Glycative stress is a concept that refers to a state in which aldehydes, mainly derived from reducing sugars, lipids, and alcohol are excessively produced in the body, leading to aging and age-related diseases. Since the persistence of postprandial hyperglycemia contributes to increased glycative stress, understanding the impact of dietary carbohydrates on postprandial blood glucose levels is crucial for counting glycative stress. Many confectioneries, being very sweet and rich in sugar and lipids, are habitually consumed as snacks or desserts with beverages. This study examined the effects of Yokan (a type of Japanese confectionery) on blood glucose levels when ingested with a beverage, aiming to evaluate the impact of consuming Japanese confectionery on glycative stress. The subjects were 21 healthy men and women aged 20-30 years who provided written consent to participate in the study. They did not meet any exclusion criteria and were selected based on selection criteria in a pre-test involving the ingestion of glucose water (reference food). The test foods included glucose water (test food A) as the reference, and Yokan with various beverages: water (B), green tea 1 (C), green tea 2 (D), guava leaf tea (E), and coffee (F). Each contained 50g of carbohydrates, and the blood glucose level changes were monitored. The test was conducted using a FreeStyle Libre Pro, which measured the glucose concentration in the interstitial fluid of the skin tissue as an indicator of blood glucose level. Blood glucose levels were collected before consuming the test food multiple times over the next 120 minutes. The blood glucose change, maximum blood glucose concentration (ΔCmax), and incremental area under curve (iAUC) were measured and evaluated. The iAUC and ΔCmax after consuming the test foods B to F were lower compared to test food A. No differences in iAUC and ΔCmax were observed between the different beverages. The subjects were divided into three groups (H, M, L) based on the highest ΔCmax after consuming test food B, and differences in iAUC and ΔCmax after consuming the test foods were analyzed as a subclass analysis. In group H, the ΔCmax was smaller after consuming test food C compared to A, B, D, and E. The iAUC in group H was smaller after consuming test foods B, C, and F than A. Consuming Yokan, regardless of the type of beverage, resulted in a smaller increase in postprandial blood glucose levels compared to consuming glucose water. In group H, the suppression of blood glucose rise differed depending on the type of beverage consumed with Yokan, and beverages (C and F) had a strong effect on suppressing the rise in ΔCmax. Consuming Yokan with a beverage may be an effective method to reduce glycative stress caused by glucose spikes.

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Objectives: Research on neurocognitive disorder, which is a significant barrier against a healthy life span, has been intensively conducted in this aging society. Problems, however, are not yet solved for treatments. The purpose of the present study is to evaluate safety and clinical efficacy on intranasal administration of stem cell secretome (stem cell supernatant/exosome) in patients with Alzheimer’s disease, the primary disease which causes cognitive disorders. Furthermore, this study explores future prospects of stem cell secretome therapy. Methods: Research participants were patients with Alzheimer's disease who scored approximately 10–20 points of 30 (the full score) on the Hasegawa's dementia scale-Revised (HDS-R). Among 18 initial participants, 5 participants dropped out because of aggravation in pre-existing diseases and other factors. The number of final analysis participants was 13. Adipose-derived mesenchymal stem cell secretome was prescribed with intranasal administration at 3 vials/week for 8 weeks. (one vial included exosome: approximately 1×10 ⁸, HGF, which is one of major hepatocyte growth factors: 1.2 × 10 ⁵ pg, and multiple high-concentrated bioactive substances). Check list items were HDS-R, blood pressure, pulse, blood biochemistry tests, measurements of hormones, and MCI screening test (measurement tests of 9 types of proteins, which are related to Alzheimer’s disease). Evaluations were conducted before and after treatments to confirm safety of nasal drip therapy and to examine alternations in HDS-R scores, blood tests, and alternations of each protein in MCI screening test. Results: Scores of HDS-R were significantly improved: mean values 15.6 ± 1.0 → 17.5 ± 1.4 (p = 0.030). More obvious significant differences were recognized in a subclass analysis of mild and moderate cases for patients who had around 15-20 scores in HDS-R: 17.2 ± 0.6 → 20.0 ± 0.8 (p = 0.006). Among blood tests, significant differences with a significant level of 1% or less than 1% were shown in platelet (decrease), albumin/globulin ratio (increase) and LDL cholesterol/HDL cholesterol ratio (decrease). MIC screening test provided, among 9 types of proteins, a significant increase in apolipoprotein A-1, which is related to amyloid β excretion: 131.6 ± 6.1 → 150.3 ± 7.0 (p = 0.010). No adverse events considered to be related to treatments were observed in 13 research participants during the treatments. Conclusion: Intranasal administration of adipose-derived mesenchymal stem cell secretome for 8 weeks observed no safety problems and provided significant increases in scores of the Hasegawa's dementia scale-Revised (HDS-R). Therapy of intranasal administration of stem cell secretome (stem cell culture supernatant/exosome) is a safe and simple method, which can be performed at home. Judging from improvement effectiveness on cognitive functions, its possibility as a new treatment was suggested for Alzheimer’s cognitive disorder. Further studies are required to solve multiple problems and tasks, establish credible scientific evidence and organize environments for safety. It is our hope that stem cell secretome treatments will be implemented and widely introduced to clinical settings in an appropriate manner.

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Through the mediation of the gut-brain axis, sleep quality has a bidirectional effect on the gut microbiota. Using fecal T-RFLP flora analysis, we have found that improving sleep quality leads to changes in the gut microbiota. In particular, we observed an increase in short-chain fatty acid (SCFA)-producing bacteria such as Bacteroidota, Oscillospiraceae, and Lachnospiraceae. The microbiota of persons with poor "sleep quality" is similar to the pattern of dementia patients, and may approach the pattern of healthy people as "sleep quality" improves. In this report, we picked up major bacteria that are expected to be related to sleep quality and reviewed the literature. It seems important to avoid dysbiosis and maintain the dominance of SCFA-producing bacteria in order to maintain good "sleep quality" and hopefully prevent the progression of dementia.

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Our research center started a promoting-walking activity program in the Yurin district of Kyoto in 2008, where 40–50 participants living an independent life (mean age: 75 years) were lent a pedometer, and an anti-aging medical checkup was conducted annually with functional age assessments: muscle, vascular, neural, hormone, and bone age (a project of Kenpo Juku). Students (22–23 years) visited them once a month to collect information of participants’ walking and also to encourage them to walk in face-to-face meetings. The number of average steps in members (7,000–8,000 steps/day) was approximately twice as many as that of persons close to their age. The comparative study regarding self-supported degrees (persons of independence: Kenpo Juku members, persons requiring assistance, and persons requiring nursing care) in 2010 exhibited that persons of higher degrees of independence stayed young in neural age and maintained cognitive functions. A report on amyloid β 40/42 ratio (2019) substantiated this. It was suggested that a third had a low ratio and would maintain amyloid β clearance. A survey conducted from 2012 to 2014 revealed that the participants had low skin autofluorescence and were a group with weak glycative stress. Glycative stress refers to a condition in which excess aldehydes are easily produced in the body, making body proteins highly susceptible to conversion into advanced glycation endoproducts (AGEs). Trends in data between 2008–2022 of the long-term observation cases were shown regarding functional ages. Survey on medical expenses (2023) indicated that medical expenses of Kenpo Juku members were mostly lower than the national average. The face-to-face encouragement from the students increased the members' motivation to continue walking and led to the long-term continuation of the exercise habit, which may help prevent the aging of functional age.

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