scholarly journals Altered expression of hepatic β-adrenergic receptors in aging rats: implications for age-related metabolic dysfunction in liver

2018 ◽  
Vol 314 (4) ◽  
pp. R574-R583 ◽  
Author(s):  
Yun Shi ◽  
Zhen-Ju Shu ◽  
Hanzhou Wang ◽  
Jeffrey L. Barnes ◽  
Chih-Ko Yeh ◽  
...  
Keyword(s):  
Rat Liver ◽  
Radioligand Binding ◽  
Adult Life ◽  
Receptor Subtypes ◽  
Binding Studies ◽  
Adult Life Span ◽  
Altered Expression ◽  
Aging Rats ◽  
Age Related ◽  
Glucose Output

Increased β-adrenergic receptor (β-AR)-mediated activation of adenylyl cyclase (AC) in rat liver during aging has been linked to age-related increases in hepatic glucose output and hepatosteatosis. In this study, we investigated the expression of β-ARs, individual receptor subtypes, and G protein-coupled receptor (GPCR) regulatory proteins in livers from aging rats. Radioligand-binding studies demonstrated that β-AR density increased by greater than threefold in hepatocyte membranes from senescent (24-mo-old) compared with young adult (7-mo-old) rats and that this phenomenon was blocked by food restriction, which is known to retard aging processes in rodents. Competition-binding studies revealed a mixed population of β1- and β2-AR subtypes in liver membranes over the adult life span, with a trend for greater β2-AR density with age. Expression of both β-AR subtype mRNAs in rat liver increased with age, whereas β2- but not β1-AR protein levels declined in livers of old animals. Immunoreactive β2- but not β1-ARs were preferentially distributed in pericentral hepatic regions. Levels of GRK2/3 and β-arrestin 2 proteins, which are involved in downregulation of agonist-activated GPCRs, including β-ARs, increased during aging. Insofar as sympathetic tone increases with age, our findings suggest that, despite enhanced agonist-mediated downregulation of hepatic β-ARs preferentially affecting the β2-AR subtype, increased generation of both receptor subtypes during aging augments the pool of plasma membrane-bound β-ARs coupled to AC in hepatocytes. This study thus identifies one or both β-AR subtypes as possible therapeutic targets involved in aberrant hepatic processes of glucose and lipid metabolism during aging.

Bronchospasmolytic and Adenosine Binding Activity of 8- (Proline / Pyrazole)-Substituted Xanthine Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Sneha Singh ◽  
Madhwi Ojha ◽  
Divya Yadav ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Radioligand Binding ◽  
Binding Activity ◽  
Receptor Subtypes ◽  
Significant Protection ◽  
Binding Studies ◽  
Standard Drug ◽  
Xanthine Derivatives ◽  
Radioligand Binding Studies ◽  
Micromolar Range

Background: ABSTRACT: Background: 8-Phenyltheophylline derivatives exhibit prophylactic effects at a specific dose but do not produce the cardiovascular or emetic side effects associated with xanthines, thereby exhibiting unique characteristics of potential therapeutic importance. Methods: Novel series of 8-(proline/pyrazole)-substituted xanthine analogs has been synthesized. The affinity and selectivity of compounds to adenosine receptors have been assessed by radioligand binding studies. The synthesized compounds also showed good bronchospasmolytic properties (increased onset of bronchospasm; decreased duration of jerks) with 100% survival of animals in comparison to the standard drug. Besides, compound 8f & 9f showed good binding affinity in comparison to other synthesized compounds in the micromolar range. Results: The maximum binding affinity of these compounds was observed for A2B receptors, which is ~ 7 or 10 times higher as compared to A1, A2A and A3 receptors. The newly synthesized derivatives 8f, 9a-f, 17g-m, and 18g-m displayed significant protection against histamine aerosol induced bronchospasm in guinea pigs. Conclusion: Newly synthesized proline/pyrazole based xanthines compounds showed a satisfactory binding affinity for adenosine receptor subtypes. Replacement or variation of substituted proline ring with substituted pyrazole scaffold at 8thposition of xanthine moiety resulted in the reduction of adenosine binding affinity and bronchospasmolytic effects.

scholarly journals Mechanisms of age-related decline in memory search across the adult life span.

2013 ◽  
Vol 49 (12) ◽  
pp. 2396-2404 ◽  
Author(s):  
Thomas T. Hills ◽  
Rui Mata ◽  
Andreas Wilke ◽  
Gregory R. Samanez-Larkin
Keyword(s):  
Life Span ◽  
Adult Life ◽  
Memory Search ◽  
Adult Life Span ◽  
Age Related

scholarly journals Human Adrenal Cortical Zone Changes With Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A69-A69
Author(s):  
Yuta Tezuka ◽  
Nanako Atsumi ◽  
Amy Blinder ◽  
Juilee Rege ◽  
Thomas J Giordano ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Adult Life ◽  
Rank Correlation ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Strong Positive Correlation ◽  
Adult Life Span ◽  
Functional Changes ◽  
Morphological Studies ◽  
Age Related

Abstract Background: Previous adrenal morphological studies have shown that the zona reticularis (ZR) and the zona glomerulosa (ZG) decrease in size with aging. Although several lines of evidence indicate that the hypothalamic-pituitary-adrenal axis becomes hyperactive in elderly, little is known about age-related transformations of the adrenal zona fasciculata (ZF). Objectives: To investigate the morphological and functional changes of the adrenal cortex across the adult life span, with emphasis on: 1) the understudied ZF, and 2) potential sexual dimorphisms. Methods: We used immunohistochemistry to evaluate the expression of several cortical proteins: aldosterone synthase (CYP11B2), visinin-like protein 1 (VSNL1), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 11β-hydroxylase (CYP11B1) and cytochrome b5 type A (CYB5A). The ZF area was estimated by subtracting the VSNL1-positive (a ZG marker) area from the HSD3B2-expressing area (ZG and ZF). All captured images were quantitated by ImageJ. In addition, we employed liquid chromatography-tandem mass spectrometry to quantify the morning serum concentrations of 6 steroids: cortisol, 11-deoxycortisol (11dF), 17α-hydroxyprogesterone (17OHP4), 11-deoxycorticosterone (DOC), corticosterone, and androstenedione (A4). The Mann-Whitney U test and Spearman’s rank correlation coefficients were used for statistical analysis, as appropriate. Results: We included 60 adrenal glands from 30 men and 30 women, with ages between 18–86 years. The total cortical area was positively correlated with age (r=0.34, p=0.008), and this association was significant only in men (p=0.02). Both the total (VSNL1-positive) and functional ZG (CYP11B2-positive) areas declined abruptly with aging in men (r=-0.57 and -0.76, p=0.001 and p<0.0001, respectively), but not women (p=0.06 and 0.27, respectively). The CYB5A-positive area, marking the ZR, correlated negatively with age (r=-0.76, p<0.0001) in both sexes. In contrast, the estimated ZF area showed a strong positive correlation with age both in men (r=0.59, p=0.0006) and women (r=0.49, p=0.007), while CYP11B1-positive area remained stable across ages (p=0.86). Finally, we measured morning levels of 6 steroids in 149 men and 149 women, with ages between 21–95 years, matched for age and body mass index. Serum cortisol, corticosterone, and DOC levels remained relatively stable across ages (p=0.38, 0.64 and 0.25, respectively), while 11dF levels increased slightly with age (r=0.16 and p=0.007), particularly so in men (p=0.005). Expectedly, 17OHP4 and A4 declined with aging (r=-0.37 and -0.37, p<0.0001 for both). Conclusions: In contrast with the ZG and ZR, the ZF and the total adrenal cortex area enlarge with aging. An abrupt decline of the ZG occurs with age in men, but not in women, possibly contributing to sexual dimorphism in cardiovascular risk.

scholarly journals Temporal clusters of age-related behavioral alterations captured in smartphone touchscreen interactions

2021 ◽  
Author(s):  
Enea Ceolini ◽  
Ruchella Kock ◽  
Gijsbert Stoet ◽  
Guido Band ◽  
Arko Ghosh
Keyword(s):  
Real World ◽  
Temporal Dynamics ◽  
Probability Distributions ◽  
Adult Life ◽  
Cognitive Tests ◽  
Behavioral Alterations ◽  
Adult Life Span ◽  
Adult Lifespan ◽  
Age Related ◽  
Common Notion

Cognitive and behavioral abilities alter across the adult life span. Smartphones engage various cognitive functions and the corresponding touchscreen interactions may help resolve if and how the behavior is systematically structured by aging. Here, in a sample spanning the adult lifespan (16 to 86 years, N = 598, accumulating 355 million interactions) we analyzed a range of interaction intervals - from a few milliseconds to a minute. We used probability distributions to cluster the interactions according to their next inter-touch interval dynamics to discover systematic age-related changes at the distinct temporal clusters. There were age-related behavioral losses at the clusters occupying short intervals (~ 100 ms, R2 ~ 0.8) but gains at the long intervals (~ 4 s, R2 ~ 0.4). These correlates were independent of the years of experience on the phone or the choice of fingers used on the screen. We found further evidence for a compartmentalized influence of aging, as individuals simultaneously demonstrated both accelerated and decelerated aging at distant temporal clusters. In contrast to these strong correlations, cognitive tests probing sensorimotor, working memory, and executive processes revealed rather weak age-related decline. Contrary to the common notion of a simple behavioral decline with age based on conventional cognitive tests, we show that real-world behavior does not simply decline and the nature of aging systematically varies according to the underlying temporal dynamics. Of all the imaginable factors determining smartphone interactions in the real world, age-sensitive cognitive and behavioral processes can dominatingly dictate smartphone temporal dynamics.

Incorporating Ecological Momentary Assessment into multi-level investigations of adult development and aging: Promise and practical considerations

2020 ◽  
Author(s):  
Jennifer Lee Crawford ◽  
Tammy English ◽  
Todd Samuel Braver
Keyword(s):  
Adult Development ◽  
Ecological Momentary Assessment ◽  
Adult Life ◽  
Individual Variability ◽  
Aging Research ◽  
Adult Life Span ◽  
Age Related ◽  
Development And Aging ◽  
Ecological Momentary ◽  
Momentary Assessment

Ecological momentary assessment (EMA) represents a promising approach to study adult development and aging. In contrast to laboratory-based studies, EMA involves the repeated sampling of experiences in daily life contexts, enabling investigators to gain access to dynamic processes (e.g., situational contexts, intra-individual variability) that are likely to strongly contribute to age-related change across the adult life-span. As such, EMA approaches complement the prevailing research methods to study age differences (e.g., experimental paradigms, neuroimaging), and offer the potential to replicate and extend findings from the laboratory to more naturalistic contexts. Following an overview of the methodological and conceptual strengths of EMA approaches in adult development and aging research, we provide a guide for researchers interested in implementing EMA studies. Together, this work will highlight the tremendous potential in combining EMA methods with other laboratory-based approaches in order to increase the robustness, replicability, and real-world implications of research findings.

Age-Related Decline in Mentalizing Skills Across Adult Life Span

2009 ◽  
Vol 35 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Matteo Pardini ◽  
Paolo F. Nichelli
Keyword(s):  
Life Span ◽  
Adult Life ◽  
Adult Life Span ◽  
Age Related

Age-Related Cognitive Effects of Videogame Playing Across the Adult Life span

2017 ◽  
Vol 6 (4) ◽  
pp. 237-248 ◽  
Author(s):  
Ping Wang ◽  
Xing-Ting Zhu ◽  
Han-Hui Liu ◽  
Yi-Wen Zhang ◽  
Yang Hu ◽  
...  
Keyword(s):  
Life Span ◽  
Adult Life ◽  
Cognitive Effects ◽  
Adult Life Span ◽  
Age Related ◽  
Videogame Playing

scholarly journals A Conserved MTMR Lipid Phosphatase Increasingly Suppresses Autophagy in Brain Neurons During Aging

2021 ◽  
Author(s):  
Tibor Kovács ◽  
Janka Szinyákovics ◽  
Viktor Billes ◽  
Gábor Murányi ◽  
Virginia B. Varga ◽  
...  
Keyword(s):  
Brain Aging ◽  
Tyrosine Phosphatase ◽  
Adult Life ◽  
Fruit Fly ◽  
Cellular Damage ◽  
Adult Life Span ◽  
Brain Neurons ◽  
Lipid Phosphatase ◽  
Age Related ◽  
Cell Clearance

Abstract Aging is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown why autophagy becomes incapable of effectively eliminating harmful cellular materials at advanced ages. Here we show that age-associated defects in autophagic degradation occur at both early and late stages of the process. Furthermore, in the fruit fly Drosophila melanogaster, the myotubularin-related (MTMR) lipid phosphatase EDTP (egg-derived tyrosine phosphatase) known as an autophagy repressor gradually accumulates in brain neurons during the adult life span. The age-related increase in EDTP activity is associated with a growing DNA N6-adenine methylation at EDTP locus. MTMR14, the human counterpart of EDTP, also tends to accumulate with age in brain neurons. Thus, EDTP, and presumably MTMR14, promotes brain aging by increasingly suppressing autophagy throughout adulthood. We propose that EDTP and MTMR14 phosphatases operate as endogenous pro-aging factors setting the rate at which neurons age largely independently of environmental factors, and that autophagy is influenced by DNA N6-methyladenine levels.

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