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2016, Vol.7  No.1
MHC immunofluorescence labeling was apparent in transverse sections of contralateral and exposed TA muscles following chronic SSC exposure. MHC immunofluorescence labeling was appare [Detail] ...

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  • Table of Content
      01 February 2016, Volume 7 Issue 1 Previous Issue    Next Issue
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    Original Article
    Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats
    P. Rader Erik, N. Layner Kayla, M. Triscuit Alyssa, D. Chetlin Robert, Ensey James, A. Baker Brent
    Aging and disease. 2016, 7 (1): 1-13.   DOI: 10.14336/AD.2015.0920
    Abstract   HTML   PDF (1388KB) ( 1199 )

    Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

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    Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity
    Hu Heng, N. Doll Danielle, Sun Jiahong, E. Lewis Sara, H. Wimsatt Jeffrey, J. Kessler Matthew, W. Simpkins James, Ren Xuefang
    Aging and disease. 2016, 7 (1): 14-27.   DOI: 10.14336/AD.2015.0906
    Abstract   HTML   PDF (2130KB) ( 1622 )

    Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy.

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    Evaluation of Cardiac Autonomic Functions in Older Parkinson’s Disease Patients: a Cross-Sectional Study
    Yalcin Ahmet, Atmis Volkan, Karaarslan Cengiz Ozlem, Cinar Esat, Aras Sevgi, Varli Murat, Atli Teslime
    Aging and disease. 2016, 7 (1): 28-35.   DOI: 10.14336/AD.2015.0819
    Abstract   HTML   PDF (0KB) ( 2511 )

    In Parkinson’s disease (PD), non-motor symptoms may occur such as autonomic dysfunction. We aimed to evaluate both parasympathetic and sympathetic cardiovascular autonomic dysfunction in older PD cases. 84 PD cases and 58 controls, for a total of 142, participated in the study. Parasympathetic tests were performed using electrocardiography. Sympathetic tests were assessed by blood pressure measurement and 24-hour ambulatory blood pressure measurement. The prevalence of orthostatic hypotension in PD patients was 40.5% in PD patients and 24.1% in the control group (p> 0.05). The prevalence of postprandial hypotension was 47.9% in the PD group and 27.5% in the controls (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 26.2% in the PD group and 6.9% in the control group (p <0.05). The prevalence of postprandial hypotension in PD with orthostatic hypotension was 94% and 16% in PD patients without orthostatic hypotension (p <0.05). The prevalence of impairment in heart rate response to deep breathing was 52.9% in PD patients with orthostatic hypotension and 8% in PD cases without orthostatic hypotension (p<0.05). The prevalence of impairment in heart rate response to postural change was 41% in PD cases with orthostatic hypotension and 12% in PD cases without orthostatic hypotension (p <0.05).Although there are tests for assessing cardiovascular autonomic function that are more reliable, they are more complicated, and evaluation of orthostatic hypotension by blood pressure measurement and cardiac autonomic tests by electrocardiography are recommended since these tests are cheap and easy.

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    Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis
    Zhang Jing-Zhan, Xie Xiang, Ma Yi-Tong, Zheng Ying-Ying, Yang Yi-Ning, Li Xiao-Mei, Fu Zhen-Yan, Dai Chuan-Fang, Zhang Ming-Ming, Yin Guo-Ting, Liu Fen, Chen Bang-Dang, Gai Min-Tao
    Aging and disease. 2016, 7 (1): 36-44.   DOI: 10.14336/AD.2015.0709
    Abstract   HTML   PDF (503KB) ( 1426 )

    Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility.

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    Quality of Life Impact Related to Foot Health in a Sample of Older People with Hallux Valgus
    López López Daniel, Callejo González Lucía, Elena Losa Iglesias Marta, Luis Saleta Canosa Jesús, Rodríguez Sanz David, Calvo Lobo Cesar, Becerro de Bengoa Vallejo Ricardo
    Aging and disease. 2016, 7 (1): 45-52.   DOI: 10.14336/AD.2015.0914
    Abstract   HTML   PDF (653KB) ( 1686 )

    Hallux Valgus (HV) is a highly prevalent forefoot deformity in older people associated with progressive subluxation and osteoarthritis of the first metatarsophalangeal (MTP) joint and it is believed to be associated with varying degrees of HV effect on the quality of life related to foot health.The aim of this study is to compare the impact of varying degrees of HV on foot health in a sample of older people. The sample consisted of 115 participants, mean age 76.7 ± 9.1, who attended an outpatient center where self-report data were recorded. The degree of HV deformity was determined in both feet using the Manchester Scale (MS) from stage 1 (mild) to 4 (very severe). Scores obtained on the Foot Health Status Questionnaire (FHSQ) were compared. This has 13 questions that assess 4 health domains of the feet, namely pain, function, general health and footwear. The stage 4 of HV shown lower scores for the footwear domain (11.23 ± 15.6); general foot health (27.62 ± 19.1); foot pain (44.65 ± 24.5); foot function (53.04 ± 27.2); vigour (42.19 ± 16.8); social capacity (44.46 ± 28.1); and general health (41.15 ± 25.5) compared with stage 1 of HV (P<0.05) and there were no differences of physical activity (62.81 ± 24.6). Often, quality of life decreases in the elderly population based in large part on their foot health. There is a progressive reduction in health in general and foot health with increasing severity of hallux valgus deformity which appears to be associated with the presence of greater degree of HV, regardless of gender.

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    Review Article
    mHealth For Aging China: Opportunities and Challenges
    Sun Jing, Guo Yutao, Wang Xiaoning, Zeng Qiang
    Aging and disease. 2016, 7 (1): 53-67.   DOI: 10.14336/AD.2015.1011
    Abstract   HTML   PDF (874KB) ( 2353 )

    The aging population with chronic and age-related diseases has become a global issue and exerted heavy burdens on the healthcare system and society. Neurological diseases are the leading chronic diseases in the geriatric population, and stroke is the leading cause of death in China. However, the uneven distribution of caregivers and critical healthcare workforce shortages are major obstacles to improving disease outcome. With the advancement of wearable health devices, cloud computing, mobile technologies and Internet of Things, mobile health (mHealth) is rapidly developing and shows a promising future in the management of chronic diseases. Its advantages include its ability to improve the quality of care, reduce the costs of care, and improve treatment outcomes by transferring in-hospital treatment to patient-centered medical treatment at home. mHealth could also enhance the international cooperation of medical providers in different time zones and the sharing of high-quality medical service resources between developed and developing countries. In this review, we focus on trends in mHealth and its clinical applications for the prevention and treatment of diseases, especially aging-related neurological diseases, and on the opportunities and challenges of mHealth in China. Operating models of mHealth in disease management are proposed; these models may benefit those who work within the mHealth system in developing countries and developed countries.

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    Effects of Use and Disuse on Non-paralyzed and Paralyzed Skeletal Muscles
    R. Dolbow David, S. Gorgey Ashraf
    Aging and disease. 2016, 7 (1): 68-80.   DOI: 10.14336/AD.2015.0826
    Abstract   HTML   PDF (712KB) ( 1103 )

    Skeletal muscle is an integral part of the somatic nervous system and plays a primary role in the performance of physical activities. Because physical activity is vital to countering the effects of aging and age related diseases and is a key component in the maintenance of healthy body composition it is important to understand the effects of use and disuse on skeletal muscle. While voluntary muscle activity provides optimal benefits to muscle and the maintenance of healthy body composition, neuromuscular electrical stimulation may be a viable alternative activity for individuals with paralysis. Body composition with a healthy muscle to fat ratio has been associated with healthy blood lipid and glucose profiles that may decrease the risk of cardiovascular and metabolic diseases.

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    Chronic Inflammatory Diseases and Endothelial Dysfunction
    Castellon Xavier, Bogdanova Vera
    Aging and disease. 2016, 7 (1): 81-89.   DOI: 10.14336/AD.2015.0803
    Abstract   HTML   PDF (770KB) ( 1475 )

    Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall’s structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors.

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    Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity
    Luo Xiaoting, Wu Jinzi, Jing Siqun, Yan Liang-Jun
    Aging and disease. 2016, 7 (1): 90-110.   DOI: 10.14336/AD.2015.0702
    Abstract   HTML   PDF (1213KB) ( 2062 )

    Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD+ driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD+ regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications.

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Kunlin Jin, M.D., Ph.D., Professor
Ashok K. Shetty, Ph.D., Professor
David A. Greenberg, M.D., Ph.D., Professor
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