Abstract：
:Estrogens are potent and efficacious neuroprotectants both in vitro and in vivo in a variety of models of neurotoxicity. We determined the structural requirements for neuroprotection in an in vitro assay using a panel of >70 novel estratrienes, synthesized to reduce or eliminate estrogen receptor (ER) binding. We observed that neuroprotection could be enhanced by as much as 200-fold through modifications that positioned a large bulky group at the C2 or C4 position of the phenolic A ring of the estratriene. Further, substitutions on the B, C or D rings either reduced or did not markedly change neuroprotection. Collectively, there was a negative correlation between binding to ERs and neuroprotection with the more potent compounds showing no ER binding. In an in vivo model for neuroprotection, transient cerebral ischemia, efficacious compounds were active in protection of brain tissue from this pro-oxidant insult. We demonstrated that these non-feminizing estrogens engage in a redox cycle with glutathione, using the hexose monophosphate shunt to apply cytosolic reducing potential to cellular membranes. Together, these results demonstrate that non-feminizing estrogens are neuroprotective and protect brain from the induction of ischemic- and Alzheimer's disease (AD)-like neuropathology in an animal model. These features of non-feminizing estrogens make them attractive compounds for assessment of efficacy in AD and stroke, as they are not expected to show the side effects of chronic estrogen therapy that are mediated by ER actions in the liver, uterus and breast.
journal_name
Exp Gerontoljournal_title
Experimental gerontologyauthors
Engler-Chiurazzi EB,Covey DF,Simpkins JWdoi
10.1016/j.exger.2016.10.013subject
Has Abstractpub_date
2017-08-01 00:00:00pages
99-102eissn
0531-5565issn
1873-6815pii
S0531-5565(16)30465-Xjournal_volume
94pub_type
杂志文章,评审abstract：:Cytogenetic analysis of the X chromosome in phytohaemagglutinin stimulated peripheral blood lymphocytes was evaluated in 12 sporadic Alzheimer disease (AD) patients and in 11 healthy subjects. For chromosome analysis two methods were used: (1) standard analysis of G-banded metaphase chromosomes and; (2) fluorescent in...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2004.01.012
更新日期：2004-05-01 00:00:00
abstract：:Physical activity has been associated with alterations in telomere length, a potential indicator of biological aging, but several inconsistencies exist. Our aim was to investigate the associations between physical activity in midlife and leukocyte telomere length (LTL) measured in old age in the Helsinki Businessmen S...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2012.02.003
更新日期：2013-01-01 00:00:00
abstract：:During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and m...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2015.02.016
更新日期：2015-05-01 00:00:00
abstract：:Ethanol ingestion has been implicated in accidental hypothermia of the elderly, but there is no prior data on the relative sensitivity to alcohol of aged homeotherms that might account for disproportionate dysthermia in this age group. To assess their sensitivity, ethanol (0.5-2.0 g/kg) or H20 was given by gavage to s...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(83)90047-5
更新日期：1983-01-01 00:00:00
abstract：:The Tokyo Metropolitan Institute of Gerontology (TMIG) celebrates its 30th anniversary in 2002. Since its establishment, TMIG has been carrying out inter-disciplinary research on aging as a core institute in Japan and functions as a knowledge bank and a source for capable researchers of gerontology. The proportion of ...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/s0531-5565(02)00169-9
更新日期：2002-12-01 00:00:00
abstract：:Lipid hydroperoxides are formed in vivo through free radical pathways from the action of reactive oxygen species on polyunsaturated fatty acids. They are also formed as specific products of lipoxygenases and cyclooxygenases. Homolytic decomposition of lipid hydroperoxides to the alpha,beta-unsaturated aldehyde genotox...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/s0531-5565(01)00133-4
更新日期：2001-09-01 00:00:00
abstract：:The dependent elderly are widely considered to be at higher risk of nutritional problems. Suboptimal micronutrient intake might put the elderly, especially those living in nursing homes, at high risk of morbidity. So far, no public authority, except for the Israel Ministry of Health, has issued particular recommendati...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2016.09.009
更新日期：2016-11-01 00:00:00
abstract：OBJECTIVES:There is a scarcity of data on the association between mild cognitive impairment (MCI) and falls, especially from low- and middle-income countries (LMICs) where 70% of all older adults reside. Thus, we investigated the association between MCI and fall-related injury among older adults residing in six LMICs (...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2020.111222
更新日期：2020-12-29 00:00:00
abstract：:In this study we report the identification of FAH domain containing protein 1 (FAHD1), a recently described member of the fumarylacetoacetate hydrolase (FAH) superfamily of metabolic enzymes, as a novel player in the regulation of cellular senescence. FAHD1 was found in a proteomic screen searching for mitochondrial p...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2017.03.004
更新日期：2017-06-01 00:00:00
abstract：:Diabetes mellitus (DM) is considered a risk factor for the development of Alzheimer disease (AD); however, how DM favors evolution of AD is still insufficiently understood. Hyperglycemia in DM is associated to an increase in mitochondrial reactive oxygen species (ROS) generation, as well as damage of hippocampal cells...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2014.08.008
更新日期：2014-10-01 00:00:00
abstract：:Previous studies have shown that adult mice increase cold-induced heat production as a result of repeated exposures to cold, but that aged mice do not. The objective of the present study was to investigate changes in heat loss during repeated cold exposures in adult and aged C57BL/6J mice. Mice were partially restrain...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/s0531-5565(96)00131-3
更新日期：1997-05-01 00:00:00
abstract：OBJECTIVES:We explored the male-female health-survival paradox in the context of health expectancy (HE) at age 65 and thereafter, using three different morbidity measures and different severity cut-offs with and without adjustments for the share of nursing home residents. METHODS:HE at ages 65, 70, 75, 80, and 85 was ...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2020.111196
更新日期：2021-03-01 00:00:00
abstract：:The aim of the present study was to compare the effects of water-based aerobic training and water-based resistance training on muscular strength and cardiorespiratory fitness in older women. Sixty-nine individuals were randomized into the following three groups: the water-based aerobic training (WA, n = 23) group, the...
journal_title：Experimental gerontology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.exger.2018.04.022
更新日期：2018-07-15 00:00:00
abstract：:Life table aging rate (LAR) is defined as the age-specific rate of mortality change with age and corresponds to the first derivative or slope of the mortality schedule at each age. We computed the sex-specific LARs for 167 Medfly cohorts, containing a total of approximately 600,000 individuals of each sex. We found th...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(94)00041-z
更新日期：1995-05-01 00:00:00
abstract：:Increased lifespan can be associated with greater resistance to many different stressors, most notably thermal stress. Such hormetic effects have also been found in C. elegans where short-term exposure to heat lengthens the lifespan. Genetic investigations have been carried out using mutation perturbations in a single...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2012.05.005
更新日期：2012-08-01 00:00:00
abstract：:We investigated the effect of resistance training on irisin expression with improvement in muscle strength and function in aged mice and human. In the mice study, 19 months old male C57BL/6 mice were randomly assigned into two groups; control group and resistance exercise group. Ladder climbing exercise with tail weig...
journal_title：Experimental gerontology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.exger.2015.07.006
更新日期：2015-10-01 00:00:00
abstract：:Despite general belief that the mechanical properties of bone material contribute to whole bone strength, it is still obscure what the age effects are on mechanical behavior of the bone material, particularly in the case of the femoral neck trabeculae. In this study, atomic force microscopy was used for imaging and me...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2011.11.011
更新日期：2012-02-01 00:00:00
abstract：:Aging plays an important role in increased vulnerability to atrial fibrillation (AF). Mediated by activity at the muscarinic type 2 receptor (M2R), the parasympathetic nerve contributes to the onset of AF. The purpose of this study was to investigate whether aging changes the distribution of M2R in the atrial myocardi...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2009.06.002
更新日期：2009-09-01 00:00:00
abstract：:Androgen levels decrease with aging in men. Androgen deficiency in elderly men may lead to asthenia, decrease in muscle mass, osteoporosis, decrease in sexual activity, and, in some cases, changes in mood and cognitive function. Combination of these factors may result in impaired quality of life in the elderly male. A...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/0531-5565(93)90069-p
更新日期：1993-07-01 00:00:00
abstract：:Changes associated with the age-related decline of physiological functions, and their relation with mortality rates, are thoroughly being investigated in the aging research field. We used the Mediterranean fruit fly Ceratitis capitata, largely studied by biodemographers, as a model for functional senescence studies. T...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2012.04.001
更新日期：2012-06-01 00:00:00
abstract：:Accumulation of myeloid-derived suppressor cells (MDSCs) in aged hosts contribute to the age-related increase of susceptibility to murine breast adenocarcinoma and co-stimulatory molecules expressed in MDSCs are essential for MDSCs-mediated immune suppression. However, the co-stimulatory molecules that exert a direct ...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2014.12.001
更新日期：2015-01-01 00:00:00
abstract：BACKGROUND:Fatigue resistance (FR) was here defined as the time during which grip strength (GS) drops to 50% of its maximum during sustained contraction. Since different GS systems exist, we compared FR obtained with Pneumatic (Pneu) and Hydraulic (Hydr) handgrip systems. Hand pain induced by both systems was also inve...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2020.110950
更新日期：2020-07-15 00:00:00
abstract：:There is growing concern over the increasing instances of decline in cognitive abilities with aging in humans. The present study evaluated the benefits of the natural antioxidant, grape seed proanthocyanidin extract (GSPE) in treating the effects of age-related oxidative stress (OS) and accumulation of lipofuscin (LF)...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2011.08.006
更新日期：2011-11-01 00:00:00
abstract：:Intrinsic exercise capacity is predictive of both lifespan and healthspan but whether adaptive exercise capacity influences the benefits achieved from aerobic training implemented later in life is not known. AIM:To determine if exercise late in life provides any functional improvements or underlying beneficial bioche...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2019.110657
更新日期：2019-10-01 00:00:00
abstract：:Evolutionary aspects of menopause are considered from several perspectives. First, the programmed exhaustion of ovarian oocytes appears to be a general trait of mammals that is not as widely found in other vertebrates. Second, studies on mice suggest that the maternal age effect that accelerates the incidence of Down ...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/0531-5565(94)90009-4
更新日期：1994-05-01 00:00:00
abstract：OBJECTIVES:To evaluate the effects of elastic band resistance training in combination with nutrient supplementation on muscular strength and the ability to perform mobility-related activities of daily living in older adults living in retirement care facilities. DESIGN:Randomized controlled trial, with a 6-month interv...
journal_title：Experimental gerontology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.exger.2015.08.013
更新日期：2015-12-01 00:00:00
abstract：:This study was designed to investigate whether the relationship of fiber size and force is maintained with aging and inactivity. We hypothesized that fiber size and fiber force-generating capacity would decrease in parallel, thus resulting in no change in specific force with either age or inactivity. Thirty male Fisch...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2004.12.002
更新日期：2005-03-01 00:00:00
abstract：:Maintaining physical mobility is important for preventing age-related comorbidities in older adults. Endurance and resistance training prevent mobility loss in aging, but exercise alone does not always achieve the expected improvements in physical and cardiopulmonary function. Recent preclinical evidence suggests that...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2020.110972
更新日期：2020-08-01 00:00:00
abstract：:Post-viral pneumococcal pneumonia is a leading morbidity and mortality in older patients (≥65years of age). The goal of our current study is to understand the impact of chronological aging on innate immune responses to a secondary, post viral infection with Streptococcus pneumoniae, a causative agent of bacterial pneu...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2017.11.010
更新日期：2018-05-01 00:00:00
abstract：:It is now widely recognized that in order to optimize bone health in the later years, bone healthy behaviors should begin at a young age and continue throughout life. Prescribed orally to lower lipid levels in adults of all ages, statins have also been shown to stimulate bone formation in vitro by promoting bone morph...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2013.04.007
更新日期：2013-08-01 00:00:00
