Purpose: The "NAD World" (proposed by Professor Shin-Ichiro Imai of the University of Washington), in which the control of aging, lifespan, and metabolism is systemically integrated through NAD (nicotinamide adenine dinucleotide), has attracted worldwide attention and is being studied from various angles, however, there are few reports of clinical studies in humans. In this study, we investigate the changes in various biomarkers in humans after oral intake of nicotinamide mononucleotide (NMN), a precursor of NAD, and evaluate its clinical significance. Methods: Based on the approval to start the study at the ethics review, 17 postmenopausal women (mean age 55.0 years) without underlying diseases who agreed to participate in the study were subjects and received oral intake of 300 mg/day of pure NMN for eight weeks. The examination items included body measurements, basal metabolic rate, blood pressure, grip strength, glycation level (AF value), blood biochemical tests, various hormones, blood SIRT1 mRNA expression and NMN, NAD and NAM levels, immunological tests (aging, T cell subset including exhausted cells), and skin VAS (visual analog scale). Results were statistically analyzed and compared at zero and eight weeks (blood biochemistry tests were performed at four weeks to confirm safety). In addition, we asked the patients to keep a diary during the course of the study to monitor their NMN intake, their bodily sensation, and side effects. Results: One of the 17 subjects dropped out at the end of four weeks due to persistent mild headache. The results showed significant changes in NAM (nicotinamide/vitamin B3) from 45.2 to 164.7 (p < 0.001), adiponectin from 13.6 to 16.2 (p = 0.004), and skin VAS score (6/7 items, p < 0.001 to = 0.001) before and after intake. Significant differences were also observed for BMI, AF levels, platelets, HbA1c, HDL-C, amylase, DHEA-s, NAD, and narrowly defined regulatory T cells (p < 0.05 above). In addition, all subjects showed a positive bodily sensation with skin, sleep, and fatigue. There were no problems with subjective symptoms or laboratory data in the 16 who completed the study. Conclusion: NMN 300 mg/day orally for eight weeks showed no safety issues and favorable changes in many biomarkers, suggesting that NMN, a member of the NAD world, may be a promising nutritional material for aging and metabolic control in humans.

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Considering the importance of the low-density lipoprotein receptor-related protein 1 (LRP1) as the scavenger of harmful waste products from the brain, especially amyloid beta (Aβ), and as the mediator in a number of signal events, LRP1 is increasingly becoming the object of intensive researches. Alzheimer's disease (AD), as proved, is the result of the disordered Aβ intracerebral homeostasis, characterized by intensive Aβ accumulation in the brain, induced primarily by the Aβ disordered efflux from the brain, and not by its increased production. This elevated Aβ accumulation in the brain structures leads to the increase of the local oxidative stress with intensively harmful effects of the generated free radicals, especially hydroxyl radicals (*OHs). This condition is accompanied by severe oxidative damages of a number of vital brain structures, especially endothelial cell membranes. LRP1, at the level of blood-brain barrier (BBB) endothelial cells, initiated by Aβ binding to its ligand binding domains, especially domains II and IV, induces specific conformational changes in both receptor domains, which causes the onset of pulling forces that, starting from the point of Aβ binding to LRP1, spread along the receptor structure in both directions. Especially important is the spreading of these forces towards the abluminal membrane, their passing across this membrane and entering the receptor tail region and the compound structure of its molecules. The activation of these molecular systems leads to endocytosis, transcytosis, and exocytosis of Aβ bound to the receptor, into the capillary blood of the BBB. The drained Aβ travels further on by the blood stream, exits from the brain, and arrives at the positions of its degradation and elimination, liver, kidneys, spleen, and skin. Investigations have shown that generally, the expression of LRP1 in the BBB endothelial cell system declines during normal ageing, and especially in AD. It is evident that this phenomenon weakens the Aβ drainage from the brain. The actual question is what causes the LRP1 expression drop in these conditions, and if it is possible to slow down this drop. In this respect, this review paper intends to explain the problem of the LRP1 expression decline, and its possible increase, i.e., the retardation of the AD pathophysiological course.

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Accumulation of advanced glycation end products (AGEs) in the body due to glycative stress is a factor in the progression and development of aging and lifestyle-related diseases. Oxidation is one of the accelerators of glycative stress because it promotes the formation of AGEs. On the contrary, glycative stress suppression includes suppression of postprandial hyperglycemia, suppression of AGE generation, and degradation and excretion of AGEs. Various vegetables and herbs have already been reported to have antiglycative effects. In this study, for the purpose of verifying the usefulness of glycative stress suppression materials, we focused on eggplant as a vegetable that can be consumed as a familiar food, and verified its antiglycative effect and antioxidative effect. Seven commercial eggplant varieties were used as samples. Samples were tested for changes in effects among eggplant varieties and after, four types of cooking (baked, fried, boiled, and nukazuke [rice bran pickles]). In addition, the amounts of chlorogenic acid and anthocyanin, the major components of eggplant, were measured and their relationship to the antiglycative and antioxidative effects were verified. All eggplant varieties tested showed antiglycative and antioxidative effects. The difference between the varieties was 3.5-fold for antiglycation and 4.9-fold for antioxidative activity. The changes in the effects of eggplant after cooking were small for baked and fried eggplant, less than 5% change in antiglycation and less than 15% change in antioxidative activity. In contrast, after eggplant was boiled and nukazuke, the antiglycative and antioxidative effects decreased by more than 35% and 60%, respectively. It was estimated that the difference in the antiglycative and antioxidative effects of eggplant was largely influenced by the amount of chlorogenic acid. It was considered that the choice of cultivar and cooking method is important for the use of eggplant while focusing on glycative stress.

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Aim: Glycation is a non-enzymatic reaction between reducing sugars and proteins. It forms advanced glycation end products (AGEs) and is involved in multiple diseases. We have reported that strawberries are one of the plants that inhibit the formation of AGEs. It has been reported that water treated with ceramic chips (ceramic-treated water) enhanced the growth of agricultural crops. In this study, we examined the effect of ceramic-treated water on the food functionality of strawberries, especially the anti-glycative effect and antioxidant efficacy. Methods: Fourteen varieties of strawberry plants were cultivated using either normal water or ceramic-treated water, and harvested strawberries were sliced, dried, and ground. Extracts were prepared with hot water and introduced into the human serum albumin (HSA)-Glucose glycation model. Inhibitory effects on glycation were evaluated by measuring fluorescent AGEs, and antioxidative efficacy was measured by the DPPH method. Results: All the strawberry samples showed anti-glycative effects and antioxidant activity. There was no significant difference between the cultivation water in the paired t-test for either effect. However, one variety showed a significant increase in inhibition of AGEs formation, and 4 varieties showed a significant increase in antioxidant activity in the ceramic-treated water cultivation. No correlation between anti-glycative and antioxidative effects was found. Conclusion: In this study, we examined the effect of growing water on 14 strawberry varieties. Ceramic-treated water changed the feature of strawberries, but the change depends on the varieties. This indicates that the effect of ceramic-treated water may be limited to certain varieties. In addition, the lack of correlation between anti-glycative and antioxidative effects suggested that the substances contributing to each effect were different.

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The effects of a 60-minute hot yoga program twice a week for 12 weeks in healthy women who were aware of their lack of exercise were examined and compared with a control group. The analysis subjects were divided into two groups: a control group (19 subjects, age 43.6 ± 10.3 years, BMI 26.4 ± 0.8) and a hot yoga group (34 subjects, age 44.1 ± 9.5 years, BMI 25.7 ± 0.4), and the hot yoga practitioners were further divided into a wood stone floor group and a regular floor group (17 subjects each). Measurements after 12 weeks showed improvement in skin condition (water content, wrinkles, and texture), improvement in mental stress according to the SF-8 questionnaire, mild improvement in weight, body shape, and flexibility, decrease in HbA1c, and increase in expression of sirtuin gene SIRT6. No adverse events were noted. A comparison of regular and woodstone floors showed a greater improvement in SF-8 body score when using woodstone floors, and blood tests showed an avoidable decrease in RBC and Hb, a significant increase in total protein, and a mild increase in CPK, which was considered an advantage of the woodstone floors. In the present study, a 12-week hot yoga program conducted with potentially inactive women showed a wide variety of effects and increased SIRT6 expression as a factor involved in the mechanism of action. The results suggest that hot yoga, a combination of thermotherapy and yoga, is a safe health promotion method that increases sirtuin activity and enhances the efficiency of health promotion effects both mentally and physically.

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The bactericidal efficacy of stable sodium hypochlorite (s-SH, AirRish) was evaluated through in vitro testing against planktonic solutions of Staphylococcus aureus and Staphylococcus epidermidis. After an exposure time of 5 minutes viable colony forming units of both species fell below the limit of detection with both 100 ppm and 200 ppm s-SH, a greater than 6 log10 reduction (p ‹ 0.001). Additionally, the antimicrobial effect of s-SH was also examined in hand sanitization applications. In a 60s hand rub, 200 ppm s-SH achieved a 96% reduction in hand CFUs, of similar effect as a typical alcohol sanitizer (p = 0.28). s-SH maintained considerable bactericidal efficacy at the tested concentrations.

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Purpose: An open-level study with no control was conducted to confirm the changes in subjective and objective symptoms and safety of a food test product (INJUV) containing a rooster comb enzymatic degradation product that contains low molecular weight hyaluronic acid (HA) as a major component. Methods: From 25 healthy subjects who were aware of dry or eye fatigue, 12 subjects with severe symptoms (male: 6, female: 6, age: 37.8 ± 10.1 years) were selected as subjects. The subjects orally ingested INJUV for 4 weeks, and eye examinations and questionnaires were conducted before and after ingestion, and the results were compared. Results: Subjective symptoms that improved significantly were "eye dryness," "eye pain," "eye fatigue," and "eyelid heaviness." The nine items that improved significantly in the Anti-Aging QOL Common Questionnaire were "eye fatigue," "blurred vision," "eye pain," "stiff shoulders," "muscle pain/stiffness," "lethargy," "skin problems," "headache," and "dizziness." Tear layer breakdown time improved from 3.6 seconds to 5.5 seconds (p < 0.05), intraocular pressure (IOP) decreased from 13.0 mmHg to 11.7 mmHg (p < 0.01), and diastolic blood pressure decreased from 73.3 mmHg to 68.9 mmHg (p < 0.05). No adverse events were observed during the study period. Conclusion: Oral intake of INJUV was shown to be safe and improve ocular symptoms, quality of life and ocular surface, as well as lower IOP and diastolic blood pressure.

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Glycative stress-induced production and accumulation of advanced glycation end products (AGEs) in the body contribute to aging and the development of various diseases. N-phenacylthiazolium bromide (PTB) cleaves the α-diketone bond, which is the most common glycation end product in the body. PTB cleaves α-diketone bonds and cleaves cross-links associated with the formation of AGEs in glycated proteins (cleavage of AGE cross-linking; CAC). However, since glucospan, α-diketone, and lysine-dihydropyridinium-lysine are involved in the formation of protein cross-links by glycation, the usefulness of the cross-link cleavage effect must be verified using glycated proteins. Whereas, measurement of cleavage of glycated-protein cross-linking (CGPC) using glycated lysozyme as a model has been reported. In this study, CGPC and CAC of 12 substances contained in vegetables and herbs were measured to examine the possibility of degradation of protein cross-links polymerized by glycation. 12 substances were measured for CGPC and CAC, and a high positive correlation was observed between CGPC and CAC in 6 substances (50%), indicating that α diketone bond cleavage may be involved in the degradation of glycated protein cross-links. In contrast, only CGPC was observed for the three substances, and it was possible that they cleaved cross-links different from the α-diketone structure; the CGPC measurement had the potential to evaluate glycated protein cross-link cleavage actions other than α-dicarbonyl bond cleavage.

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