journal
MENU ▼
Read by QxMD icon Read
search

Aging Cell

journal
https://www.readbyqxmd.com/read/29774655/ctc1-stn1-coordinates-g-and-c-strand-synthesis-to-regulate-telomere-length
#1
Peili Gu, Shuting Jia, Taylor Takasugi, Eric Smith, Jayakrishnan Nandakumar, Eric Hendrickson, Sandy Chang
Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#2
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29766639/oxidation-resistance-1-is-a-novel-senolytic-target
#3
Xin Zhang, Suping Zhang, Xingui Liu, Yingying Wang, Jianhui Chang, Xuan Zhang, Samuel G Mackintosh, Alan J Tackett, Yonghan He, Dongwen Lv, Remi-Martin Laberge, Judith Campisi, Jianrong Wang, Guangrong Zheng, Daohong Zhou
The selective depletion of senescent cells (SCs) by small molecules, termed senolytic agents, is a promising therapeutic approach for treating age-related diseases and chemotherapy- and radiotherapy-induced side effects. Piperlongumine (PL) was recently identified as a novel senolytic agent. However, its mechanism of action and molecular targets in SCs was unknown and thus was investigated. Specifically, we used a PL-based chemical probe to pull-down PL-binding proteins from live cells and then mass spectrometry-based proteomic analysis to identify potential molecular targets of PL in SCs...
May 15, 2018: Aging Cell
https://www.readbyqxmd.com/read/29749694/trimethylamine-n-oxide-promotes-brain-aging-and-cognitive-impairment-in-mice
#4
Dang Li, Yilang Ke, Rui Zhan, Changjie Liu, Mingming Zhao, Aiping Zeng, Xiaoyun Shi, Liang Ji, Si Cheng, Bing Pan, Lemin Zheng, Huashan Hong
Gut microbiota can influence the aging process and may modulate aging-related changes in cognitive function. Trimethylamine-N-oxide (TMAO), a metabolite of intestinal flora, has been shown to be closely associated with cardiovascular disease and other diseases. However, the relationship between TMAO and aging, especially brain aging, has not been fully elucidated. To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24-week-old senescence-accelerated prone mouse strain 8 (SAMP8) and age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice for 16 weeks...
May 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29749079/acute-tau-knockdown-in-the-hippocampus-of-adult-mice-causes-learning-and-memory-deficits
#5
Ramon Velazquez, Eric Ferreira, An Tran, Emily C Turner, Ramona Belfiore, Caterina Branca, Salvatore Oddo
Misfolded and hyperphosphorylated tau accumulates in several neurodegenerative disorders including Alzheimer's disease, frontotemporal dementia with Parkinsonism, corticobasal degeneration, progressive supranuclear palsy, Down syndrome, and Pick's disease. Tau is a microtubule-binding protein, and its role in microtubule stabilization is well defined. In contrast, while growing evidence suggests that tau is also involved in synaptic physiology, a complete assessment of tau function in the adult brain has been hampered by robust developmental compensation of other microtubule-binding proteins in tau knockout mice...
May 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29745022/restoring-mitochondrial-dna-copy-number-preserves-mitochondrial-function-and-delays-vascular-aging-in-mice
#6
Kirsty Foote, Johannes Reinhold, Emma P K Yu, Nichola L Figg, Alison Finigan, Michael P Murphy, Martin R Bennett
Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging...
May 9, 2018: Aging Cell
https://www.readbyqxmd.com/read/29744983/expression-of-p16-ink-4a-is-a-biomarker-of-chondrocyte-aging-but-does-not-cause-osteoarthritis
#7
Brian O Diekman, Garrett A Sessions, John A Collins, Anne K Knecht, Susan L Strum, Natalia K Mitin, Cathy S Carlson, Richard F Loeser, Norman E Sharpless
Cellular senescence drives a functional decline of numerous tissues with aging by limiting regenerative proliferation and/or by producing pro-inflammatory molecules known as the senescence-associated secretory phenotype (SASP). The senescence biomarker p16INK 4a is a potent inhibitor of the cell cycle but is not essential for SASP production. Thus, it is unclear whether p16INK 4a identifies senescence in hyporeplicative cells such as articular chondrocytes and whether p16INK 4a contributes to pathologic characteristics of cartilage aging...
May 9, 2018: Aging Cell
https://www.readbyqxmd.com/read/29740932/antagonizing-peroxisome-proliferator-activated-receptor-%C3%AE-facilitates-m1-to-m2-shift-of-microglia-by-enhancing-autophagy-via-the-lkb1-ampk-signaling-pathway
#8
Juan Ji, Teng-Fei Xue, Xu-Dong Guo, Jin Yang, Ruo-Bing Guo, Juan Wang, Ji-Ye Huang, Xiao-Jie Zhao, Xiu-Lan Sun
Microglia-mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing evidence that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)-induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS-stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL-4, IGF-1, TGF-β1, TGF-β2, TGF-β3, G-CSF, and GM-CSF, and reduced the expression of M1 markers, such as CD86, Cox-2, iNOS, IL-1β, IL-6, TNF-α, IFN-γ, and CCL2, thereby inhibiting NFκB-IKKβ activation...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#9
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29730901/htra1-an-age-related-macular-degeneration-protease-processes-extracellular-matrix-proteins-efemp1-and-tsp1
#10
Michael K Lin, Jin Yang, Chun Wei Hsu, Anuradha Gore, Alexander G Bassuk, Lewis M Brown, Ryan Colligan, Jesse D Sengillo, Vinit B Mahajan, Stephen H Tsang
High-temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age-related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key...
May 5, 2018: Aging Cell
https://www.readbyqxmd.com/read/29706024/overexpression-of-cyb5r3-and-nqo1-two-nad-producing-enzymes-mimics-aspects-of-caloric-restriction
#11
Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A Aon, Kenneth W Fishbein, Kevin J Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael de Cabo
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases...
April 28, 2018: Aging Cell
https://www.readbyqxmd.com/read/29696791/lifelong-reduction-in-complex-iv-induces-tissue-specific-metabolic-effects-but-does-not-reduce-lifespan-or-healthspan-in-mice
#12
Sathyaseelan S Deepa, Gavin Pharaoh, Michael Kinter, Vivian Diaz, Wilson C Fok, Kaitlyn Riddle, Daniel Pulliam, Shauna Hill, Kathleen E Fischer, Vanessa Soto, Constantin Georgescu, Jonathan D Wren, Carlo Viscomi, Arlan Richardson, Holly Van Remmen
Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1-/- mice. The lack of deleterious phenotypes in Surf1-/- mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1-/- vs...
April 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29696779/necroptosis-increases-with-age-and-is-reduced-by-dietary-restriction
#13
Sathyaseelan S Deepa, Archana Unnikrishnan, Stephanie Matyi, Niran Hadad, Arlan Richardson
Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7- and 1.9-fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P-MLKL and P-RIPK3 to levels similar to adult mice...
April 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29696758/micrornas-in-hereditary-and-sporadic-premature-aging-syndromes-and-other-laminopathies
#14
REVIEW
Diane Frankel, Valérie Delecourt, Karim Harhouri, Annachiara De Sandre-Giovannoli, Nicolas Lévy, Elise Kaspi, Patrice Roll
Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue-specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson-Gilford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation...
April 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29671950/comparative-transcriptomics-across-14-drosophila-species-reveals-signatures-of-longevity
#15
Siming Ma, Andrei S Avanesov, Emily Porter, Byung Cheon Lee, Marco Mariotti, Nadezhda Zemskaya, Roderic Guigo, Alexey A Moskalev, Vadim N Gladyshev
Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer-lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing...
April 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29659168/metformin-alleviates-human-cellular-aging-by-upregulating-the-endoplasmic-reticulum-glutathione-peroxidase-7
#16
Jingqi Fang, Jiping Yang, Xun Wu, Gangming Zhang, Tao Li, Xi'e Wang, Hong Zhang, Chih-Chen Wang, Guang-Hui Liu, Lei Wang
Metformin, an FDA-approved antidiabetic drug, has been shown to elongate lifespan in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low-dose metformin treatment extends the lifespan of human diploid fibroblasts and mesenchymal stem cells. We report that a low dose of metformin upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7). GP×7 expression levels are decreased in senescent human cells, and GPx7 depletion results in premature cellular senescence...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29659128/activation-of-dna-demethylases-attenuates-aging-associated-arterial-stiffening-and-hypertension
#17
Kai Chen, Zhongjie Sun
DNA methylation increases with age. The objective of this study was to investigate whether compound H, a potential activator of DNA demethylases, attenuates aging-related arterial stiffness and hypertension. Aged mice (24-27 months) and adult mice (12 months) were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in aged mice. Notably, daily treatments with compound H (15 mg/kg, IP) for 2 weeks significantly attenuated the aging-related increases in PWV and BP...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29659123/advanced-oxidation-protein-products-induce-pre-osteoblast-apoptosis-through-a-nicotinamide-adenine-dinucleotide-phosphate-oxidase-dependent-mitogen-activated-protein-kinases-mediated-intrinsic-apoptosis-pathway
#18
Si-Yuan Zhu, Jing-Shen Zhuang, Qian Wu, Zhong-Yuan Liu, Cong-Rui Liao, Shi-Gan Luo, Jian-Ting Chen, Zhao-Ming Zhong
Osteoblast apoptosis contributes to age-related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age-related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3-E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#19
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29654651/enhanced-longevity-and-metabolism-by-brown-adipose-tissue-with-disruption-of-the-regulator-of-g-protein-signaling-14
#20
Dorothy E Vatner, Jie Zhang, Marko Oydanich, John Guers, Elena Katsyuba, Lin Yan, David Sinclair, Johan Auwerx, Stephen F Vatner
Disruption of the regulator for G protein signaling 14 (RGS14) knockout (KO) in mice extends their lifespan and has multiple beneficial effects related to healthful aging, that is, protection from obesity, as reflected by reduced white adipose tissue, protection against cold exposure, and improved metabolism. The observed beneficial effects were mediated by improved mitochondrial function. But most importantly, the main mechanism responsible for the salutary properties of the RGS14 KO involved an increase in brown adipose tissue (BAT), which was confirmed by surgical BAT removal and transplantation to wild-type (WT) mice, a surgical simulation of a molecular knockout...
April 14, 2018: Aging Cell
journal
journal
39893
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"