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dietary restriction to accompany the aging process in mice Can it be neuroprotective?

Neural Regeneration Research 2010年第10期5卷 789-795页

作者： Shougang Wei Xiaojuan He Shaojun Yun Shuhua Zhang Zhongxin Xiao School of Public Health and Family Medicine Capital Medical University Beijing 100069 China

BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE： The present study sought to：（1） determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and （2） examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN, TIME AND SETTING： The randomized controlled animal study. The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS： D-galactose （D-gal） was purchased from Beijing Chemical-Regent Company （Beijing, China）. Terminal transferase dUTP nick end labeling （TUNEL） detection kit was obtained from Roche, Germany. Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology （Nanjing, China）. Morris water maze （Friends Honesty Life Sciences Co. Ltd., Hong Kong, China） and Flow Cytometry （Coulter, USA） were used in this study.METHODS： A total of 40 male Institute of Cancer Research （lCR） mice, 3 months old, were equally and randomly divided into D-gal treatment, DR treatment, D-gal ＋ DR treatment and normal control groups, and were then randomly assigned to one of two feeding regimens： ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice. There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES： Animals＇ spatial learning and memory performance were tested in the Morris water maze. Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUN

关键词： dietary restriction brain aging D-galactose behavioral performance neuronal apoptosis oxidative stress neural regeneration

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Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging

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Journal of Molecular Cell Biology 2022年第3期14卷 36-47页

作者： Jing Wu Jiayu Liu Kalina Lapenta Reina Desrouleaux Min-Dian Li Xiaoyong Yang Department of Comparative Medicine Department of Cellular and Molecular Physiologyand Yale Center for Molecular and Systems MetabolismYale University School of MedicineNew HavenCT 06520USA School of Life Science and Technology Xi’an Jiaotong UniversityXi’an 710049China

O-linked N-acetyl-glucosamine glycosylation(O-GlcNAcylation)of intracellular proteins is a dynamic process broadly implicated in age-related disease,yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process.O-GlcNAc transferase(OGT)and the opposing enzyme O-GlcNAcase(OGA)control this nutrient-sensing protein modification in cells.Here,we show that global O-GlcNAc levels are increased in multiple tissues of aged mice.In aged liver,carbamoyl phosphate synthetase 1(CPS1)is among the most heavilyO-GlcNAcylated proteins.CPS1O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of theO-GlcNAc pathway.High glucose stimulates CPS1O-GlcNAcylation and inhibits CPS1 activity.Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting.Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction,implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity.

关键词： ageing O-GlcNAcylation urea cycle carbamoyl phosphate synthetase 1 calorie restriction posttranslational modification dietary restriction

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dietary Vitamin K restriction and Effectiveness of Vitamin K Antagonists Prescribed at the CNHU-HKM University Cardiology Clinic/BENIN

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Food and Nutrition Sciences 2023年第10期14卷 928-940页

作者： Clémence Germaine Metonnou Charles Jérôme Sossa Lamidhi Salami Rébécca Sabgohan Colette Azandjeme Camelle Mizehoun-Adossoda Virginie Mongbo Health Promotion Department Regional Institute of Public Health University of Abomey-Calavi Ouidah Benin Health Policy and Systems Department Regional Institute of Public Health University of Abomey-Calavi Abomey-Calavi Benin School of Nutrition-Dietetics Faculty of Health Sciences University of Abomey-Calavi Cotonou Benin

Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.

关键词： Antivitamin K dietary restriction Vitamin K Therapeutic Efficacy

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Variation of lifespan in multiple strains,and effects of dietary restriction and BmFoxO on lifespan in silkworm,Bombyx mori

Variation of lifespan in multiple strains,and effects of die...

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中国蚕学会第九届青年学术研讨会

作者： Jiangbo Song Dongmei Tang Zhiquan Li Xiaoling Tong Jianfei Zhang Minjin Han Hai Hu Cheng Lu Fangyin Dai State Key Laboratory of Silkworm Genome Biology College of BiotechnologySouthwest University Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry College of BiotechnologySouthwest University

Established animal models have accelerated our understanding of the mechanisms involved in lifespan determination.However,more experimental animals are required to clarify the complex mechanisms behind the phenomena of aging and lifespan.In this study,we reported the variation of lifespan in nine distinct silkworm strains.Lifespan correlated significantly with Bm FoxO gene expression in the representative silkworm strains tested（Xiafang,Dazao-N,and N4）.In general,the female silkworm was longer lived than the male of the same strain.dietary restriction extended the silkworm lifespan compared with that of silkworms fed ad libitum.The expression of Bm FoxO was significantly elevated in the dietary restriction group on day 3 of the 4 th instar and day 3 of the 5 th instar,suggesting that Bm FoxO contributes to dietary restriction-mediated lifespan extension.The RNA interference and overexpression of the Bm FoxO gene significantly shortened and extended the silkworm adulthood,respectively.In conclusion,our findings suggest that the silkworm might serve as a promising experimental animal to explore the complex biological mechanisms of lifespan determination.

关键词： silkworm lifespan dietary restriction BmFoxO experimental animal Gerotarget

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Aripiprazole extends C. elegans lifespan through a dopamine signaling mediated dietary restriction like mechanism

Aripiprazole extends C. elegans lifespan through a dopamine ...

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世界中医药学会联合会老年医学专业委员会2021年学术年...

作者： Yizhou Jiang ShengTao Hou Wenhua Zheng Centre of Reproduction Development & Aging and Institute of Translation Medicine Faculty of Health Sciences University of Macau Brain Research Centre and Department of Biology Southern University of Science and Technology

Although several longevity regulatory pathways have been identified in a wide variety of organisms, the role of the nervous system in lifespan regulation remains largely a mystery. Here, we report that the most widely used atypical antipsychotic drug aripiprazole could robustly extend lifespan and healthspan of C. elegans. The lifespan extension effect of aripiprazole is dependent on AMPK/FOXO-mediated dietary restriction(DR) mechanism. In addition, D2-like dopamine receptor DOP-2 and DOP-2-coupled Go protein GOA-1 are required in aripiprazole-mediated lifespan extension. DGK/PKC/PKD pathway, rather than c AMP/PKA pathway, acts as downstream of G protein and upstream of AMPK in aripiprazole-induced lifespan extension. This is the first study to reveal the lifespan extension effect of aripiprazole in lifespan regulation. As aripiprazole has good long-term safety and tolerability profile in patients, it may serve as a novel anti-aging drug and produce beneficial effects on human health and longevity. Moreover, the model of aripiprazole-mediated lifespan extension may provide a new direction for developing new anti-aging drugs.

关键词： Aripiprazole C. elegans longevity dietary restriction G-protein signaling

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Variation of lifespan in multiple strains,and effects of dietary restriction and BmFoxO on lifespan in silkworm,Bombyx mori

Variation of lifespan in multiple strains,and effects of die...

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中国蚕学会第十届青年学术研讨会

Established animal models have accelerated our understanding of the mechanisms involved in lifespan determination.However,more experimental animals are required to clarify the complex mechanisms behind the phenomena of aging and lifespan.In this study,we reported the variation of lifespan in nine distinct silkworm strains.Lifespan correlated significantly with BmFoxO gene expression in the representative silkworm strains tested（Xiafang,Dazao-N,and N4）.In general,the female silkworm was longer lived than the male of the same strain.dietary restriction extended the silkworm lifespan compared with that of silkworms fed ad libitum.The expression of BmFoxO was significantly elevated in the dietary restriction group on day 3 of the 4th instar and day 3 of the 5th instar,suggesting that BmFoxO contributes to dietary restriction-mediated lifespan extension.The RNA interference and overexpression of the BmFoxO gene significantly shortened and extended the silkworm adulthood,respectively.In conclusion,our findings suggest that the silkworm might serve as a promising experimental animal to explore the complex biological mechanisms of lifespan determination.

关键词： BmFoxO Gerotarget dietary restriction experimental animal lifespan silkworm

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Role of mitophagy in the hallmarks of aging

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The Journal of Biomedical Research 2023年第1期37卷 1-14页

作者： Jie Wen Tingyu Pan Hongyan Li Haixia Fan Jinhua Liu Zhiyou Cai Bin Zhao Department and Institute of Neurology Guangdong Medical UniversityZhanjiangGuangdong 524001China Guangdong Key Laboratory of Aging-related Cardiac and Cerebral Diseases ZhanjiangGuangdong 524001China Chongqing Key Laboratory of Neurodegenerative Diseases Chongqing 400013China Department of Neurology Chongqing General HospitalChongqing 400013China Department of Neurology the Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China Chongqing Medical University Chongqing 400042China

Aging, subjected to scientific scrutiny, is extensively defined as a time-dependent decline in functions that involves the majority of organisms. The time-dependent accretion of cellular lesions is generally a universal trigger of aging, while mitochondrial dysfunction is a sign of aging. Dysfunctional mitochondria are identified and removed by mitophagy, a selective form of macroautophagy. Increased mitochondrial damage resulting from reduced biogenesis and clearance may promote the aging process. The primary purpose of this paper is to illustrate in detail the effects of mitophagy on aging and emphasize the associations between mitophagy and other signs of aging, including dietary restriction, telomere shortening, epigenetic alterations, and protein imbalance.The evidence regarding the effects of these elements on aging is still limited. And although the understanding of relationship between mitophagy and aging has been long-awaited, to analyze details of such a relationship remains the main challenge in aging studies.

关键词： mitophagy aging dietary restriction telomere shortening epigenetic alterations protein imbalance

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Future foods,dietary factors and healthspan

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未来食品学报(英文) 2023年第2期3卷 75-98页

作者： Kaiqiang Li Chong Wang Yanbo Wang Linglin Fu Nianshu Zhang Food Safety Key Laboratory of Zhejiang Province School of Food Science and BiotechnologyZhejiang Gongshang UniversityHangzhou 310018China Department of Biochemistry University of CambridgeCambridge CB12GAUK

Ageing is a universal decline of physiological functions accompanied by an increase in risks of developing morbidity,diseases,and death.Calorie restriction(CR)without malnutrition has been shown to improve lifespan from simple model organisms to mammals,and extensive research over the past decades have identified several universally conserved signalling pathways by which CR regulates lifespan.More recently,emerging evidence has suggested that modulation of intake levels of macronutrients and micronutrients can also impact healthspan and lifespan in model organisms.These findings propose potentially promising and cost-effective approaches to promote healthy ageing and longevity in humans through personalised nutrition.In this review,we summarise the mechanisms by which CR promotes healthspan and longevity,focusing on the mitochondrial reactive oxygen species(ROS)and several universally conserved geroprotective nutrient-sensing pathways(insulin/insulin-like growth factor(IGF-1),AMP-activated protein kinase(AMPK),mTOR).We further discuss the accumulating data supporting that changes in dietary pattern,levels of nutrient intake(both macronutrient and micronutrient)and functional foods can impact healthspan through acting on the key components of nutrient-sensing and immunoprotective pathways,providing fundamental support for future research and development of anti-ageing diets and dietary regimes.

关键词： Lifespan dietary restriction Nutrient Immunity Ageing Longevity

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Why does caloric restriction increase life and healthspan? The ‘clean cupboards’ hypothesis

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National Science Review 2020年第7期7卷 1153-1156页

作者： John R.Speakman State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Institute of Biological and EnvironmentalSciences University of Aberdeen CAS Center of Excellence in Animal Evolution and Genetics Kunming Institute of Zoology Chinese Academy of Sciences

The disposable soma hypothesis explanation of the effects of caloric restriction(CR) on lifespan fails to explain why CR generates negative impacts alongside the positive effects and does not work in all species. I pr... 详细信息

关键词： SHORT-TERM CALORIE dietary restriction PROTEIN restriction GRADED-LEVELS LONGEVITY SURVIVAL IMPACT RETARDATION EVOLUTION RODENTS

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Lifespan Modulation in Mice and the Confounding Effects of Genetic Background

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Journal of Genetics and Genomics 2014年第9期41卷 497-503页

作者： Lorna Mulvey Amy Sinclair Colin Selman Institute of Biodiversity Animal Health and Comparative MedicineCollege of MedicineVeterinary and Life SciencesGraham Kerr BuildingUniversity of Glasgow

We are currently in the midst of a revolution in ageing research, with several dietary, genetic and pharmacological interventions now known to modulate ageing in model organisms. Excitingly, these interventions also appear to have beneficial effects on late-life health. For example, dietary restriction （DR） has been shown to slow the incidence of age-associated cardiovascular disease, metabolic disease, cancer and brain ageing in non-human primates and has been shown to improve a range of health indices in humans. While the idea thai DR＇s ability to extend lifespan is often thought of as being universal, studies in a range of organisms, including yeast, mice and monkeys, suggest that this may not actually be the case. The precise reasons underlying these differential effects of DR on lifespan are currently unclear, but genetic background may be an important factor in how an individual responds to DR. Similarly, recent findings also suggest that the responsiveness of mice to specific genetic or pharmacological interventions that modulate ageing may again be influenced by genetic background. Consequently, while there is a clear driver to develop interventions to improve late-life health and vitality, under- standing precisely how these act in response to particular genotypes is critical if we are to translate these findings to humans. We will consider of the role of genetic background in the efficacy of various lifespan interventions and discuss potential routes of utilising genetic heterogeneity to further understand how particular interventions modulate lifespan and healthspan.

关键词： Ageing dietary restriction Genotype Longevity

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