Yasuhisa Ano

• Ph.D
• Dupty Manager at Japan Agency for Medical Research and Development

Background Disorders associated with mental health significantly impact disability-adjusted life year values and represent an ongoing problem in stressed societies. Worsening mental health also affects cognitive function and quality of life. Increasing attention has thus been attracted to preventive measures for mental and brain health in daily lif...

Objective: This study aimed to investigate the effects of a long-term intervention with β-lactolin, a tetrapeptide (sequence: glycine-threonine-tryptophan-tyrosine) derived from milk, on cognitive performance in individuals with mild cognitive impairment (MCI). Methods: A randomized, double-blind, placebo-controlled trial was conducted. We recru...

Mental disorders have become one of the most burdensome health concerns. We have previously demonstrated that whey-derived β-lactolin (glycine–thereonine–tryptophan–tyrosine tetrapeptide) activates dopaminergic systems and improves psychiatric function in rodents. However, the effects of β-lactolin on human mood states have not been investigated. T...

Background Disorders associated with mental health significantly impact disability-adjusted life year values and represent a social problem in stressed societies. Worsening mental health also affects cognitive functions and quality of life. To address these issues, increasing attention is attracted to preventive measures vis-à-vis mental and brain...

in Japanese] Fullsize Image

With the aging of society, brain health issues that arise in the elderly have become a major social issue, attracting attention in relation to both prevention and health promotion in daily life. Recently, epidemiological investigations of Japanese subjects have shown that intake of milk and dairy products reduces the risk of dementia, and preclinic...

Matured hop bitter acids (MHBA), produced by aging the hops used to make beer, activate the vagus nerve via bitter taste receptors and improve depression and cognitive function in mice. However, researchers have not investigated their effects on human autonomic nerves. This crossover study aimed to investigate the association between MHBA and the v...

Mitochondrial dysfunctions are a key hallmark of Alzheimer’s disease (AD). β‐Lactolin, a whey‐derived glycine–threonine–tryptophan–tyrosine tetrapeptide, has been previously reported to prevent AD‐like pathologies in an 5×FAD mouse model via regulation of microglial functions. However, the direct effect of β‐lactolin on neuronal cells and neuronal...

Ag, Cu, Zn, Ti, and Au nanoparticles show enhanced photocatalytic properties. Efficient indoor disinfection strategies are imperative to manage the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Virucidal agents, such as ethanol, sodium hypochlorite, 222-nm UV light, and electrolyzed water inactivate SARS-CoV-2 in indoor env...

Maintenance and improvement of cognitive function and mood is important in an aging society. Preventive approaches, including diets used in daily life have received increasing attention in recent times. Clinical trials and preclinical studies have shown that hop bitter acids, which represent the bitter ingredients in beer, activate the bitter taste...

Neurodegenerative diseases involving pathological tau protein aggregation are collectively known as tauopathies and include Alzheimer's disease and Pick's disease. Recent studies show that the intake of tryptophan-tyrosine (Trp-Tyr)-related β-lactopeptides, including β-lactolin, attenuates cognitive decline in the elderly and prevents the amyloid p...

Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). β‐Lactolin, a whey‐derived glycine–threonine–tryptophan–tyrosine tetrapeptide, has been previously reported to prevent AD‐like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of β‐lactolin on neuronal cells and neuronal mit...

Context Epidemiological studies have shown that consumption of dairy products reduces the risk of dementia and cognitive decline in older individuals. Tryptophan-tyrosine-related β-lactopeptides and their representative β-lactolin of glycine-threonine-tryptophan-tyrosine tetra-peptide have been identified as agents in dairy products, which improve...

This study aimed to investigate the effect of non-alcoholic beer containing matured hop bitter acids on mood states among healthy adults older than 20 years. This study was an open-label longitudinal intervention design in which each participant served as their control. For three weeks, we evaluated the effect of non-alcoholic beer containing 35 mg...

With the rapid increase in aging populations worldwide, there has been an increase in demand for preventive and therapeutic measures for age-related cognitive decline and dementia. Epidemiological studies show that consumption of dairy products reduces the risk for cognitive decline and dementia in the elderly. We have previously demonstrated in ra...

The simultaneous accumulation of multiple pathological proteins, such as hyperphosphorylated tau (hp-tau) and phosphorylated α-synuclein (p-αSyn), has been reported in the brains of patients with various neurodegenerative diseases. We previously demonstrated that hp-tau-dependent p-αSyn accumulation was associated with the activation of GSK-3β in t...

Objectives Due to the rapid aging of society, the prevention of age-related cognitive decline and dementia has gained increasing attention. Recent epidemiological investigations have shown that the consumption of dairy products reduces the risk of dementia in older adults. β-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactopeptide, activates the dopam...

Background Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a Gly–Thr–Trp–Tyr lacto-tetrapeptide rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents...

Featured Application β-lactolin has protective effects on reactive astrocytes and mediates dopamine metabolism; it might thus aid in improving memory. Abstract Astrocytes are known to regulate normal brain function. Monoamine oxidase B (MAO-B), an enzyme highly expressed in astrocytes, metabolizes dopamine (DA) and induces reactive oxygen species...

Epidemiological studies have reported that consumption of dairy products rich in β-lactolin is beneficial for cognitive decline among elderly individuals. Although previous studies have shown that β-lactolin supplementation improves memory function and attention in healthy adults, the mechanism through which β-lactolin affects human brain function...

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption wit...

The prevention of age-related cognitive decline and dementia is becoming a high priority because of the rapid growth of aging populations. We have previously shown that hop bitter acids such as iso-α-acids (IAAs) and matured hop bitter acids (MHBAs) activate the vagus nerve and improve memory impairment. Moreover, supplements with MHBAs were shown...

Matured hop bitter acids (MHBA) are bitter acid oxides derived from hops, widely consumed as food ingredients to add bitterness and flavor in beers. Previous studies have suggested a potential gut-brain mechanism in which MHBA simulates enteroendocrine cells to produce cholecystokinin (CCK), a gastrointestinal hormone which activates autonomic nerv...

The number of elderly individuals with age-related cognitive decline or dementia is rapidly increasing. Dairy product consumption, including β-lactolin, is beneficial for their cognitive function. The underlying mechanism of β-lactolin's effects on human brain activity is yet to be investigated. We examined the β-lactolin effects on human cerebral...

Abstract Neurodegenerative diseases are characterized by the accumulation of specific phosphorylated protein aggregates in the brain, such as hyperphosphorylated tau (hp-tau) in tauopathies and phosphorylated α-synuclein (p-αSyn) in α-synucleinopathies. The simultaneous accumulation of different proteins is a common event in many neurodegenerative...

Introduction With rapid increase of aging worldwide, the number of people suffering from cognitive decline and dementia has been rapidly increasing. Numerous epidemiological and clinical studies have shown that consumption of dairy products have beneficial effects on cognitive decline and dementia in elderly. Our previous demonstration using pharma...

Background Prevention of age-related cognitive decline and depression is becoming urgent because of rapid growing aging populations. Effects of vagal nerve activation on brain function by food ingredients are inadequately investigated; matured hop bitter acid (MHBA) administration reportedly improves cognitive function and depression via vagal nerv...

Background Alzheimer’s disease (AD) is a neurodegenerative disorder histopathologically characterized by the accumulation of amyloid β (Aβ) peptides and inflammation associated with activated microglia. These features are well investigated in the central nervous system using AD-model mice; however, peripheral inflammation in these mice has not been...

Distillation remnants of Shochu, a traditional Japanese liquorare fed to livestock, but their effects on livestock health have not been investigated. Here, we investigated the effects of these remnants on pig stress and pork quality (N = 6 / group). The remnants reduced plasma cortisol (17.94 ± 0.92 [control] and 10.59 ± 1.28 [sample]) and increase...

Dementia and cognitive decline are global public health problems. Moderate consumption of alcoholic beverages reduces the risk of dementia and cognitive decline. For instance, resveratrol, a polyphenolic compound found in red wine, has been well studied and reported to prevent dementia and cognitive decline. However, the effects of specific beer co...

Dementia and cognitive decline have become worldwide public health problems. We have previously reported that a whey-derived glycine―threonine―tryptophan―tyrosine peptide, β-lactolin, improves hippocampus-dependent memory functions in mice. The supplementation with a whey digest rich in β-lactolin improves memory retrieval and executive function in...

The prevention of age-related memory decline and dementia has been becoming a high priority because of the rapid growth in aging populations. Accumulating epidemiological and clinical studies indicate that intake of fermented dairy products rich in β-lactolin improves memory retrieval and executive function and attenuates cognitive decline in the e...

This chapter focuses on mouse models of Alzheimer’s disease (AD), especially the 5xFAD line. 5xFAD mice exhibit severe amyloid-β deposition at 2 months of age and cognitive impairment by 3 months of age. Microglial activation and neuroinflammation are induced in 5xFAD mice, similar to the human AD pathologies. The effects of pharmacological agents...

The present study aimed to investigate the effects of matured hop bitter acids (MHBAs) on human cognition, mental fatigue, and mood state. In this randomized double-blind placebo-controlled study, 60 healthy adults (age 45–64 years) with self-awareness of cognitive decline were randomly divided into 2 groups and received either orally administered...

The number of patients with mental illnesses, including depression, is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. Consequently, corrective measures, such as diet-based treatment for diseases, are receiving great attention. We previously showed that β-lactolin, a β-lactopeptide of glycine-threonin...

Scope: Peptides containing tryptophan-tyrosine sequences, including the lacto-tetrapeptide glycine-threonine-tryptophan-tyrosine (GTWY) and β-lactolin, from β-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we...

Aim: Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso-α-acids (IAAs), the hop-derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of I...

The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine–histidine (LH) dipeptide suppres...

Prion diseases are a group of transmissible fatal neurodegenerative disorders. Neuropatho- logical features of prion diseases include neuroinflammation featuring the infiltration of activated microglia in affected brain areas as well as the accumulation of an abnormal isoform of the cellular prion protein and neuronal loss. Recent studies have eluc...

Rationale Cognitive decline and dementia are major concerns in today’s aging society. As limited treatments are available, measures to prevent cognitive decline and dementia are needed. We previously demonstrated that matured hop bitter acids (MHBA), bitter components of beer, increase norepinephrine in the hippocampus and improve memory in amnesia...

Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan–tyrosine (WY) and tryptophan–methionine (WM) pept...

An increase in the aging population, has spurred recent efforts to identify diet and lifestyle changes that help prevent cognitive decline. Several epidemiological investigations and clinical studies have indicated that consuming fermented dairy products prevents cognitive decline. Some peptides from whey including β-lactolin improve memory impairm...

Dementia and cognitive decline have become public health issues worldwide and life-style-related diseases and obesity have recently been reported as key risk factors. We have recently demonstrated that short-term administration of iso-α-acids (IAAs), hop-derived bitter components of beer, improves spatial and object recognition memory. However, the...

The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer's pathology in mous...

Epidemiological reports showed that consumptions of fermented dairy products are beneficial for cognitive decline in elderly. Our previous preclinical studies have demonstrated that intakes of whey peptide rich in the β-lactolin [β-lactopeptide of glycine-thereonine-tryptophan-tyrosine (GTWY)] improve memory and attention by regulating monoamine sy...

Dementia and cognitive decline have become worldwide health problems due to rapid growth of the aged population in many countries. We previously demonstrated that single or short-term administration of iso-α-acids, hop-derived bitter acids in beer, improves the spatial memory of scopolamine-induced amnesia model mice in the Y-maze and enhances nove...

Microglia, a type of immune cell in the central nervous system, are involved in inflammation leading to neurodegenerative diseases. We previously identified oleamide from fermented dairy products as a neuroprotective compound suppressing microglial inflammation. Oleamide is an endocannabinoid and displays anti-inflammatory activity via the cannabin...

Epidemiological investigations have reported that the habit of drinking tea reduces the risk of developing a mental disorder, including anxiety disorder and depression. Theaflavins, black tea polyphenols, show antibacterial and anti-oxidative effects, but their effects on brain function, especially mental condition, have not been elucidated. The pr...

Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-α-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer’s pathology in a rodent model. On the other hand, the effects of iso-α-a...

Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of...

With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mou...

Weight and food/water consumption in aged mice. We fed C57BL/6J mice aged 7 weeks (young; n = 12) and 68 weeks (aged) diets containing 0% or 0.05% (w/w) IAA for 3 months (aged with dietary IAA, n = 10; aged without dietary IAA, n = 9). (A) Body weight was monitored every month. (B,C) Food (B) and water (C) consumption over 72 h. Data are presented...

Recent studies have demonstrated a close association between neural inflammation and development of mental illnesses, such as depression. Clinical trials have reported that treatment with non-steroidal anti-inflammatory drugs is associated with reduced risk of depression. Moreover, nutritional approaches for the prevention and management of depress...

Inflammation in the brain is associated with various disorders including Alzheimer’s disease and depression. Thus, inflammation has received increasing attention regarding preventive approaches to such disorders. Epidemiological investigations have reported that drinking tea reduces the risk of dementia and depression. Theaflavins, a polyphenol fou...

Prion diseases are a group of transmissible fatal neurodegenerative disorders. Neuropatho-logical features of prion diseases include neuroinflammation featuring the infiltration of activated rnicroglia in affected brain areas as well as the accumulation of an abnormal isoforrn ofthe cellular prion protein and neuronal loss. Recent studies have eluc...

Iso‐α‐acids (IAAs) are hop‐derived bitter acids of beer. Epidemiologic studies suggest that moderate alcohol consumption is beneficial for cognitive function, but they do not show the ingredients in alcoholic beverages. Previously, we reported that long‐term consumption of IAAs prevents inflammation and Alzheimer pathologies in mice, but their effe...

Some epidemiological studies revealed that the consumption of dairy products prevents cognitive decline in the elderly. We previously demonstrated that tryptophan-tyrosine (WY)-peptide rich in Camembert cheese suppresses microglial inflammation. In the present study, 7-week-old (young) and 68-week-old (aged) C57BL/6J mice were fed diet containing W...

Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer’s disease pathology in model mice. However, the effects of iso-α-acids on inflammation induced...

Cognitive decline and dementia are currently recognized as major problems in the aging population; however, there is still no promising treatment for these conditions. Previously, our group reported that iso-α-acids (IAAs), which are hop-derived bitter components present in beer, prevent inflammation and cognitive impairment in an Alzheimer's disea...

Improving and maintaining memory function is effective in preventing cognitive decline and dementia. Previously, we demonstrated that iso-α-acids, the hop-derived bitter components in beer, prevent cognitive impairment in an Alzheimer’s disease mouse model. In this report, we investigated the effects of matured hop bitter acids (MHBA) containing co...

Alongside the rapid growth in aging populations, prevention of age-related memory decline and dementia has become a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help to prevent cognitive decline; furthermore, intake of Camembert cheese prevents Alzheimer's pathology in model mice. To e...

The accumulation of specific phosphorylated protein aggregates in the brain is a hallmark of severe neurodegenerative disorders. Specifically, hyperphosphorylated tau (hp-tau) accumulates in Alzheimer disease, frontotemporal dementia with Parkinsonism linked to chromosome 17, and progressive supranuclear palsy; furthermore, phosphorylated α-synucle...

Background: Previous epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia. Enzymatic digestion of whey protein produces a whey peptide rich in tryptophan-tyrosine-related peptides which improve cognitive performance in mice. We evaluated the effects of whey peptides on cogniti...

Alongside the rapid population aging occurring worldwide, the prevention of age-related memory decline and dementia has become a high priority. Dairy products have many physiological effects owing to their contents of lactic acid bacteria and the fatty acids and peptides generated during their fermentation. In particular, several recent studies hav...

Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated re...

Background> Our group previously reported that iso-α-acids, bitter components in beer, display preventive effects against Alzheimer's pathology using 5xFAD model mice (Ano et al., 2017, J. Biol. Chem.). Long-term intakes of iso-α-acids before the onset of the pathology suppress microglial inflammation and prevent cognitive decline in the mice, howe...

Background> Microglia is specialized macrophage population in the brain, and excessive activated microglia by chronic stress, aging, and brain injury, produces inflammatory molecules and massive reactive oxygen spieces (ROS), which lead neurological disorder including depression and dementia. Previously, we identified oleamide from fermented dairy...

Tolerogenic dendritic cells (DCs) have the ability to induce regulatory T cells and play an important role in preventing chronic inflammatory and autoimmune diseases. We have identified a novel compound, 14-dehydroergosterol, from Koji, a Japanese traditional food material fermented with fungi. 14-dehydroergosterol is an ergosterol analogue with a...

Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferat...

Epidemiological studies suggest that moderate consumption of alcoholic beverages can reduce the risk of dementia . Recent work has demonstrated that intake of iso-α-acids, the bitter components in beer; prevent Alzheimer’s disease pathology by regulating microglial function. In a transgenic mouse model of Alzheimer’s disease, iso-α-acid intake led...

Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. T...

Despite the ever-increasing number of dementia patients worldwide, fundamental therapeutic approaches to treat this disease remain to be established. Preventive approaches such as diet, exercise and learning attract attention. Several epidemiological studies suggest that ingestion of fermented dairy products prevents cognitive decline in the elderl...

Infectious prion diseases include Kuru and its variant, Creutzfeldt-Jakob disease, in humans, scrapie in sheep, and bovine spongiform encephalopathy in cattle. In these diseases, the pathogenic prion protein (PrP Sc) enters the host through the gastrointestinal tract and migrates to the central nervous system, where PrP Sc induces characteristic pa...

The single-stranded RNA encephalomyocarditis virus (EMCV) can replicate in the central nervous system (CNS) and lead to prominent brain lesions in the stratum pyramidale hippocampus and the stratum granulosum cerebelli. Activated microglia cells infected by EMCV produce a massive burst of reactive oxygen species (ROS) via NADPH oxidase 2 (NOX2) act...

Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-α that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-patho...