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Cover Illustration
2019, Vol.10  No.1
Figure 2. Phenotype characterization of LMNA-KO rabbits. Behavioral photographs cut from video of the LMNA-KO-1, LMNA-KO-2, and WT control.

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  • Table of Content
      01 February 2019, Volume 10 Issue 1 Previous Issue   
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    Orginal Article
    Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study
    Jong Bin Bae,Ji Won Han,Kyung Phil Kwak,Bong Jo Kim,Shin Gyeom Kim,Jeong Lan Kim,Tae Hui Kim,Seung-Ho Ryu,Seok Woo Moon,Joon Hyuk Park,Jong Chul Youn,Dong Young Lee,Dong Woo Lee,Seok Bum Lee,Jung Jae Lee,Jin Hyeong Jhoo,Ki Woong Kim
    Aging and disease. 2019, 10 (1): 1-11.   DOI: 10.14336/AD.2018.0123
    Abstract   HTML   PDF (649KB) ( 814 )

    Dementia increases the risk of mortality (ROM) in the elderly and estimates of hazard ratio (HR) of dementia for mortality have ranged from 1.7 to 6.3. However, previous studies may have underestimated ROM of dementia due to length bias, which occurs when failing to include the persons with rapidly progressive diseases, who died before they could be included in the study. This population-based prospective cohort study conducted on 6,752 randomly sampled Koreans, aged 60 years or older (the Korean Longitudinal Study on Cognitive Aging and Dementia). Cognitive disorders were evaluated at baseline and 2-year follow-up using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K), and prevalent and incident cases of dementia were identified. The participants’ deaths were confirmed through the National Mortality Database of Statistics Korea. We compared the ROM between prevalent and incident dementia, and estimated HR of dementia for mortality using Cox proportional hazards model. Of the 5,097 responders to the 2-year follow-up assessment, 150 participants had dementia from the baseline (prevalent dementia), and 95 participants developed dementia during the 2-year follow-up period (incident dementia). The ROM of participants with incident dementia was about 3 times higher than the ROM of those with prevalent dementia (HR = 3.04, 95% confidence interval [CI] = 1.34-6.91). Compared to cognitively normal participants at both the baseline and 2-year follow-up assessments, the ROM of those with incident dementia approximately 8 times higher (HR = 8.37, 95 % CI = 4.23-16.54). In conclusion, the ROM of dementia using prevalent cases was underestimated due to length bias, and dementia may be much more fatal than previously estimated. In clinical settings, the ROM of dementia warrants the attention of physicians, particularly in recently incident dementia cases.

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    Quantitative Evaluation of Gait Disturbance on an Instrumented Timed Up-and-go Test
    Shigeki Yamada,Yukihiko Aoyagi,Kazuo Yamamoto,Masatsune Ishikawa
    Aging and disease. 2019, 10 (1): 23-36.   DOI: 10.14336/AD.2018.0426
    Abstract   HTML   PDF (1589KB) ( 993 )

    Although the 3-m timed up-and-go test (TUG) is reliable for evaluating mobility, TUG time is insufficient to evaluate mild gait disturbance; we, therefore aimed to investigate other measurements with instrumented TUG (iTUG) using a free smartphone application. Our inclusion criterion in this study is only that participants can walk without any assistance. This study included three heterogeneous groups; patients who underwent a tap test or shunt surgery, 29 inpatients hospitalized for other reasons, and 87 day-care users. After the tap test, 28 were diagnosed with tap-positive idiopathic normal-pressure hydrocephalus (iNPH) and 8 were diagnosed with tap-negative. Additionally, 18 patients were assessed iTUG before and after shunt surgery. During iTUG, time and 3-dimensional (3D) acceleration were automatically recorded every 0.01 s. A volume of the 95% confidence ellipsoid (95%CE) of all plots for 3D acceleration was calculated. Additionally, an iTUG score was defined as (95%CE volume) 0.8 / 1.9 - 1.9 × (time) + 60. The measurement reliability was evaluated using intraclass correlations and Bland-Altman plots. The participants with mild gait disturbance who accomplished within 13.5 s on the iTUG time had the 95%CE volumes for 3D acceleration of ≥70 m3/s6 and iTUG scores of ≥50. The mean iTUG time was shortened and the mean 95%CE volumes and iTUG scores were increased after the tap test among 28 patients with tap-positive iNPH and after shunt surgery among 18 patients with definite iNPH. Conversely, the mean iTUG score among 8 patients with tap-negative was decreased after the tap test. The intraclass correlations for the time, 95%CE volume and iTUG score were 0.97, 0.80 and 0.90, respectively. Not only the iTUG time but also the 95%CE volume was important for evaluating mobility. Therefore, the novel iTUG score consisting both is useful for the quantitative assessment of mobility.

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    Metformin and the Risk of Dementia in Type 2 Diabetes Patients
    Tseng Chin-Hsiao
    Aging and disease. 2019, 10 (1): 37-48.   DOI: 10.14336/AD.2017.1202
    Abstract   HTML   PDF (607KB) ( 854 )

    This retrospective cohort study investigated dementia risk associated with metformin use in type 2 diabetes patients by using the reimbursement database of the Taiwan’s National Health Insurance. The patients had new-onset diabetes during 1999-2005 and were followed up until December 31, 2011. An unmatched cohort of 147,729 ever users and 15,676 never users of metformin were identified, and a matched-pair cohort of 15,676 ever users and 15,676 never users was created by propensity score (PS). Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Results showed that in the unmatched cohort, 713 never users and 3943 ever users developed dementia with respective incidence of 1029.20 and 570.03 per 100,000 person-years. The overall hazard ratio was 0.550 (95% confidence interval: 0.508-0.596). The hazard ratio for the first (<27.0 months), second (27.0-58.1 months) and third (>58.1 months) tertile of cumulative duration of metformin therapy was 0.975 (0.893-1.066), 0.554 (0.506-0.607) and 0.286 (0.259-0.315), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.707 (0.632-0.791) and the hazard ratio for the respective tertile was 1.279 (1.100-1.488), 0.704 (0.598-0.829) and 0.387 (0.320-0.468). In conclusion, metformin use is associated with a reduced dementia risk.

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    Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population
    Geraldo Rubens Ramos Freitas,Maria da Luz Fernandes,Fabiana Agena,Omar Jaluul,Sérgio Colenci Silva,Francine Brambate Carvalhinho Lemos,Verônica Coelho,David-Neto Elias,Nelson Zocoler Galante
    Aging and disease. 2019, 10 (1): 49-61.   DOI: 10.14336/AD.2018.0318
    Abstract   HTML   PDF (883KB) ( 711 )

    There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26±2y), healthy elderly (HEld) (n=15, 79±7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36±7y) and ESRD elderly (EnEld) (n=31, 65±3y) prior to Ktx regarding their naïve, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4+ memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required. (ClinicalTrials.gov number: NTC01631058).

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    Distribution Pattern of Atherosclerotic Stenosis in Chinese Patients with Stroke: A Multicenter Registry Study
    Yang Hua,Lingyun Jia,Yingqi Xing,Pinjing Hui,Xuan Meng,Delin Yu,Xiaofang Pan,Yalan Fang,Binbin Song,Chunxia Wu,Chunmei Zhang,Xiufang Sui,Youhe Jin,Jingfen Zhang,Jianwei Li,Ling Wang,Yuming Mu,Jingxin Zhong,Yuhong Zhu,Heng Zhang,Xiaoyu Cai
    Aging and disease. 2019, 10 (1): 62-70.   DOI: 10.14336/AD.2018.0602
    Abstract   HTML   PDF (471KB) ( 598 )

    The aim of this multicenter study was to demonstrate the distribution pattern of atherosclerotic stenosis and its trend with aging between extracranial and intracranial arteries and its distribution between the anterior and posterior circulations in Chinese patients hospitalized with ischemic stroke. In addition, the risk factors for the distribution pattern were illustrated. From June 2015 to May 2016, 9,346 patients with ischemic stroke from 20 hospitals were enrolled. Carotid artery ultrasonography and transcranial color-coded sonography/transcranial Doppler were used to evaluate the extracranial and intracranial arteries. The distribution pattern of atherosclerotic stenosis and its trend with aging were analyzed. Logistic regression was used to analyze the risk factors for the distribution pattern. Among the 9,346 patients, 2,882 patients (30.8%) had at least one artery with a degree of stenosis ≥50%. Among patients with arterial stenosis, the proportion of patients with intracranial artery stenosis was higher than those with extracranial artery stenosis (52.6% vs. 27.6%), and the proportion of anterior circulation artery stenosis was higher than that in the posterior circulation (52.2% vs.26.2%). With aging, the proportion of intracranial artery stenosis alone decreased; at the same time, the proportion of extracranial artery stenosis and extracranial plus intracranial artery stenosis increased (trend χ2=6.698, P=0.001). Hypertension (OR 1.416, P=0.008) and family history of stroke (OR 1.479, P=0.014) were risk factors for intracranial artery stenosis. Male, aging, and smoking were factors more related to extracranial artery stenosis. Aging (OR 1.022, P<0.001) and hypertension (OR 1.392, P=0.019) were related to posterior circulation artery stenosis. Intracranial arteries and anterior circulation arteries were susceptible to stenosis in Chinese patients with ischemic stroke. However, the distribution pattern of atherosclerotic stenosis was dynamic and varied with aging. Aging and different risk factors contribute to this distribution pattern.

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    Chronic Kidney Disease Is Linked to Carotid Nodular Calcification, An Unstable Plaque Not Correlated to Inflammation
    Marina Cardellini,Valentina Rovella,Manuel Scimeca,Lucia Anemona,Simone Bischetti,Sara Casella,Andrea Saggini,Elena Bonanno,Marta Ballanti,Francesca Davato,Rossella Menghini,Arnaldo Ippoliti,Giuseppe Santeusanio,Nicola Di Daniele,Massimo Federici,Alessandro Mauriello
    Aging and disease. 2019, 10 (1): 71-81.   DOI: 10.14336/AD.2018.0117
    Abstract   HTML   PDF (584KB) ( 511 )

    The incidence and the different type of carotid calcifications, nodular and non-nodular, and their role in the acute cerebrovascular disease has not yet been defined. Various studies have correlated the presence of specific risk factors, in particular the chronic kidney disease, with the presence of calcification, but not with the type of calcification. Since it is likely that carotid nodular calcifications rather than those with non-nodular aspect may represent a plaque at high risk of rupture, the purpose of our study was to evaluate the role of nodular calcification in the pathogenesis of cerebrovascular syndromes and their possible correlation with specific risk factors. A total of 168 carotid plaques from symptomatic and asymptomatic patients submitted to endarterectomy, whom complete clinical and laboratory assessment of major cardiovascular risk factors was available, were studied. In 21 endarterectomies (5 from symptomatic and 16 from asymptomatic patients) an eruptive calcified nodule, consisting of calcified plates associated to a small amount of fibrous tissue without extracellular lipids and inflammatory cells, was found protruding into the lumen. Nodular calcifications were significantly observed in patients affected by chronic kidney disease (with GFR<60 ml / min / 1.73 m2), with a normal lipidic and glycemic profile. On the contrary, non-nodular calcification, mainly correlated to diabetes, were stable lesions. Results of our study suggest that the mechanisms and the clinical significance of carotid atherosclerotic calcification may be different. The nodular calcification could represent a type of unstable plaque, significantly related to chronic kidney disease, without inflammation, morphologically different from the classical vulnerable plaques.

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    DRAM is Involved in Hypoxia/Ischemia-Induced Autophagic Apoptosis in Hepatocytes
    Jianji Xu,Yunjin Zang,Dongjie Liu,Tongwang Yang,Jieling Wang,Yanjun Wang,Xiaoni Liu,Dexi Chen
    Aging and disease. 2019, 10 (1): 82-93.   DOI: 10.14336/AD.2018.0210
    Abstract   HTML   PDF (2577KB) ( 679 )

    Liver hypoxia/ischemia injury leads to acute liver injury, delayed graft dysfunction, and failure during liver transplantation. Previous studies showed that autophagy is involved in liver hypoxia/ischemia injury. Our and others’ studies have found that the damage-regulated autophagy modulator (DRAM) could induce the autophagic apoptosis. However, the role of DRAM regulating autophagy in liver hypoxia/ischemia injury remains unclear. The aim of this study was to determine whether DRAM is involved in oxygen-glucose deprivation (OGD)-induced hepatocyte autophagic apoptosis. Normal hepatocytes (HL-7702) were treated with OGD while Balb/c mice underwent surgery to induce 70% liver ischemia. To evaluate the role of DRAM in hypoxia/ischemia-induced hepatic injury, DRAM siRNA was used to knockdown DRAM expression in cultured hepatocytes and a recombinant adenovirus vector expressing DRAM was used to overexpress DRAM in cultured hepatocytes in vitro and in the liver in vivo. Hepatic injury was analyzed by histopathological methods and measurement of hepatocyte enzyme release. Cell apoptosis was analyzed by flow cytometry and TUNEL staining. Several autophagic biomarkers were observed by western blot analysis. OGD and 70% hepatic ischemia significantly induced cell autophagy, apoptosis and DRAM expression in hepatocytes in vitro and in vivo. OGD-induced autophagic apoptosis was inhibited by 3-Methyladenine (3-MA). OGD-induced injury and autophagy in HL-7702 cells were significantly attenuated by DRAM knockdown but aggravated by DRAM overexpression in vitro. Similarly, DRAM overexpression increased ischemia-induced liver injury and hepatic apoptosis in vivo. Our data demonstrate that hypoxia/ischemia induces hepatic injury through a DRAM-dependent autophagic apoptosis pathway. These data also suggest that DRAM plays an important role in ischemia-induced liver injury and hepatocyte apoptosis.

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    REST rs3796529 Genotype and Rate of Functional Deterioration in Alzheimer’s Disease
    Poyin Huang,Cheng-Sheng Chen,Yuan-Han Yang,Mei-Chuan Chou,Ya-Hsuan Chang,Chiou-Lian Lai,Hsuan-Yu Chen,Ching-Kuan Liu
    Aging and disease. 2019, 10 (1): 94-101.   DOI: 10.14336/AD.2018.0116
    Abstract   HTML   PDF (537KB) ( 1241 )

    Recently, REST (RE1-silencing transcription factor) gene has been shown to be lost in Alzheimer’s disease (AD), and a missense minor REST allele rs3796529-T has been shown to reduce the rate of hippocampal volume loss. However, whether the REST rs3796529 genotype is associated with the rate of functional deterioration in AD is unknown. A total of 584 blood samples from Taiwanese patients with AD were collected from January 2002 to December 2013. The diagnosis of AD was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria. The allele frequency of rs3796529-T was compared between the AD cohort and 993 individuals from the general population in Taiwan. Kaplan-Meier analysis, the log rank test and a multivariate Cox model were then used to evaluate the association between rs3796529-T and functional deterioration in the AD cohort. The allele frequency of rs3796529-T was significantly lower in the AD cohort compared to the general population cohort (36.82% vs. 40.73%, p=0.029). Kaplan-Meier analysis and the log rank test showed that the AD patients carrying the rs3796529 T/T genotype had a longer progression-free survival than those with the C/C genotype (p=0.012). In multivariate analysis, the rs3796529 T/T genotype (adjusted HR=0.593, 95% CI: 0.401-0.877, p=0.009) was an independent protective factor for functional deterioration. The rs3796529 T/T genotype was associated with slower functional deterioration in patients with AD. This finding may lead to a to better understanding of the molecular pathways involved, and prompt further development of novel biomarkers to monitor AD.

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    LMNA-mutated Rabbits: A Model of Premature Aging Syndrome with Muscular Dystrophy and Dilated Cardiomyopathy
    Tingting Sui,Di Liu,Tingjun Liu,Jichao Deng,Mao Chen,Yuanyuan Xu,Yuning Song,Hongsheng Ouyang,Liangxue Lai,Zhanjun Li
    Aging and disease. 2019, 10 (1): 102-115.   DOI: 10.14336/AD.2018.0209
    Abstract   HTML   PDF (1942KB) ( 802 )

    Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. Products of the LMNA gene, primarily lamin A and C, are major components of the nuclear lamina. A recently identified group of premature aging syndromes was related to mutations of the LMNA gene. Although LMNA disorders have been identified in premature aging syndromes, affect specifically the skeletal muscles, cardiac muscles, and lipodystrophy, understanding the pathogenic mechanisms still need to be elucidated. Here, to establish a rabbit knockout (KO) model of premature aging syndromes, we performed precise LMNA targeting in rabbits via co-injection of Cas9/sgRNA mRNA into zygotes. The LMNA-KO rabbits exhibited reduced locomotion activity with abnormal stiff walking posture and a shortened stature, all of them died within 22 days. In addition, cardiomyopathy, muscular dystrophy, bone and joint abnormalities, as well as lipodystrophy were observed in LMNA-KO rabbits. In conclusion, the novel rabbit LMNA-KO model, displayed typical features of histopathological defects that are observed in premature aging syndromes, and may be utilized as a valuable resource for understanding the pathophysiological mechanisms of premature aging syndromes and elucidating mysteries of the normal process of aging in humans.

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    Snapshot: Implications for mTOR in Aging-related Ischemia/Reperfusion Injury
    Dong Liu,Liqun Xu,Xiaoyan Zhang,Changhong Shi,Shubin Qiao,Zhiqiang Ma,Jiansong Yuan
    Aging and disease. 2019, 10 (1): 116-133.   DOI: 10.14336/AD.2018.0501
    Abstract   HTML   PDF (980KB) ( 959 )

    Aging may aggravate the damage and dysfunction of different components of multiorgan and thus increasing multiorgan ischemia/reperfusion (IR) injury. IR injury occurs in many organs and tissues, which is a major cause of morbidity and mortality worldwide. The kinase mammalian target of rapamycin (mTOR), an atypical serine/threonine protein kinase, involves in the pathophysiological process of IR injury. In this review, we first briefly introduce the molecular features of mTOR, the association between mTOR and aging, and especially its role on autophagy. Special focus is placed on the roles of mTOR during ischemic and IR injury. We then clarify the association between mTOR and conditioning phenomena. Following this background, we expand our discussion to potential future directions of research in this area. Collectively, information reviewed herein will serve as a comprehensive reference for the actions of mTOR in IR injury and may be significant for the design of future research and increase the potential of mTOR as a therapeutic target.

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    Rosenroot (Rhodiola): Potential Applications in Aging-related Diseases
    Wei Zhuang,Lifeng Yue,Xiaofang Dang,Fei Chen,Yuewen Gong,Xiaolan Lin,Yumin Luo
    Aging and disease. 2019, 10 (1): 134-146.   DOI: 10.14336/AD.2018.0511
    Abstract   HTML   PDF (476KB) ( 886 )

    Aging is a progressive accumulation of changes in the body, which increases the susceptibility to diseases such as Alzheimer’s disease, Parkinson’s disease, cerebrovascular disease, diabetes, and cardiovascular disease. Recently, Chinese medicinal herbs have been investigated for their therapeutic efficacy in the treatment of some aging-related diseases. Rhodiola, known as ‘Hongjingtian’ in Chinese, has been reported to have anti-aging activity. Here, we provide a comprehensive review about its origin, chemical constituents, and effects on aging-related diseases.

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    Elevated Inflammatory Status and Increased Risk of Chronic Disease in Chronological Aging: Inflamm-aging or Inflamm-inactivity?
    Michael G. Flynn,Melissa M. Markofski,Andres E. Carrillo
    Aging and disease. 2019, 10 (1): 147-156.   DOI: 10.14336/AD.2018.0326
    Abstract   HTML   PDF (394KB) ( 812 )

    Age-associated hyper-inflammation or “inflamm-aging” has been linked to the development of chronic diseases and characterized as an unavoidable aspect of aging. However, the inflamm-aging model does not adequately address the potential anti-inflammatory effects of exercise training and the potential for exercise to ameliorate several age-related diseases. In this brief review, we introduce a new paradigm—inflamm-inactivity—that describes a potent counter-measure to age-associated inflammatory illness.

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    Prospective Views for Whey Protein and/or Resistance Training Against Age-related Sarcopenia
    Yuxiao Liao,Zhao Peng,Liangkai Chen,Yan Zhang,Qian Cheng,Andreas K. Nüssler,Wei Bao,Liegang Liu,Wei Yang
    Aging and disease. 2019, 10 (1): 157-173.   DOI: 10.14336/AD.2018.0325
    Abstract   HTML   PDF (776KB) ( 1369 )

    Skeletal muscle aging is characterized by decline in skeletal muscle mass and function along with growing age, which consequently leads to age-related sarcopenia, if without any preventive timely treatment. Moreover, age-related sarcopenia in elder people would contribute to falls and fractures, disability, poor quality of life, increased use of hospital services and even mortality. Whey protein (WP) and/or resistance training (RT) has shown promise in preventing and treating age-related sarcopenia. It seems that sex hormones could be potential contributors for gender differences in skeletal muscle and age-related sarcopenia. In addition, skeletal muscle and the development of sarcopenia are influenced by gut microbiota, which in turn is affected by WP or RT. Gut microbiota may be a key factor for WP and/or RT against age-related sarcopenia. Therefore, focusing on sex hormones and gut microbiota may do great help for preventing, treating and better understanding age-related sarcopenia.

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    Epigenetic Regulation of Bone Marrow Stem Cell Aging: Revealing Epigenetic Signatures associated with Hematopoietic and Mesenchymal Stem Cell Aging
    Dimitrios Cakouros,Stan Gronthos
    Aging and disease. 2019, 10 (1): 174-189.   DOI: 10.14336/AD.2017.1213
    Abstract   HTML   PDF (708KB) ( 1380 )

    In this review we explore the importance of epigenetics as a contributing factor for aging adult stem cells. We summarize the latest findings of epigenetic factors deregulated as adult stem cells age and the consequence on stem cell self-renewal and differentiation, with a focus on adult stem cells in the bone marrow. With the latest whole genome bisulphite sequencing and chromatin immunoprecipitations we are able to decipher an emerging pattern common for adult stem cells in the bone marrow niche and how this might correlate to epigenetic enzymes deregulated during aging. We begin by briefly discussing the initial observations in yeast, drosophila and Caenorhabditis elegans (C. elegans) that led to the breakthrough research that identified the role of epigenetic changes associated with lifespan and aging. We then focus on adult stem cells, specifically in the bone marrow, which lends strong support for the deregulation of DNA methyltransferases, histone deacetylases, acetylates, methyltransferases and demethylases in aging stem cells, and how their corresponding epigenetic modifications influence gene expression and the aging phenotype. Given the reversible nature of epigenetic modifications we envisage “epi” targeted therapy as a means to reprogram aged stem cells into their younger counterparts.

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    Relationship between Hypothyroidism and Endometrial Cancer
    Yiqin Wang,Rong Zhou,Jianliu Wang
    Aging and disease. 2019, 10 (1): 190-196.   DOI: 10.14336/AD.2018.0224
    Abstract   HTML   PDF (317KB) ( 1384 )

    Thyroid dysfunction is involved in several types of carcinoma. Hypothyroidism is one of the most common medical morbidities among patients with endometrial cancer; however, the related mechanism is unclear. Among the risk factors related to endometrial cancer, hypothyroidism interacts with metabolic syndrome, polycystic ovarian syndrome and infertility or directly acts on the endometrium itself, which may influence the development and progression of endometrial cancer. We summarize recent studies on the relationship between hypothyroidism and endometrial cancer and its risk factors to provide references for basic research as well as for clinical treatment and prognostic evaluation.

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    Short Communications
    Reduction in IGF1 mRNA in the Human Subependymal Zone During Aging
    Christin Weissleder,Guy Barry,Samantha J. Fung,Matthew W. Wong,Kay L. Double,Maree J. Webster,Cynthia Shannon Weickert
    Aging and disease. 2019, 10 (1): 197-204.   DOI: 10.14336/AD.2018.0317
    Abstract   HTML   PDF (453KB) ( 567 )

    The cell proliferation marker, Ki67 and the immature neuron marker, doublecortin are both expressed in the major human neurogenic niche, the subependymal zone (SEZ), but expression progressively decreases across the adult lifespan (PMID: 27932973). In contrast, transcript levels of several mitogens (transforming growth factor α, epidermal growth factor and fibroblast growth factor 2) do not decline with age in the human SEZ, suggesting that other growth factors may contribute to the reduced neurogenic potential. While insulin like growth factor 1 (IGF1) regulates neurogenesis throughout aging in the mouse brain, the extent to which IGF1 and IGF family members change with age and relate to adult neurogenesis markers in the human SEZ has not yet been determined. We used quantitative polymerase chain reaction to examine gene expression of seven IGF family members [IGF1, IGF1 receptor, insulin receptor and high-affinity IGF binding proteins (IGFBPs) 2, 3, 4 and 5] in the human SEZ across the adult lifespan (n=50, 21-103 years). We found that only IGF1 expression significantly decreased with increasing age. IGFBP2 and IGFBP4 expression positively correlated with Ki67 mRNA. IGF1 expression positively correlated with doublecortin mRNA, whereas IGFBP2 expression negatively correlated with doublecortin mRNA. Our results suggest IGF family members are local regulators of neurogenesis and indicate that the age-related reduction in IGF1 mRNA may limit new neuron production by restricting neuronal differentiation in the human SEZ.

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Kunlin Jin, M.D., Ph.D., Professor
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David A. Greenberg, M.D., Ph.D., Professor
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