoxyribonucleic acid cytosine methyltransferases (DNMTs). Among these molecules, exposed to ROS, are also two Sp1 and Sp3 transcription factors (Sp1 and Sp3 proteins), otherwise abundantly present in tissues and cells. ROS compounds by the strong activation of ERK1 (p42) and ERK2 (p44) mitogen activated protein kinases, as well as c-Jun NH2 terminal kinases, condition the transcription and expression of these two mentioned factors (Sp1 and Sp3), resulting in their strong effect on DNMTs promoters with pronounced transcription and formation of DNMTs proteins. As components of crucial importance in the epigenetics systems, DNMTs proteins condition methylation processes of DNA molecules (adding methyl group -CH3 to the molecules), generate the formation of 5-methyl cytosine (5mC) on template DNA chains, and decrease the transcription of methylated genes while shutting down their expression. Due to specific conditions related to LRP1 and RAGE promoters, these receptors have different reactions to DNMTs-induced methylation. LRP1 promoter methylation is fast and intense, and RAGE promoter methylation is extremely slowed down and reduced. The final effects of those two genes, or their receptors, are extremely different. Biochemical and physiological processes related to LRP1 gradually slow down and dampen, and processes related to RAGE become more and more expressive. Another group of processes related to epigenetics and programmed aging includes oxidative demethylation of 5mC DNA segments via ten-eleven translocases (TET), thymine DNA glycosylase (TDG) and base excision repair enzymes (BER). This second group of events is less efficient than the first group, and methylation obviously dominates. All these processes increasingly point to the crucial importance of the process of transcription of the genes shown earlier. Regenerating transcriptions under the strong control of Sp proteins, and their programs located in the genome, influence the maximum possible life span of individuals of a species. The aim of this study is to provide explanations of the role of the mentioned receptors in the programmed aging of living beings.

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Objective: Glycation is a non-enzymatic reaction in which reducing sugars and derived aldehydes bind to amino groups of proteins, leading to the formation of advanced glycation end products (AGEs). AGEs accumulate in tissues with aging, causing inflammation, discoloration, and functional deterioration, and are associated with the onset and progression of lifestyle-related diseases. This study investigated the glycative stress-alleviating effects of black soybeans. Methods: Seven commercially available black soybean varieties, one yellow soybean variety, 12 isoflavones, and cyanidin-3-glucoside (C3G) were used. Beans were hot-water-extracted at 80°C for 1 hour as whole-bean samples or separated into seed coats and cotyledons prior to extraction. Glycation inhibitory effects were evaluated using a human serum albumin (HSA)–glucose glycation model by measuring suppression of fluorescent AGE formation. Antioxidant activity was assessed by the DPPH method. Isoflavone and C3G contents were quantified by reversed-phase HPLC. In addition, α-glucosidase inhibitory activity and the effect of black bean intake on postprandial blood glucose levels were examined. Results: All soybean extracts inhibited fluorescent AGE formation, with black soybeans showing stronger effects than yellow soybeans. Among black soybeans, Kurosengoku exhibited the highest inhibition rate (85.3 ± 2.5%). Seed coat extracts showed significantly stronger anti-glycation activity than cotyledon extracts, with inhibition rates of up to 99.7 ± 0.28%. All black soybean varieties demonstrated antioxidant activity, with a maximum of 286.1 µmol Trolox equivalents /L (7.5 mg/mL solids). Isoflavones were more abundant in seed coats than cotyledons, while C3G was detected only in seed coats. Conclusion: Black soybeans exhibit both anti-glycation and antioxidant properties, suggesting their potential as a dietary strategy to alleviate glycative stress.

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In recent years, the prevalence of metabolic syndrome in Japan has increased due to the Westernization of dietary habits and decreased physical activity. The progression of fatty liver to MASLD (metabolic dysfunction-associated steatotic liver disease) and its inflammatory and fibrotic variant, MASH (metabolic dysfunction-associated steatohepatitis), has become a growing health concern. Excessive or inappropriate intake of carbohydrates and lipids causes rapid postprandial hyperglycemia “blood glucose spikes”, which in turn induces the production of various sugar- and lipid-derived aldehydes. We refer to this phenomenon as the “aldehyde spark”. These short-chain aldehydes not only damage vascular endothelial cells but also modify proteins in pancreatic β-cells and hepatocytes, resulting in the formation of advanced glycation end-products (AGEs) and impaired protein function. Glycative stress (GS) describes a pathological condition in which the body is overloaded with aldehydes. Metabolism of excess aldehydes by dehydrogenases (e.g., ALDH, GAPDH) requires NAD+, thereby reducing the NAD+/NADH ratio. NAD+ depletion impairs β-oxidation of lipid droplets in hepatocytes, while mitochondrial dysfunction in the TCA cycle leads to the overproduction of fumaric acid, a metabolite capable of modifying proteins. Furthermore, AGEs bind to receptors for AGEs (RAGE) expressed on macrophages and Kupffer cells, which subsequently induces chronic inflammation. This cascade is thought to contribute significantly to the transition from simple steatosis to steatohepatitis. This report proposes a preventive strategy centered on GS care. Specifically, we advocate a three-pillar intervention consisting of nutritional education, physical activity promotion, and behavioral support to suppress postprandial glucose and aldehyde spikes. In addition, supplementation with NAD+ precursors and correction of protein insufficiency may help enhance the aldehyde-trapping capacity of amino acids, promote insulin biosynthesis, and improve insulin resistance. We hope that such comprehensive metabolic approaches will help prevent the progression of steatohepatitis and support liver metabolic health.

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