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Aging and aging-related diseases:from molecular mechanisms to interventions and treatments

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Signal Transduction and Targeted Therapy 2023年第1期8卷 77-116页

作者： Jun Guo Xiuqing Huang Lin Dou Mingjing Yan Tao Shen Weiqing Tang Jian Li The Key Laboratory of geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China

Aging is a gradual and irreversible pathophysiological *** presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases,including neurodegenerative diseases,cardiovascular diseases,metabolic diseases,musculoskeletal diseases,and immune system *** the development of modern medicine has promoted human health and greatly extended life expectancy,with the aging of society,a variety of chronic diseases have gradually become the most important causes of disability and death in elderly *** research on aging focuses on elucidating how various endogenous and exogenous stresses(such as genomic instability,telomere dysfunction,epigenetic alterations,loss of proteostasis,compromise of autophagy,mitochondrial dysfunction,cellular senescence,stem cell exhaustion,altered intercellular communication,deregulated nutrient sensing)participate in the regulation of ***,thorough research on the pathogenesis of aging to identify interventions that promote health and longevity(such as caloric restriction,microbiota transplantation,and nutritional intervention)and clinical treatment methods for aging-related diseases(depletion of senescent cells,stem cell therapy,antioxidative and anti-inflammatory treatments,and hormone replacement therapy)could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

关键词： diseases alterations aging

Ethnic Differences in Preterm Birth Risks for Pregnant Women with Thyroid Dysfunction or Autoimmunity:A Meta-analysis

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Biomedical and Environmental Sciences 2016年第10期29卷 724-733页

作者： LI Min WANG Shao Wei WU Feng Li SHI Jin YU Pu Lin PENG Xiu Ling SUN Liang Department of Gynecology and Obstetrics Beijing HospitalNational Center of Gerontology Institute of geriatrics Beijing HospitalNational Center of Gerontology Department of Gynecology and Obstetrics Morin Dawa Daur Autonomous Banner Hospital

Objective Abnormal maternal thyroid function is associated with preterm ***,this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting *** study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic *** Relevant studies were identified through searches of MEDLINE,Excerpta Medica,Wan Fang,China Biological Medicine disc,and China National Knowledge Infrastructure from inception to June 15,*** articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were *** Thirty-two unique studies were included for the final *** involved were divided into two groups：Group 1（G1） and Group 2（G2） comprising of Asian and Caucasian populations,*** thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio（OR）：3.62,95% confidence interval（CI）：2.83-4.65] and G2（OR：1.35,95% CI：1.17-1.56）;hypothyroidism,only in G2（OR：1.20,CI：1.09-1.33）;and subclinical hypothyroidism or hypothyroxinemia,in neither *** Thyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities,compared with thyroid dysfunction.

关键词： Thyroid Hypothyroidism Autoimmunity Preterm birth Ethnicity

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population

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World Journal of Gastroenterology 2017年第32期23卷 5945-5953页

作者： Jin-Hua Shan Xiao-Juan Bai Lu-Lu Han Yuan Yuan Xue-Feng Sun Department of gerontology and geriatrics the First Affiliated Hospital of China Medical University Department of gerontology and geriatrics Shengjing Hospital of China Medical University Department of Tumor Research the First Affiliated Hospital of China Medical University Department of Kidney General Hospital of Chinese People’s Liberation Army

AIM To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori(H. pylori) infection in a healthy population, and explore factors associated with gastric *** Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen(PG)Ⅰ and Ⅱ, gastrin-17(G-17) and H. pylori antibody levels. Analyses were made by Student's t-test, ANOVA, Pearson's correlation and multiple linear *** PGII levels were higher in the ≥ 65-years-old age group(P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group(P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol(LDL-C) were higher(P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group(P < 0.05) for H. pylori-infected subjects and 45-64-yearsold age group(P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-Ig G level positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII(P < 0.001). Creatinine positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose(FBG) positively correlated with PGⅠ/PGⅡ and G-17(P < 0.001, P = 0.037). Age positively correlated with PGII and G-17(P = 0.005, P = 0.026).CONCLUSION PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

关键词： Helicobacter pylori antibody Pepsinogen Gastrin Gastric ageing

Association between ventricular repolarization variables and cardiac diastolic function: A cross-sectional study of a healthy Chinese population

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World Journal of Clinical Cases 2019年第8期7卷 940-950页

作者： Zhi-Dan Li Xiao-Juan Bai Lu-Lu Han Wen Han Xue-Feng Sun Xiang-Mei Chen Department of gerontology and geriatrics Shengjing Hospital of China Medical University Department of Kidney General Hospital of Chinese People's Liberation Army

BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval,Tpeak-to-Tend(Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese *** To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese *** This was a community-based cross-sectional study conducted in Shenyang,China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography(ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity(E) and late diastolic inflow velocity(A), E-wave deceleration time, left atrial volume(LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine *** Ventricular repolarization variables, such as the QTc interval(393.59 ± 26.74 vs403.86 ± 33.56; P < 0.001), Tpe interval(72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01),Tpec interval(76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio(0.19 ±0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic *** adjusting for all other possible confounders, the QTc and Tpe_c intervals were significantly associated with the E/A ratio(P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastoli

关键词： QT interval Tpeak-to-Tend interval Diastolic dysfunction Ventricular repolarization Electrocardiography

Frailty Prevalence and Characteristics in Older Patients with Type 2 Diabetes

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Journal of Diabetes Mellitus 2019年第2期9卷 31-38页

作者： Takahisa Tanikawa Sayuri Sable-Morita Haruhiko Tokuda Hidenori Arai Department of Endocrinology National Center for Geriatrics and Gerontology Obu Japan Nursing Department National Center for Geriatrics and Gerontology Obu Japan Department of Clinical Laboratory National Center for Geriatrics and Gerontology Obu Japan National Center for geriatrics and gerontology Obu Japan

Background: Older diabetic patients are more likely to be frail than those who do not have diabetes. Frailty is an important risk factor for both mortality and disability in older patients with type 2 diabetes. However, the mechanism of frailty in diabetes mellitus is not fully understood. Aims: The aim of this study was to identify the prevalence of frailty and associated factors in older patients with type 2 diabetes in Japan. Methods: A cross-sectional study was conducted with a total of 178 outpatients who were over 65 years old with type 2 diabetes. We used the Obu Study Health Promotion for the Elderly definition of frailty to divided subjects into a non-frail and a frail group. We investigated the association between frailty and various patient characteristics. Results: In the study, 21.4% of the older patients with type 2 diabetes were considered frail. There were no significant differences in the duration of diabetes, BMI, proportion of microvascular complications, or HbA1c values between the frail and non-frail group. However, serum albumin and IGF-1 levels were lower in the frail group than the non-frail group as were the Mini-Mental State Examination scores. The frail group had a higher number of medications than the non-frail group. In a multivariable analysis, frailty was positively associated with the number of medications and, lower levels of both serum albumin and IGF-1. Conclusion: Our study suggests that diabetes accelerates the aging process and frailty is associated with low albumin, polypharmacy and low levels of IGF-1.

关键词： Frailty Albumin Insulin-Like Growth Factor-1 Polypharmacy

Coronary revascularization in the elderly with stable angina

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Journal of Geriatric Cardiology 2015年第5期12卷 555-568页

作者： Kirill Lenarovich Kozlov Aleksandr Andreevich Bogachev Laboratory of Age-Related Clinical Pathology Department of Clinical Gerontology and Geriatrics St. Petersburg Institute of Bioregulation and Gerontology Northwestern Branch Russian Academy of Medical Sciences Saint-Petersburg Russia Department of Cardiovascular Medicine Kirov Military Medical Academy Saint-Petersburg Russia

A proportion of elderly with coronary artery disease is rapidly growing. They have more severe coronary artery disease, therefore, derive more benefit fi＇om revascularization and have a greater need for it. The elderly is a heterogeneous group, but compared to the younger cohort, the choice of the optimal revascularization method is much more complicated among them. In recent decades, results has improved dramatically both in surgery and percutaneous coronary intervention （PCI）, even in very old persons. Despite the lack of evidence in elderly, it is obvious, that coronary artery bypass surgery （CABG） has a more pronounced effect on long-term survival in price of more strokes, while PCI is certainly less invasive. Age itself is not a criterion for the selection of treatment strategy, but the elderly are often more interested in quality of life and personal independence instead of longevity. This article discusses the factors that influence the choice of the revascularization method in the elderly with stable angina and presents a complex algorithm for making an individual risk-benefit profile. As a consequence the features of CABG and PCI in elderly patients are exposed. Emphasis is centered on the frailty and non-medical factors, including psychosocial, as essential components in making the decision of what strategy to choose. Good communication with the patients and giving them unbiased information is encouraged.

关键词： Angina Cardiopulmonary bypass Coronary artery disease Stents The elderly

Involvement of insulin receptor substrates in cognitive impairment and Alzheimer’s disease

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Neural Regeneration Research 2019年第8期14卷 1330-1334页

作者： Daisuke Tanokashira Wataru Fukuokaya Akiko Taguchi Department of Integrative Aging Neuroscience National Center for Geriatrics and Gerontology Obu Aichi Japan Division of Neurology Endocrinology and Metabolism Faculty of Medicine University of Miyazaki Miyazaki Japan

Type 2 diabetes一associated with impaired insulin/insulin-like growth factor-1 (IGF1) signaling (IIS)一is a risk factor for cognitive impairment and dementia including Alzheimer's disease (AD). The insulin receptor substrate (IRS) proteins are major components of IIS, which transmit upstream signals via the insulin receptor and/or IGF1 receptor to multiple intracellular signaling pathways, including AKT/protein kinase B and extracellular-signal-regulated kinase cascades. Of the four IRS proteins in mammals, IRS1 and IRS2 play key roles in regulating growth and survival, metabolism, and aging. Meanwhile, the roles of IRS1 and IRS2 in the central nervous system with respect to cognitive abilities remain to be clarified. In contrast to IRS2 in peripheral tissues, inactivation of neural IRS2 exerts beneficial effects, resulting in the reduction of amyloid p accumulation and premature mortality in AD mouse models. On the other hand, the increased phosphorylation of IRS 1 at several serine sites is observed in the brains from patients with AD and animal models of AD or cognitive impairment induced by type 2 diabetes. However, these serine sites are also activated in a mouse model of type 2 diabetes, in which the diabetes drug metformin improves memory impairment. Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown. Here, we examine the associations between IRS 1 /1 RS2-mediated signaling in the central nervous system and cognitive decline.

关键词： type 2 diabetes insulin/insulin^like growth factor-1 insulin receptor substrate Alzheimer's disease aging serine phosphorylation metformin neuroprotective effects high-fat-diet

Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies

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Biomedical and Environmental Sciences 2024年第5期37卷 503-510页

作者： LI Min ZHANG Yu Lan ZHANG Kai Li LI Ping Ping LYU Yu Han LIANG Ya Xin YU Yue Department of Gynecology and Obstetrics Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing HospitalBeijing 100730China The Key Laboratory of geriatrics Beijing Institute of GeriatricsBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective VATER/VACTERL-like association is associated with adverse pregnancy *** evidence of this disorder is *** this study,we aimed to provide genetic insights to improve the diagnosis of *** We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like *** and genetic analyses were conducted using genome and exome *** Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome *** sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 *** family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in *** These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like ***,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

关键词： Prenatal diagnosis VACTERL whole-genome sequencing whole-exome sequencing X-linked

CLINICAL FEATURES OF MULTIPLE ORGAN FAILURE IN THE ELDERLY

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中华医学杂志(英文版) 1990年第9期103卷 763-767页

作者：王士雯范利 Institute of gerontology and geriatrics the Chinese PLA General Hospital Beijing 100853

Multiple organ failure (MOF) in the elderly is a new syndrome evolved from multiple organ chronic diseases on the basis of multiple organ dysfunction in the aged. Its characteristics are clinically different from those of MOF due to serious trauma. 122 cases of MOF were analysed retrospectively and their clinical features discussed. MOF with a long course is the natural presentation in many of the elderly before death. Its main precipitating factors are pulmonary infection, metastatic carcinoma, cardiac attack, etc. The sequence of a failure in organs is heart, lung, kidney,liver, etc. The mortality is similar to that of MOF due to trauma. However, those suffering from 4-organ failure can still survive, and instead, the renal failure can be mostly fatal. More attention should be paid to the prevention of MOF in the elderly so as to shorten its developing course.

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