Estrogenic Regulation of Neuroprotection and Inflammation in Ischemic Stroke and Aging

2020 ◽  
pp. 416-432
Author(s):  
Farida Sohrabji ◽  
Shameena Bake ◽  
Amutha Selvamani
Keyword(s):  
Ischemic Stroke ◽  
Older Women ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Aging Brain ◽  
Younger Women ◽  
Young Females ◽  
Age Related ◽  
Aging Populations ◽  
Age Related Changes

Stroke is the fifth leading cause of mortality and the major cause of long-term disability in the United States. Epidemiological studies report sex differences in ischemic stroke occurrence, mortality and functional recovery. In younger demographics, the overall incidence of stroke is higher in men than younger women, but in the elderly population, stroke rates are higher in older women compared to age-matched men, indicating an interaction of age and sex as important modifiers of disease. The increased risk for stroke in older women is attributed to loss of ovarian hormones, principally estrogens. However, estrogen/estradiol therapy is not always neuroprotective for stroke, especially in aging populations. Age-related changes in central and peripheral immune cells and the blood–brain barrier may play a crucial role in modifying stroke outcomes and the effects of estrogens. This chapter discusses the role of estrogens as a stroke protectant in younger females in contrast to its anomalous effects in the aging brain. Furthermore, the chapter describes age-related changes in support cells in the brain and in the periphery and evaluates the evidence that age-associated inflammation underlies the switch in estrogens neuroprotective action in young females to its neurotoxic effects in older females.

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

scholarly journals Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review

Gerontology ◽  
2017 ◽  
Vol 63 (6) ◽  
pp. 580-589 ◽  
Author(s):  
Juan Diego Naranjo ◽  
Jenna L. Dziki ◽  
Stephen F. Badylak
Keyword(s):  
Regenerative Medicine ◽  
Treatment Options ◽  
The Elderly ◽  
Signaling Molecules ◽  
Current Treatment ◽  
Muscle Physiology ◽  
Age Related ◽  
Increased Risk ◽  
And Function ◽  
Age Related Changes

Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.

Neuroimaging Approaches for Elderly Studies

2017 ◽  
pp. 1576-1617
Author(s):  
Charis Styliadis ◽  
Panagiotis Kartsidis ◽  
Evangelos Paraskevopoulos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structure And Function ◽  
Cognitive Capacity ◽  
Aging Brain ◽  
Cerebral Structure ◽  
Age Related ◽  
Elderly Populations ◽  
And Function ◽  
Age Related Changes

Advances in the field of neuroimaging have allowed for the examination of the effects of age-related changes on cognitive capacity in elderly populations. Structural techniques are now routinely used to report cortical atrophic rates in aging and particularly within the context of the Alzheimer's disease, and may be integrated with functional techniques which examine the functional characteristics of the cortex at rest and during the performance of a task. Despite advancing age cognitive function remains highly plastic, allowing for interventions that aim to maintain or even remediate its capacity and the mechanisms by which structure and function are altered among seniors. Overall, information on the integrity of the cerebral structure and function aid in the early detection and treatment of the Alzheimer's disease as well as the evaluation and track of the disease's progression. In this chapter, neuroimaging methods are presented along with findings that are particularly relevant for the study of neuroplasticity in the aging brain.

Age-related changes in intestinal permeability and gut microbiota after ischemic stroke

2014 ◽  
Vol 275 (1-2) ◽  
pp. 97
Author(s):  
Joshua Crapser ◽  
Rodney Ritzel ◽  
Sarah Doran ◽  
Edward Koellhoffer ◽  
Anita Patel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Age Related ◽  
Age Related Changes

scholarly journals Bone and Muscle Crosstalk in Aging

2020 ◽  
Vol 8 ◽  
Author(s):  
Chen He ◽  
Wenzhen He ◽  
Jing Hou ◽  
Kaixuan Chen ◽  
Mei Huang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Bone Mineral Density ◽  
Skeletal Muscle ◽  
Bone Cells ◽  
The Elderly ◽  
Extracellular Vesicle ◽  
Mineral Density ◽  
Age Related ◽  
Age Related Changes

Osteoporosis and sarcopenia are two age-related diseases that affect the quality of life in the elderly. Initially, they were thought to be two independent diseases; however, recently, increasing basic and clinical data suggest that skeletal muscle and bone are both spatially and metabolically connected. The term “osteosarcopenia” is used to define a condition of synergy of low bone mineral density with muscle atrophy and hypofunction. Bone and muscle cells secrete several factors, such as cytokines, myokines, and osteokines, into the circulation to influence the biological and pathological activities in local and distant organs and cells. Recent studies reveal that extracellular vesicles containing microRNAs derived from senescent skeletal muscle and bone cells can also be transported and aid in regulating bone-muscle crosstalk. In this review, we summarize the age-related changes in the secretome and extracellular vesicle-microRNAs secreted by the muscle and bone, and discuss their interactions between muscle and bone cells during aging.

scholarly journals The Limbic Degradation of Aging Brain: A Quantitative Analysis with Diffusion Tensor Imaging

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hediye Pınar Gunbey ◽  
Karabekir Ercan ◽  
Ayşe Serap Fındıkoglu ◽  
H. Taner Bulut ◽  
Mustafa Karaoglanoglu ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Limbic System ◽  
Diffusion Tensor ◽  
Normal Population ◽  
Parahippocampal Gyrus ◽  
Aging Brain ◽  
Emotional Life ◽  
Age Related ◽  
Left Hippocampus ◽  
Age Related Changes

Introduction. The limbic system primarily responsible for our emotional life and memories is known to undergo degradation with aging and diffusion tensor imaging (DTI) is capable of revealing the white matter integrity. The aim of this study is to investigate age-related changes of quantitative diffusivity parameters and fiber characteristics on limbic system in healthy volunteers.Methods. 31 healthy subjects aged 25–70 years were examined at 1,5 TMR. Quantitative fiber tracking was performed of fornix, cingulum, and the parahippocampal gyrus. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements of bilateral hippocampus, amygdala, fornix, cingulum, and parahippocampal gyrus were obtained as related components.Results. The FA values of left hippocampus, bilateral parahippocampal gyrus, and fornix showed negative correlations with aging. The ADC values of right amygdala and left cingulum interestingly showed negative relation and the left hippocampus represented positive relation with age. The cingulum showed no correlation. The significant relative changes per decade of age were found in the cingulum and parahippocampal gyrus FA measurements.Conclusion. Our approach shows that aging affects hippocampus, parahippocampus, and fornix significantly but not cingulum. These findings reveal age-related changes of limbic system in normal population that may contribute to future DTI studies.

Anabolic Hormones in Aging Women: Effects of Supplementation vs. Physical Activity

2004 ◽  
Vol 29 (1) ◽  
pp. 76-89 ◽  
Author(s):  
Jennifer L. Copeland
Keyword(s):  
Physical Activity ◽  
Bone Mass ◽  
Physical Function ◽  
Older Women ◽  
Hormone Replacement ◽  
Endocrine System ◽  
Anabolic Hormones ◽  
Age Related ◽  
Aging Women ◽  
Age Related Changes

Aging is associated with a decline in bone mass, muscle mass, strength, and physical function, and women are more likely to suffer from these physical changes than men. The model presented in this paper illustrates the age related changes in anabolic hormones and how this may partly explain the diminished physical function of older women. The model can also be used to identify potential sites of intervention that could delay the atrophy of the musculoskeletal system. Various pharmacological hormone therapies have been shown to be beneficial, but there may be health risks associated with their use. There is evidence that regular physical activity is related to higher levels of anabolic hormones in older persons, therefore exercise could be an alternative to drugs for slowing the age related changes in the endocrine system. However, some research suggests that the hormone response to exercise is blunted in older women. This lower hormonal response may not be a consequence of aging per se but instead may result from secondary characteristics of aging such as a decline in physical fitness and exercise intensity or changes in body composition. Further research is needed to determine whether exercise-induced increases in endogenous hormones have clinical significance in improving muscle or bone mass in aging women. Key words: hormone replacement therapy, exercise, sex steroids, growth hormone, IGF-I

Non-Nutritive Bioactive Food Constituents of Plants: Lycopene, Lutein and Zeaxanthin

2003 ◽  
Vol 73 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Sies ◽  
Stahl
Keyword(s):  
The Elderly ◽  
Epidemiological Studies ◽  
Age Related Macular Degeneration ◽  
Carotenoid Pigments ◽  
Daily Consumption ◽  
Singlet Molecular Oxygen ◽  
Protective Mechanisms ◽  
Tomato Paste ◽  
Age Related ◽  
Yellow Color

Lycopene, lutein, and zeaxanthin are major carotenoids in human blood and tissues but unlike b-carotene do not contribute to vitamin A supply. These carotenoids are efficient antioxidants quenching singlet molecular oxygen which is formed in photooxidative processes and thus may contribute to the prevention of light-exposed tissue, skin and eyes, from light-induced damage. Increasing lycopene intake by daily consumption of tomato paste over a period of ten weeks provides protection against erythema formation following UV-irradiation. Lycopene and other carotenoids may be used as oral sun protectants and contribute to the maintenance of skin health. The yellow color of the macula lutea is due to the presence of the carotenoid pigments lutein and zeaxanthin. These macula carotenoids are suggested to play a role in protection against light-dependent damage. Filtering of blue light and scavenging of reactive intermediates generated in photooxidation are considered to be the underlying protective mechanisms. Epidemiological studies provide evidence that an increased consumption of lutein is associated with a lowered risk for age-related macular degeneration, a disease with increasing incidence in the elderly.

Sex differences in the perceived intensity of breathlessness during exercise with advancing age

2008 ◽  
Vol 104 (6) ◽  
pp. 1583-1593 ◽  
Author(s):  
Dror Ofir ◽  
Pierantonio Laveneziana ◽  
Katherine A. Webb ◽  
Yuk-Miu Lam ◽  
Denis E. O'Donnell
Keyword(s):  
Sex Differences ◽  
Older Women ◽  
Cross Sectional Study ◽  
Inspiratory Muscle ◽  
Cross Sectional ◽  
Respiratory Impairment ◽  
Mechanical Constraints ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Age Related Changes

The prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40–80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (V̇o2) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (V̇e), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (Vt) to dynamic inspiratory capacity (IC) (all P < 0.05). These changes were quantitatively similar in women ( n = 39) and in men ( n = 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished ( P = 0.05), as exercise ventilation increased relative to capacity ( P = 0.013) and as the Vt/IC ratio increased ( P = 0.003) during exercise. Older women (60–80 yr old, n = 23) reported greater ( P < 0.05) intensity of exertional breathlessness at a standardized V̇o2 and V̇e than age-matched men ( n = 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on Vt expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve.

scholarly journals Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 332-332
Author(s):  
Ranran Zhai ◽  
Timothy Pyrkov ◽  
Anastasia Shindyapina ◽  
Marco Mariotti ◽  
Peter Fedichev ◽  
...  
Keyword(s):  
Immune Cell ◽  
The Elderly ◽  
Significant Negative Correlation ◽  
Epidemiological Studies ◽  
Notch Signaling Pathway ◽  
Biological Age ◽  
Risk Of Death ◽  
Age Related ◽  
Increased Risk ◽  
Clock Models

Abstract Epidemiological studies revealed that the elderly and those with comorbidities are most susceptible to COVID-19. To understand how genetics affects the risk of COVID-19, we conducted a multi-instrument Mendelian Randomization (MR) analysis and found that the genetic variation that supports a longer life is significantly associated with the lower risk of COVID-19 infection, as well as being hospitalized after infected. The odds ratio is 0.31 (P = 9.7e-6) and 0.46 (P = 3.3e-4), respectively, per additional 10 years of life. We further applied aging clock models and detected an association between biological age acceleration and future incidence and severity of COVID-19 infection for all subjects and individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. A bivariate genomic scan for age-related COVID-19 infection identified a key contribution of the Notch signaling pathway and immune system. Finally, we performed MR using 389 immune cell traits as exposure and observed a significant negative correlation between their effect on lifespan and COVID-19 risk, especially for B cell-related traits. More specifically, we discovered the lower CD19 level on B cells indicates an increased risk of COVID-19 and potentially decreases the lifespan expectancy, which is further validated in clinical data from COVID-19 patients. Our analysis suggests that the factors that accelerate aging and limit lifespan cause an increased COVID-19 risk. Thus, the interventions target these factors (e.g., reduce biological age), after further validation, may have the opportunity to reduce the risk of COVID-19.

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