scholarly journals The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1269
Author(s):  
Ramy K. A. Sayed ◽  
Marisol Fernández-Ortiz ◽  
Ibtissem Rahim ◽  
José Fernández-Martínez ◽  
Paula Aranda-Martínez ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Nlrp3 Inflammasome ◽  
Multivesicular Bodies ◽  
Protective Effects ◽  
Cardiac Damage ◽  
Cardiac Aging ◽  
Age Related ◽  
Cardiac Muscles ◽  
The Impact ◽  
Age Related Changes

To investigate the role of NLRP3 inflammasome in cardiac aging, we evaluate here morphological and ultrastructural age-related changes of cardiac muscles fibers in wild-type and NLRP3-knockout mice, as well as studying the beneficial effect of melatonin therapy. The results clarified the beginning of the cardiac sarcopenia at the age of 12 months, with hypertrophy of cardiac myocytes, increased expression of β-MHC, appearance of small necrotic fibers, decline of cadiomyocyte number, destruction of mitochondrial cristae, appearance of small-sized residual bodies, and increased apoptotic nuclei ratio. These changes were progressed in the cardiac myocytes of 24 old mice, accompanied by excessive collagen deposition, higher expressions of IL-1α, IL-6, and TNFα, complete mitochondrial vacuolation and damage, myofibrils disorganization, multivesicular bodies formation, and nuclear fragmentation. Interestingly, cardiac myocytes of NLRP3−/− mice showed less detectable age-related changes compared with WT mice. Oral melatonin therapy preserved the normal cardiomyocytes structure, restored cardiomyocytes number, and reduced β-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies’ formation, and decreased expressions of β-MHC, IL-1α, and IL-6. Fewer cardiac sarcopenic changes and highly remarkable protective effects of melatonin treatment detected in aged cardiomyocytes of NLRP3−/− mice compared with aged WT animals, confirming implication of the NLRP3 inflammasome in cardiac aging. Thus, NLRP3 suppression and melatonin therapy may be therapeutic approaches for age-related cardiac sarcopenia.

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 Estrogen Receptor and Vascular Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Morgane Davezac ◽  
Melissa Buscato ◽  
Rana Zahreddine ◽  
Patrick Lacolley ◽  
Daniel Henrion ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cardiovascular Diseases ◽  
Experimental Studies ◽  
Hormonal Treatment ◽  
Protective Effects ◽  
Age Related ◽  
Nuclear Receptor Family ◽  
The Impact ◽  
Receptor Family

Cardiovascular diseases remain an age-related pathology in both men and women. These pathologies are 3-fold more frequent in men than in women before menopause, although this difference progressively decreases after menopause. The vasculoprotective role of estrogens are well established before menopause, but the consequences of their abrupt decline on the cardiovascular risk at menopause remain debated. In this review, we will attempt to summarize the main clinical and experimental studies reporting the protective effects of estrogens against cardiovascular diseases, with a particular focus on atherosclerosis, and the impact of aging and estrogen deprivation on their endothelial actions. The arterial actions of estrogens, but also part of that of androgens through their aromatization into estrogens, are mediated by the estrogen receptor (ER)α and ERβ. ERs belong to the nuclear receptor family and act by transcriptional regulation in the nucleus, but also exert non-genomic/extranuclear actions. Beside the decline of estrogens at menopause, abnormalities in the expression and/or function of ERs in the tissues, and particularly in arteries, could contribute to the failure of classic estrogens to protect arteries during aging. Finally, we will discuss how recent insights in the mechanisms of action of ERα could contribute to optimize the hormonal treatment of the menopause.

scholarly journals The Impact of Long‐Term Physical Activity on Age‐Related Changes in Protein and Gene Expression

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ian R Lanza ◽  
Daniel K Short ◽  
Kevin R Short ◽  
Yan W Asmann ◽  
Sreekumar Raghavakaimal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Age Related ◽  
The Impact ◽  
Age Related Changes

A systems analysis of age-related changes in some cardiac aging traits

2013 ◽  
Vol 15 (2) ◽  
pp. 139-152 ◽  
Author(s):  
D. R. Govindaraju ◽  
K. M. Pencina ◽  
D. S. Raj ◽  
J. M. Massaro ◽  
B. A. Carnes ◽  
...  
Keyword(s):  
Systems Analysis ◽  
Cardiac Aging ◽  
Age Related ◽  
Age Related Changes

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

2005 ◽  
Vol 62 (3) ◽  
pp. 293-298 ◽  
Author(s):  
G. Casadesus ◽  
C. S. Atwood ◽  
X. Zhu ◽  
A. W. Hartzler ◽  
K. M. Webber ◽  
...  
Keyword(s):  
Reproductive Hormones ◽  
Age Related ◽  
The Impact ◽  
Age Related Changes

scholarly journals Slc6a3-dependent expression of a CAPS-associated Nlrp3 allele results in progressive behavioral abnormalities and neuroinflammation in aging mice 

2020 ◽  
Author(s):  
Katharine M von Herrmann ◽  
Faith L Anderson ◽  
Eileen M Martinez ◽  
Alison L Young ◽  
Matthew C Havrda
Keyword(s):  
Motor Function ◽  
Nlrp3 Inflammasome ◽  
Dopaminergic Neurons ◽  
Dopaminergic Neuron ◽  
Molecular Mechanisms ◽  
Activating Mutations ◽  
Age Related ◽  
Neurologic Disorders ◽  
The Impact ◽  
Inflammasome Activity

Abstract Background : An association between neuroinflammation and age-related neurologic disorders has been established but the molecular mechanisms and cell types involved have not been thoroughly characterized. Activity of the proinflammatory NLRP3 inflammasome is implicated in Alzheimer’s and Parkinson’s disease and our recent studies in patients suggest that dopaminergic neurons within the degenerating mesencephalon express NLRP3 throughout the progression of PD. Here, we directly test the impact of enhanced inflammasome activity in mesencephalic neurons by characterizing motor function, tissue integrity, and neuroinflammation in aging mice harboring hyper-activating mutations within the endogenous murine Nlrp3 locus, enabled only in cells expressing the dopaminergic neuron specific Slc6a3 promoter. Methods: We compared mice harboring inducible alleles encoding the cryopyrin-associated periodic syndrome activating mutations Nlrp3A350V and Nlrp3L351P inserted into the endogenous mouse Nlrp3 locus. Tissue specific expression was driven by breeding these animals with mice expressing Cre recombinase under the control of the dopaminergic neuron specific Slc6a3 promoter. The experimental mice, designed to express hyperactive NLRP3 only when the endogenous mouse Nlrp3 promotor is active in dopaminergic neurons, were analyzed throughout 18 months of aging using longitudinal motor function assessments. Biochemical and histologic analyses of mesencephalic tissues were conducted in 1- and 18-month old animals.Results : We observed progressive and significant deficits in motor function in animals expressing Nlrp3L351P, compared with animals expressing Nlrp3WT and Nlrp3A350V. Age-dependent neuroinflammatory changes in the mesencephalon were noted in all animals. Analysis of GFAP-immunoreactive astrocytes in the substantia nigra revealed a significant increase in astrocyte number in animals expressing Nlrp3L351P compared with Nlrp3WT and Nlrp3A350V. Further analysis of Nlrp3L351P striatal tissues indicated genotype specific gliosis, elevated Il1b expression, and both morphologic and gene expression indicators of proinflammatory A1 astrocytes.Conclusions : Dopaminergic neurons have the potential to accumulate NLRP3 inflammasome activators with age, including reactive oxygen species, dopamine metabolites, and misfolded proteins. Results indicate the Nlrp3 locus is active in dopaminergic neurons in aging mice, and that the hyperactive Nlrp3L351P allele can drive neuroinflammatory changes in association with progressive behavioral deficits. Findings suggest neuronal NLRP3 inflammasome activity may contribute to neuroinflammation observed during normal aging and the progression of neurologic disorders.

Aging Processes in the Subcortical Auditory System

2018 ◽  
pp. 638-680 ◽  
Author(s):  
Donald M. Caspary ◽  
Daniel A. Llano
Keyword(s):  
Hearing Loss ◽  
Auditory System ◽  
De Novo ◽  
Auditory Brainstem ◽  
Superior Olivary Complex ◽  
Age Related ◽  
Medial Geniculate ◽  
Age Related Hearing Loss ◽  
The Impact ◽  
Age Related Changes

As arguably the third most common malady of industrialized populations, age-related hearing loss is associated with social isolation and depression in a subset of the population that will approach 25% by 2050. Development of behavioral or pharmacotherapeutic approaches to prevent or delay the onset of age-related hearing loss and mitigate the impact of hearing loss of speech understanding requires a better understanding of age-related changes that occur in the central auditory processor. This chapter critically reviews and discusses changes that occur in the auditory brainstem and thalamus with increased age. It briefly discusses age-related cellular changes that occur de novo within the central auditory system versus deafferentation plasticity and animal models of aging. Subsections discuss the cochlear nucleus, superior olivary complex, inferior colliculus, and the medial geniculate body with an emphasis on age-related changes in neurotransmission and how these changes could underpin the observed loss of precise temporal processing with increased age.

The Relevance of Cognitive Aging Research to Warning Label Design

1997 ◽  
Vol 41 (2) ◽  
pp. 1368-1368
Author(s):  
Gabriel K. Rousseau ◽  
Nina Lamson ◽  
Wendy A. Rogers
Keyword(s):  
Older Adults ◽  
Cognitive Abilities ◽  
Cognitive Aging ◽  
Color Discrimination ◽  
Warning Label ◽  
Aging Research ◽  
Individual Difference Variables ◽  
Age Related ◽  
The Impact ◽  
Age Related Changes

A variety of individual difference variables affect whether someone notices, encodes, comprehends, and complies with a product warning label. Failures at any of these stages reduce the effectiveness of warnings. Development of effective warnings must be based on understanding the characteristics of the product user. As the population grows older, consideration of age-related changes in perceptual and cognitive abilities becomes more relevant to the warning designer. Aging researchers have identified a variety of declines and changes in vision (e.g., acuity, contrast sensitivity, and color discrimination) and memory (e.g., working memory and prospective memory). By considering the abilities of the product user, the impact of age-related changes may be minimized. Based on cognitive aging research and theory, we will make recommendations about how designers can increase the effectiveness of warnings for older adults.

Problems of the Accumulation of Human Capital by Employed Workers in Modern Russia

2021 ◽  
Vol 9 (1) ◽  
pp. 59-63
Author(s):  
Elena Basovskaya
Keyword(s):  
Human Capital ◽  
Older Workers ◽  
Work Experience ◽  
Positive Experience ◽  
Highly Qualified ◽  
Institutional Conditions ◽  
Age Related ◽  
Implementation Of Innovations ◽  
The Impact ◽  
Age Related Changes

The paper analyzes the accumulation of human capital by the employed popula-tion of modern Russia, depending on age, work experience and profession. The influ-ence of the age and seniority of workers on the amount of wages assessed as character-istics of the human capital of workers. For the analysis, we used Rosstat data on the amount of remuneration of workers of different professions, of different ages, with dif-ferent work experience for the period 2005-2019. It found that the nature of the age-related changes in wages during the period under review approached the nature of the age-related changes in wages in OECD countries, which demonstrates the resumption of growth in the wages of older workers. This indicates an increase in the efficiency of the human capital of older workers, which be explained the development of creative abilities based on the accumulated positive experience. This phenomenon is inherent, mainly, in managers and highly qualified specialists. The impact of experience on the accumulation of human capital in the period from 2005-2019 has been steadily decreasing, which indicates a low level of implementation of innovations in the economy and limited economic growth due to unfavorable institutional conditions.

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