scholarly journals Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort

2016 ◽  
Author(s):  
Ana Viñuela ◽  
Andrew A Brown ◽  
Alfonso Buil ◽  
Pei-Chien Tsai ◽  
Matthew N Davies ◽  
...  

AbstractGene expression changes with age have consequences for healthy aging and disease development. Here we investigate age-related changes in gene expression measured by RNA-seq in four tissues and the interplay between genotypes and age-related changes in expression. Using concurrently measured methylation array data from fat we also investigate the relationship between methylation, gene expression and age. We identified age-dependent changes in mean levels of gene expression in 5,631 genes and in splicing of 904 genes. Age related changes were widely shared across tissues, with up to 60% of age-related changes in expression and 47% on splicing in multi-exonic genes shared; amongst these we highlight effects on genes involved in diseases such as Alzheimer and cancer. We identified 137 genes with age-related changes in variance and 42 genes with age-dependent discordance between genetically identical individuals; implying the latter are driven by environmental effects. We also give four examples where genetic control of expression is affected by the aging process. Analysis of methylation observed a widespread and stronger effect of age on methylation than expression; however we did not find a strong relationship between age-related changes in both expression and methylation. In summary, we quantified aging affects in splicing, level and variance of gene expression, and show that these processes can be both environmentally and genetically influenced.

Gerontology ◽  
2015 ◽  
Vol 62 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Agata Wronska ◽  
Aleksandra Lawniczak ◽  
Piotr M. Wierzbicki ◽  
Zbigniew Kmiec

Background: Sirtuins (SIRT1-7) have been implicated to mediate the beneficial effects of calorie restriction for healthy aging. While the physiological functions of SIRT7 are still poorly understood, SIRT7 has recently been shown to affect ribosome biogenesis, mitochondrial gene expression, and hepatic lipid metabolism. Objective: To analyze the effects of age and short-term calorie restriction (SCR) and subsequent refeeding on SIRT7 expression in key metabolic tissues. Methods: Four- and 24-month-old male Wistar rats were subjected to 40% SCR for 30 days, followed by ad libitum feeding for 2 or 4 days. Liver, white adipose tissue (WAT), heart and skeletal muscle samples were analyzed by real-time PCR and Western blotting for SIRT7 mRNA and protein expression, respectively. Results: Aging had diverse effects on SIRT7 levels in lipogenic tissues: both the mRNA and protein levels increased in the retroperitoneal depot (rWAT), did not change in the epididymal depot (eWAT), and decreased in the subcutaneous depot (sWAT) and the liver of old as compared to young animals. In the heart, extensor digitorum longus muscle (EDL) and soleus muscle (SOL), Sirt7 gene but not protein expression was lower in old than in young control rats. SCR did not affect SIRT7 expression in WAT and the liver in both age groups. In the heart of young animals, SCR did not affect SIRT7 mRNA or protein level. In EDL, SIRT7 protein but not mRNA levels decreased after SCR and remained reduced upon refeeding. In SOL, both SIRT7 mRNA and protein expression were inhibited by refeeding. In old rats, cardiac Sirt7 expression increased after SCR and refeeding. In old rats' EDL and SOL muscles, SIRT7 protein expression was inhibited by refeeding. Conclusion: Age-related changes of SIRT7 gene expression in key organs of energy homeostasis are tissue dependent.


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jason B Wheeler ◽  
Robert E Stroud ◽  
Elizabeth K Nadeau ◽  
Rupak Mukherjee ◽  
John S Ikonomidis ◽  
...  

Background: Age-related changes in the thoracic aorta, including alterations in medial extracellular matrix (ECM) in terms of increased collagen and reduced medial cellularity, are associated with a loss of contractility in isolated smooth muscle cells (SMCs). SMCs can regulate both the passive ECM content and mechanical properties of the aorta. However, the age-dependent effects on cellular proliferation, migration, adhesion, and gene expression (phenotype) of aortic SMCs remains unknown. Accordingly, the goal of this study was to determine the age-dependent changes in these characteristics of aortic SMCs. Methods/Results: Primary cultures of SMCs were established from thoracic aortic explants harvested from 6 month (n=6) and 21 month old (n=6) C57BL/6 mice. Cellular proliferation (by Cyquant assay), migration (Boyden chamber), and adhesion (on a cell culture treated surface) were reduced in the SMCs from old mice compared to those from young mice. Expression of ECM remodeling genes, including ECM proteins, matrix metalloproteinases, and tissue inhibitors of MMPs, produced a distinct genotypic profile between old and young SMCs (Figure). Conclusions: Findings from this study demonstrated that thoracic aortic SMCs from old mice are phenotypically distinct compared to those from young mice. Further, the changes in gene expression with age are consistent with the ECM changes observed in the aorta. Future studies will be required to define the role of these age-related changes in aortic SMC phenotype in aortopathies.


2021 ◽  
pp. 1-17
Author(s):  
Anna A. Matejko ◽  
Daniel Ansari

Abstract Visuospatial working memory (VSWM) plays an important role in arithmetic problem solving, and the relationship between these two skills is thought to change over development. Even though neuroimaging studies have demonstrated that VSWM and arithmetic both recruit frontoparietal networks, inferences about common neural substrates have largely been made by comparisons across studies. Little work has examined how brain activation for VSWM and arithmetic converge within the same participants and whether there are age-related changes in the overlap of these neural networks. In this study, we examined how brain activity for VSWM and arithmetic overlap in 38 children and 26 adults. Although both children and adults recruited the intraparietal sulcus (IPS) for VSWM and arithmetic, children showed more focal activation within the right IPS, whereas adults recruited the bilateral IPS, superior frontal sulcus/middle frontal gyrus, and right insula. A comparison of the two groups revealed that adults recruited a more left-lateralized network of frontoparietal regions for VSWM and arithmetic compared with children. Together, these findings suggest possible neurocognitive mechanisms underlying the strong relationship between VSWM and arithmetic and provide evidence that the association between VSWM and arithmetic networks changes with age.


2016 ◽  
Vol 6 (1-2) ◽  
pp. 119-146 ◽  
Author(s):  
Henrike K. Blumenfeld ◽  
Scott R. Schroeder ◽  
Susan C. Bobb ◽  
Max R. Freeman ◽  
Viorica Marian

Abstract Recent research suggests that bilingual experience reconfigures linguistic and nonlinguistic cognitive processes. We examined the relationship between linguistic competition resolution and nonlinguistic cognitive control in younger and older adults who were either bilingual or monolingual. Participants heard words in English and identified the referent among four pictures while eye-movements were recorded. Target pictures (e.g., cab) appeared with a phonological competitor picture (e.g., cat) and two filler pictures. After each eye-tracking trial, priming probes assessed residual activation and inhibition of target and competitor words. When accounting for processing speed, results revealed that age-related changes in activation and inhibition are smaller in bilinguals than in monolinguals. Moreover, younger and older bilinguals, but not monolinguals, recruited similar inhibition mechanisms during word identification and during a nonlinguistic Stroop task. Results suggest that, during lexical access, bilinguals show more consistent competition resolution and recruitment of cognitive control across the lifespan than monolinguals.


Metabolism ◽  
1995 ◽  
Vol 44 (3) ◽  
pp. 320-324 ◽  
Author(s):  
Stephen J. Giddings ◽  
Lynn R. Carnaghi ◽  
Arshag D. Mooradian

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ian R Lanza ◽  
Daniel K Short ◽  
Kevin R Short ◽  
Yan W Asmann ◽  
Sreekumar Raghavakaimal ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2601
Author(s):  
Tanja Grubić Kezele ◽  
Božena Ćurko-Cofek

Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.


1983 ◽  
Vol 29 (1) ◽  
pp. 74-79 ◽  
Author(s):  
T J Wilke

Abstract The thyroid hormone/thyroxin-binding globulin (TBG) ratio and the free thyroid hormone index (FTI) were compared in 372 subjects classified according to age, sex, and biochemical and clinical findings. Age-related variations in thyroid function tests were investigated, as was the relationship between triiodothyronine uptake and TBG. Men, but not women, showed significant age-dependent changes in concentrations of thyroid hormones. FTI was as good as the thyroid hormone/TBG ratio in hyperthyroidism and was a better index of thyroid status in pregnancy, TBG deficiency, and hypothyroidism. In addition, the triiodothyronine uptake correlated extremely well with TBG (r = -0.95, p less than 0.001) and was very efficient in detecting decreased and significantly increased concentrations of TBG. I conclude that FTI is a better discriminator of functional status of the thyroid over a wider range of TBG values than is the thyroid hormone/TBG ratio. Further, the triiodothyronine uptake test produced diagnostic information equivalent to that of TBG estimation and thus should not be replaced in routine use.


Sign in / Sign up

Export Citation Format

Share Document