scholarly journals Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology

2019 ◽  
Author(s):  
Mirre J P Simons ◽  
Laura Hartshorne ◽  
Suzan Trooster ◽  
Jessica Thomson ◽  
Marc Tatar
Keyword(s):  
Old Age ◽  
Large Scale ◽  
Meta Analysis ◽  
Demographic Data ◽  
Adult Life ◽  
Model Organisms ◽  
Pharmacological Treatments ◽  
Age Dependent ◽  
Early Adult Life ◽  
Mtor Signalling

AbstractResearch on the mechanisms of ageing has identified ways via which lifespan can be extended in model organisms, increasing the potential for translation of these findings to our own species. However, the large majority of research on animal models involves dietary, genetic or pharmacological treatments throughout life – limiting translational potential and ignoring age-dependent effects. Previously, we have suggested using demographic meta-analysis that reduced mTor signalling has the potential to instantly rejuvenate. We have now tested this prediction experimentally using large-scale demographic data (N > 10,000) combined with conditional knockdown of mTor in Drosophila melanogaster. Indeed, reduced mTor decreased mortality rate when applied during old age. Interestingly, we found that transient treatment during early adult life had long-lasting benefits. Age-dependent deep-RNAseq indicated that these effects arose from distinct physiology and implicate alternative splicing as a potential mechanism for the long-lasting benefits of transient mTor reduction. These findings suggest that reducing mTor short term or during old age could be used to combat ageing. In addition, our findings suggest that the results from experimental research on mTor signalling, and potentially other mechanisms of ageing, that employ life-long interventions are likely to be a complex composite of age-dependent effects that counteract or enhance each other.

scholarly journals OR28-01 Constitutive Activation of NRF2 Antioxidant Response Leads to Age-Dependent Goiter and Compensated Hypothyroidism in Male Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dionysios Chartoumpekis ◽  
Panos Ziros ◽  
Cédric Renaud ◽  
Massimo Bongiovanni ◽  
Ioannis Habeos ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Expression Profiles ◽  
Adult Life ◽  
Model Organisms ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Gene And Protein Expression ◽  
Age Dependent ◽  
Diffuse Goiter ◽  
Early Adult Life

Abstract Background: Familial non-toxic multinodular goiter (MNG) is a rare disease. KEAP1 gene (Kelch-like ECH-associated protein 1) that encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses, has been found to be one of the mutated genes that lead to familial MNG. The proposed association of KEAP1 with familial MNG is based on only two loss-of-function mutations in respective Japanese families, only one of which included proper phenotyping and demonstration of co-segregation of phenotype and mutation. To date, there is no experimental evidence from model organisms to support that decreased Keap1 levels can cause goiter. Hypothesis: We hypothesized that enhanced Nrf2 signaling induced by loss of Keap1 function in mice can lead to goiter. Methods: To this end, male Keap1 hypomorphic C57BL/6J mice that express ~80% less Keap1 in their tissues (Keap1 knockdown mice:“Keap1KD”) were studied at 3 and 12 months of age and compared to wild-type mice (WT). Plasma, thyroids and pituitary glands were collected for assessment of thyroid function by radioimmunoassays and for histology as well as gene and protein expression by quantitative PCR and immunoblotting respectively. Results: Keap1KD showed diffuse goiter that began to develop in early adult life and became highly prominent at the age of 12 months when the thyroids of Keap1KD were 6-fold heavier than WT. Histomorphometry assessment of thyroids showed that Keap1KD had ~3-fold larger follicle area and colloid compartment but no thyroid nodules or hyperplasia was detected. Keap1KD also showed primary hypothyroidism already in early adult life that was eventually well-compensated over time by increased TSH levels (at age of 12 months: WT TSH=47.7±9.1 mU/L, Keap1KD TSH=460±74 mU/L). This was also reflected in the pituitary gland of Keap1KD where Tshb mRNA was ~3-fold higher than WT. Despite a known stimulatory effect of Nrf2 on Tg gene transcription and Tg protein abundance, these measures were decreased in the thyroid of Keap1KD mice. No clear patterns were observed in the expression profiles of other thyroid hormone synthesis-specific factors, such as Duox1, Duoxa1, Duox2, Duoxa2, Tpo, Nis, Dio1, Dio2, Dehal1 mRNA levels, with the exception of Tg-processing and Tg-degrading cathepsins, including an increase in mature forms of cathepsins D, L and S. Conclusions: Keap1KD mice showed age-dependent diffuse goiter and compensated hypothyroidism. The precise mechanism accounting for the thyroidal phenotype remains to be elucidated, but it may involve enhanced Tg solubilization and excessive lysosomal Tg degradation. This study unravels novel roles of the druggable Keap1/Nrf2 pathway in thyroid function and economy. Subclinical hypothyroidism in Keap1KD mice may have broader implications regarding their use in metabolic research.

Ego Functioning in Old Age: Early Adult Life Antecedents

1974 ◽  
Vol 5 (2) ◽  
pp. 157-179 ◽  
Author(s):  
Joseph A. Kuypers
Keyword(s):  
Socioeconomic Status ◽  
Old Age ◽  
Young Adulthood ◽  
Family Relations ◽  
Adult Life ◽  
Early Adult Life ◽  
Intellectual Capacity ◽  
Alternative Measures ◽  
The Subject ◽  
And Behavior

Do aspects of intelligence, health, socioeconomic status, personality, and family relations in young adulthood relate to adaptability in old age? Correlations are reported between three alternative measures of old age adaptability (coping, defense, and disorganization) and measures in five areas of status and behavior in young adulthood (representing a 40 year longitudinal analysis). Coping ability in old age is most associated with variations in intellectual capacity and socioeconomic status, especially for women. Ego disorganization in old age is most related to variations in socioeconomic status and family relations in young adulthood. The data suggest that adaptability in old age is associated with environments and behaviors early along the adult life course but that the strength of over-time connection varies according to the sex of the subject, the model of old age adaptability used, and the aspects of status and behavior considered in young adulthood.

Relationship between total plasma homocysteine and the risk of aneurysms – a meta-analysis

VASA ◽  
2020 ◽  
pp. 1-6
Author(s):  
Hanji Zhang ◽  
Dexin Yin ◽  
Yue Zhao ◽  
Yezhou Li ◽  
Dejiang Yao ◽  
...  
Keyword(s):  
Large Scale ◽  
Meta Analysis ◽  
Single Species ◽  
Total Plasma ◽  
Control Groups ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
The Difference ◽  
The Relationship ◽  
Healthy Participants

Summary: Our meta-analysis focused on the relationship between homocysteine (Hcy) level and the incidence of aneurysms and looked at the relationship between smoking, hypertension and aneurysms. A systematic literature search of Pubmed, Web of Science, and Embase databases (up to March 31, 2020) resulted in the identification of 19 studies, including 2,629 aneurysm patients and 6,497 healthy participants. Combined analysis of the included studies showed that number of smoking, hypertension and hyperhomocysteinemia (HHcy) in aneurysm patients was higher than that in the control groups, and the total plasma Hcy level in aneurysm patients was also higher. These findings suggest that smoking, hypertension and HHcy may be risk factors for the development and progression of aneurysms. Although the heterogeneity of meta-analysis was significant, it was found that the heterogeneity might come from the difference between race and disease species through subgroup analysis. Large-scale randomized controlled studies of single species and single disease species are needed in the future to supplement the accuracy of the results.

Memory for faces in old age: A meta-analysis.

2018 ◽  
Vol 33 (6) ◽  
pp. 904-923 ◽  
Author(s):  
Natalie Martschuk ◽  
Siegfried L. Sporer
Keyword(s):  
Old Age ◽  
Meta Analysis

Identification of and Correction for Publication Bias: Comment

2019 ◽  
Author(s):  
Amanda Kvarven ◽  
Eirik Strømland ◽  
Magnus Johannesson
Keyword(s):  
Publication Bias ◽  
False Positive ◽  
Large Scale ◽  
Meta Analysis ◽  
False Positive Rate ◽  
Effect Sizes ◽  
Replication Studies ◽  
Moderate Reduction ◽  
Positive Rate ◽  
Meta Analyses

Andrews & Kasy (2019) propose an approach for adjusting effect sizes in meta-analysis for publication bias. We use the Andrews-Kasy estimator to adjust the result of 15 meta-analyses and compare the adjusted results to 15 large-scale multiple labs replication studies estimating the same effects. The pre-registered replications provide precisely estimated effect sizes, which do not suffer from publication bias. The Andrews-Kasy approach leads to a moderate reduction of the inflated effect sizes in the meta-analyses. However, the approach still overestimates effect sizes by a factor of about two or more and has an estimated false positive rate of between 57% and 100%.

Temporal Discounting Across Adulthood: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Kendra Leigh Seaman ◽  
Sade J Abiodun ◽  
Zöe Fenn ◽  
Gregory Russell Samanez-Larkin ◽  
Rui Mata
Keyword(s):  
Age Differences ◽  
Intertemporal Choice ◽  
Meta Analysis ◽  
Empirical Work ◽  
Adult Life ◽  
Temporal Discounting ◽  
Total N ◽  
Adult Age ◽  
Adult Age Differences ◽  
Choice Tasks

A number of developmental theories have been proposed that make differential predictions about the links between age and temporal discounting; that is, the valuation of rewards at different points in time. Most empirical studies examining adult age differences in temporal discounting have relied on economic intertemporal choice tasks, which pit choosing a smaller, sooner monetary reward against choosing a larger, later one. Although initial studies using these tasks suggested older adults discount less than younger adults, follow-up studies provided heterogeneous, and thus inconclusive, results. Using an open science approach, we test the replicability of adult age differences in temporal discounting by conducting a preregistered systematic literature search and meta-analysis of adult age differences in intertemporal choice tasks. Across 37 cross-sectional studies (Total N = 104,736), we found no reliable relation between age and temporal discounting (r = -0.081, 95% CI [-0.185, 0.025]). We also found little evidence of publication bias or p-hacking. Exploratory analyses of moderators found no effect of experimental design (e.g., extreme-group vs. continuous age), incentives (hypothetical vs. rewards), amount of delay (e.g., days, weeks, months, or years), or quantification of discounting behavior (e.g., proportion of immediate choices vs. parameters from computational modeling). Additional analyses of 12 participant-level data sets found little support for a nonlinear relation between age and temporal discounting across adulthood. Overall, the results suggest that adult age is not reliably associated with individual differences in temporal discounting. We provide recommendations for future empirical work on temporal discounting across the adult life span.

Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis

2020 ◽  
Vol 17 (2) ◽  
pp. 105-111
Author(s):  
Haitao Liu ◽  
Wei Ge ◽  
Wei Chen ◽  
Xue Kong ◽  
Weiming Jian ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Large Scale ◽  
Late Onset ◽  
Meta Analysis ◽  
Case Control ◽  
Cochrane Library ◽  
Positive Trend ◽  
Case Control Studies ◽  
China National Knowledge Infrastructure ◽  
Aldh2 Gene

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.

Serum Copper Level and Polycystic Ovarian Syndrome: A Meta-Analysis

2021 ◽  
pp. 1-8
Author(s):  
Qingtao Jiang ◽  
Feng Zhang ◽  
Lei Han ◽  
Baoli Zhu ◽  
Xin Liu
Keyword(s):  
Large Scale ◽  
Polycystic Ovarian Syndrome ◽  
Meta Analysis ◽  
Serum Copper ◽  
Copper Level ◽  
Serum Copper Level ◽  
Copper Status ◽  
Plasma Copper ◽  
Mean Differences ◽  
Ovarian Syndrome

<b><i>Introduction:</i></b> The association of serum copper with polycystic ovarian syndrome (PCOS) has been studied for years, but no definite conclusion is drawn. Therefore, we conducted a meta-analysis to investigate serum copper concentrations in PCOS subjects compared with healthy controls. <b><i>Methods:</i></b> Electronic search was performed in PubMed, Google Scholar, and Scopus up to June 30, 2020, without any restriction. Standardized mean differences (SMDs) with corresponding 95% CIs in serum copper levels were employed with random-effects model. <i>I</i><sup>2</sup> was applied to evaluate heterogeneity among studies. <b><i>Results:</i></b> Nine studies, measuring plasma copper levels in 1,168 PCOS patients and 1,106 controls, were included. Pooled effect size suggested serum copper level was significantly higher in women with PCOS (SMD = 0.51 μg/mL, 95% CI = [0.30, 0.72], <i>p</i> &#x3c; 0.0001). The overall heterogeneity was not connected with subgroups of the country, but derived from the opposite result of 1 study. <b><i>Conclusion:</i></b> Our research generally indicated circulating copper level in PCOS sufferers was significantly higher than normal controls. Large-scale studies are still needed to elucidate the clear relation between copper status and etiology of PCOS.

Pharmacological Treatments of Bell's Palsy in Adults: A Systematic Review and Network Meta‐Analysis

2021 ◽  
Author(s):  
Mir Mohammad Jalali ◽  
Robabeh Soleimani ◽  
Soheil Soltanipour ◽  
Seyede Melika Jalali
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Bell’S Palsy ◽  
Pharmacological Treatments ◽  
Bell's Palsy
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