According to the World Health Statistics 2016, the country with the longest longevity in the world is Japan, where average life expectancy at birth (ALEB) was 83.70-years old. This is supported by the World Fact Book 2016, in which the ALEB of Japanese people is 85.00-years old. That is the second longest in the world, following 89.50-years old in Monaco. Considering the population of Japan is more than four thousand times than that of Monaco, the ALEB of Japanese people is undoubtedly ranked at the top of the world. Immediately after the Second World War, the ALEB of Japanese people was low as compared with the international communities. It is assumed that the sharp decline in mortality rate is due to the rapid progress in advanced medicine, supported by the post-war economic growth, contributing to the steady increase of ALEB. In 2000, Tuljapurkar forecasted the future life expectancy of the G7 countries, suggesting that the ALEB of Japanese people may extend beyond the conventional predictions. According to the estimates, the ALEB of Japanese people will be 86.01-years old in 2020 and 90.91-years old in 2050. In any case, if such a trend continues, there is concern that the medical expenses will increase due to the healthcare demands of the elderly population. In this special feature, we are going to introduce the front line of “functional peptides that contribute to healthy longevity” and propose ways to stay healthy and live longer. All chapters are based on scientific evidence accumulated by each author and very exciting content is presented. We will be very pleased if all the reviews posted here are useful to readers interested in this research field.

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Recent advances and future perspectives in the health beneficial peptides derived from food proteins related to the ameliorative effect on cholesterol metabolism are described. The hypocholesterolemic milk peptides, soybean peptides, meat peptides, egg peptides, royal jelly peptides or fish peptides are mainly described in this chapter.
For example, lactostatin (IIAEK) is the first identified hypocholesterolemic pentapeptide derived from bovine milk β-lactoglobulin in rats by our group. Lactostatin inhibits intestinal cholesterol absorption in Caco-2 cells (model for human intestine) and rats accompanying a hypocholesterolemia. Lactostatin activates cholesterol 7a-hydroxylase (CYP7A1) gene expression of the rate-limiting enzyme for cholesterol degradation through a new regulatory pathway in the calcium-channel-related MAPK signaling in HepG2 cells (model for human liver). The effects of a crude type of soy protein hydrolysate with bound phospholipids (CSPHP) on cholesterol metabolism were compared with the effects of soy protein hydrolysate with bound phospholipids (SPHP), soy protein peptic hydrolysate (SPH) and casein. Serum and liver cholesterol levels were significantly decreased with CSPHP, SPHP and SPH feeding compared with casein feeding. Daily intake of only 3 g CSPHP for 3 months reduced both serum total cholesterol and LDL cholesterol levels of the hypercholesterolemic patients.
Soystatin (VAWWMY), with a high taurocholate binding activity derived from soybean glycinin, is the first identified inhibitory peptide of intestinal cholesterol absorption in rats. By an exhaustive screening by peptide array, soystatin could enhance its hypocholesterolemic activity. The peptide array technology will be able to promote progress in peptide research.
The cattle heart protein hydrolysate (HPH) ameliorates hypercholesterolemia accompanied by the suppression of cholesterol absorption in rats and Caco-2 cells. The cattle heart protein hydrolysate ultra-filtrate (HPHU, MW < ca. 1,000 Da peptides fraction) derived from HPH imparts a stronger hypocholesterolemic activity than HPH in rats.
To identify the hypocholesterolemic peptide derived from egg white protein (ovalbumin), CYP7A1 activated peptide has been screened. CYP7A1 mRNA levels significantly increased by GLWEK compared with the control. GLWEK, which we named ovocholestin, was identified as a CYP7A1 activated peptide derived from ovalbumin in HepG2 cells.
The cholesterol-lowering action induced by MRJP1 (Major Royal Jelly Protein) occurs because MRJP1 interacts with bile acids inducing a significant increase in fecal bile acid excretion and a tendency to increase fecal cholesterol excretion and also enhance the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ.

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In the present study, we identified and chemically synthesized two cationic peptides, Amyl-1-18 and BCBS-11, which are derived from rice and soybean proteins, respectively. These peptides had high isoelectric points, high positive net charges, and included multiple hydrophobic amino acids. Subsequently, we identified multiple functions of the two peptides, including antimicrobial, lipopolysaccharide-neutralizing, and angiogenic activities. We also examined their cytotoxic activities against mammalian red blood cells. Amyl-1-18 and BCBS-11 exhibited antimicrobial activity against Porphyromonas gingivalis, Streptococcus mutans, and Candida albicans. Membrane-depolarization assays and flow cytometric analyses showed that the antimicrobial properties of Amyl-1-18 and BCBS-11 against P. gingivalis and S. mutans were dependent on membrane-disrupting potential. In contrast, major antimicrobial activities of the two peptides against C. albicans were dependent on interactions with targets other than cell membranes. Furthermore, chromogenic Limulus amebocyte lysate assays showed that the two peptides (50% effective concentrations, EC₅₀; 0.22-0.31 µM) neutralize LPS with similar potency (EC₅₀: 0.11 µM) to that of polymyxin B. Moreover, tube-formation assays in human umbilical vein endothelial cells showed similar angiogenic activities of the two peptides as those following treatment with LL-37. The rate of hemolysis for Amyl-1-18 and BCBS-11 in the presence of 250-µM was less than 2%. These results demonstrate that cationic peptides from food proteins have potential as multifunctional ingredients for healthcare applications.

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Aging is an inevitable part of life for humans and is associated with a decline in the physical and functional capacity of tissues and organs. Cognitive dysfunction, in particular, has emerged as a major debilitating disorder associated with old age. Age-related learning and memory deficits are widely accepted to be caused by neuroinflammation and oxidative stress in the brain. High expression levels of neuroprotective factors such as neurotrophic factors and antioxidant enzymes could contribute to the maintenance of neurological function. There has been increasing interest in natural dietary bioactive compounds with potential neuroprotective and brain health benefits, including the prevention of cognitive impairment and dementia. Therapeutic modulation of the levels of neurotrophic factors is thus a promising treatment strategy for neurological and psychiatric disorders with dysregulated levels. Since initial cognition decline is believed to result from dysfunctional synaptic plasticity, the induction of neurotrophic factors such as BDNF and GDNF by dietary bioactive compounds appears to contribute to the prevention of the age-related cognition decline process. Phytochemicals and bioactive peptides have been demonstrated to possess a preventive effect on cognitive decline in different animal models and in human studies. This review is focused on the effects of dietary bioactive peptides on brain function as well as neurological function-related factors and on animal models for evaluating cognitive performance.

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During preparation of peptides by enzyme hydrolysis, fermentation, etc., modification of the peptide such as deamination, hydrolysis, condensation, etc. may occur. Among these, formation of pyroglutamyl peptide is frequently induced. The glutaminyl residue at amino terminal of peptide can be converted to a pyroglutamyl residue. The pyroglutamyl peptides frequently resist peptidase digestion and can be absorbed into the blood system after ingestion. These peptides exist at up to 15% in the enzymatic hydrolysates of food proteins. Some of them exert significant biological effects when ingested. PyroGlu-Gln (pEQ) shows a umami taste. pEL moderates hepatitis and colitis in animal models. In addition, pEL exerts anti-inflammatory activity in cell culture systems. More interestingly, pEL normalizes colitis-induced dysbiosis by oral administration at 0.1 mg/kg body weight. Other pyroglutamyl peptides such as pENI also improve colitis and dysbiosis in the same animal model. These pyroglutamyl peptides are also present in fermented foods such as Japanese rice wine, soy paste, and soy sauce. The present authors suggest that, not only functional food based on enzymatic hydrolysate of food proteins, but also daily intake of fermented foods can have an impact on human health and that decline in consumption of traditional fermented foods might be associated with the increase of chronic diseases.

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Peptides display diverse structural features in their amino acid composition. The structural diversity often causes a complexity of physiological functions and possible health-benefits. Some peptides elicit preventive effects against hypertension, others ameliorate hypercholesterolemia and atherosclerosis, etc. Irrespective of their health-benefits, limited studies on peptide absorption may prevent understanding their extensive physiological functions. This review, thus, focuses on the absorption behavior of bioactive peptides across the intestinal membrane into blood systems. In short, some di- and tripeptides are often susceptive to intestinal protease hydrolysis, and others could be transported in their intact form through the peptide transporter (PepT1). For oligo-peptide absorption, their transport ability seems to be lower than those of small peptides, and their transport route may involve passive paracellular pathways.

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Food texture dramatically changes during oral processing in the short time until swallowing. Liquid foods are swallowed immediately, but swallowing behavior is influenced by the rheological properties and amount of food. Solid foods are broken up by every chewing movement using the teeth and changed to small fragments. The fragments are mixed with saliva, and then a bolus is made prior to swallowing.
Once food is inserted in the mouth, we cannot see by the eye what happens inside. To monitor the natural oral processing of humans, a medical ultrasound imaging instrument is utilized as a safe and non-invasive method. I have applied four ultrasonography techniques; 1) B (brightness)-mode (most common ultrasound imaging) to observe different human tissues, 2) M (motion)-mode that draws movement of tissues placed on a selected line to analyze tongue movement, 3) D (Doppler)-mode to display distribution in flow properties of boli, and 4) E (elastrography)-mode to show relative elasticity of soft materials (foods and model tongue).
As ultrasound imaging is applicable for observation of every healthy subject, including elderly people, data would be applicable for textural design of care foods and suggestions for safe-feeding.
I here introduce our recent studies using ultrasonography: kinetics of the human tongue during oral processing of water, sol, soft and hard gels and the swallowing observed using M-mode; effects of water volume on the flow properties at the entrance of the esophagus analyzed by pulsed Doppler-mode; and the relative strain of soft gels on a model tongue analyzed by ultrasound elastography. Compression testing of soft gels using the model tongue could explain the method of natural oral processing ―compression between the tongue and hard palate or chewing using the teeth― selected by the human subjects.

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Bitterness-masking agents are compounds that reduce the unfavorable bitter taste of food ingredients or drugs. Here we propose a novel screening method employing peptide array analysis for their identification bitterness-masking agents. Daily intake of green tea is considered beneficial because of the health benefits of catechin, an important component. Epigallocatechin gallate (EGCG), a major green tea polyphenol, has a broad range of physiologically beneficial functions, but its bitterness is unappealing to humans. In the present study, EGCG-binding peptides, which are promising bitterness-masking agents of EGCG, were screened using an amino acid sequence of ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), a protein obtained from the industrial waste of green tea production. Five hundred and ninety-eight types of pentadecapeptide contained in the RuBisCO sequence were chemically synthesized in parallel using SPOT technology. Seven peptides in the peptide library were characterized as EGCG-binding using redox-cycle staining. Deletion analysis of the amino acid residues from the N- or C-termini of these peptides highlighted the central regions (from 2 to 15 amino acids in length) as contributing to this binding. Subsequent alanine scanning revealed a critical contribution of Lys or Arg residues for all peptides obtained in the present study. Moreover, roles of these basic amino acid residues in the binding to EGCG were clearly indicated by analysis using a dipeptide library comprising 361 types of dipeptide. The EGCG-binding peptides MHFRVLAKALR and FTGLKSTSAFPVTRK identified using peptide array analysis were evaluated for their potential bitterness-masking effects using a cell-based assay employing hTAS2R39, a human bitter taste receptor for EGCG. The EGCG-binding peptides suppressed activation of hTAS2R39, indicating a bitterness-masking effect. These results revealed that bitterness-masking effects can be predicted for bitter substance-binding peptides using peptide array analysis.

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Functional effects of Plantago lanceolata L. (Plantain) on animal health and quality were investigated using pigs and chickens. Feeding fresh plantain to pigs decreased their body weight and thickness of back fat, but on the other hand increased the grade of dressed carcass. Addition of 5% to 10% of dried Plantain to mixed feed for chickens also markedly decreased their body weight gain and fat accumulation in the abdominal cavity. However, content of polyunsaturated fatty acids in breast meat was significantly increased. Furthermore, the levels of essential fatty acids were elevated while the n-6/n-3 lipid ratio was significantly decreased. The plantain admixture to feed improved the shelf life of the chicken meat due to suppression of lipid peroxidation. Taste traits other than bitterness, such as scent, ‘umami’, sweetness, and richness of soup were more highly evaluated with chickens fed on plantain.
Since the plant has been used to produce anti-diabetic tea in Eastern Anatolia, a region of Turkey, we also investigated anti-metabolic syndrome effects of plantain when fed to male C57BL/6J mice. Supplementation in a high-fat diet did not affect food intake but significantly reduced serum free fatty acid and glucose levels. These findings and real time PCR analysis on gene expression suggested that Plantain exerts anti-metabolic syndrome effects. In addition, anti-alzheimer's effect of Plantain is suggested.
Plantain contains acteoside, catalpol, aucubin geniposidic acid and asperuloside as bioactive components which might be involved in its functional effects.

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Japanese restaurant cuisine is now prevalent in markets around the world, from large cities to small towns. Our research project develops a mobilities perspective to represent the transnational spread of Japanese cuisine. We emphasize that the organization of the Japanese culinary field is centered in global cities which are the hubs of the local networks through which ideas, producers and products flow. Non-Japanese ethnic networks are especially important in spreading Japanese cuisine in low-cost forms away from urban centers. Migrant Japanese entrepreneurs remain significant innovators, especially in global food cities such as New York.

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