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FoxO3 AND Aging

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https://www.readbyqxmd.com/read/28722347/foxo3-longevity-interactome-on-chromosome-6
#1
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Ayako Elliott, Bradley J Willcox
FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long-lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis-regulatory unit. The SNPs exhibited a high degree of LD in the Asian population, in which they define a specific longevity haplotype that is relatively common...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#2
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621049/lower-foxo3-mrna-expression-in-granulosa-cells-is-involved-in-unexplained-infertility
#3
Hikaru Yamamoto, Yoshiki Yamashita, Natsuho Saito, Atsushi Hayashi, Masami Hayashi, Yoshito Terai, Masahide Ohmichi
AIM: The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. METHODS: Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/μL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013...
June 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28615249/reduction-in-podocyte-sirt1-accelerates-kidney-injury-in-aging-mice
#4
Peter Y Chuang, Weijing Cai, Xuezhu Li, Lu Fang, Jin Xu, Rabi Yacoub, John Cijiang He, Kyung Lee
Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28430387/age-related-reduction-in-the-expression-of-foxo-transcription-factors-and-correlations-with-intervertebral-disc-degeneration
#5
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Koichi Masuda, Martin K Lotz
Aging is a main risk factor for intervertebral disc (IVD) degeneration, the main cause of low back pain. FOXO transcription factors are important regulators of tissue homeostasis and longevity. Here, we determined the expression pattern of FOXO in healthy and degenerated human IVD and the associations with IVD degeneration during mouse aging. FOXO expression was assessed by immunohistochemistry in normal and degenerated human IVD samples and in cervical and lumbar IVD from 6-, 12-, 24-, and 36-month-old C57BL/6J mice...
April 21, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28411009/skeletal-muscle-morphology-and-regulatory-signalling-in-endurance-trained-and-sedentary-individuals-the-influence-of-ageing
#6
U R Mikkelsen, J Agergaard, C Couppé, J F Grosset, A Karlsen, S P Magnusson, P Schjerling, M Kjaer, A L Mackey
Muscle mass in humans is inversely associated with circulating levels of inflammatory cytokines, but the interaction between ageing and training on muscle composition and the intra-muscular signalling behind inflammation and contractile protein synthesis and degradation is unknown. We studied 15 healthy life-long endurance runners, 12 age-matched untrained controls, 10 young trained and 12 young untrained individuals. Thigh muscle composition was investigated by magnetic resonance imaging (MRI), where non-contractile intramuscular tissue (NCIT) area (fat and connective tissue) was found to be greater in older but lower in trained individuals...
July 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28341621/cancer-cachexia-induced-muscle-atrophy-evidence-for-alterations-in-micrornas-important-for-muscle-size
#7
David Edward Lee, Jacob L Brown, Megan E Rosa-Caldwell, Thomas A Blackwell, Richard A Perry, Lemuel A Brown, Bhuwan Khatri, Dongwon Seo, Walter Gay Bottje, Tyrone Anthony Washington, Michael P Wiggs, Byung-Whi Kong, Nicholas Perry Greene
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy, however less is known specifically on miRNAs in cancer cachexia. PURPOSE: The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition...
March 24, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#8
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28241696/-changes-of-the-expression-for-genes-related-with-senescence-and-the-telomerase-activity-during-cellular-replicative-and-premature-senescence-in-human-embryonic-lung-fibroblasts
#9
J P Yang, W J Zhang, C X Jing, C P Wu, W D Ji, L Q Yang, Z X Zhuang
Objective: To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro. Methods: The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H(2)O(2)(premature senescence, PS)...
January 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28228489/age-dependent-shift-in-macrophage-polarisation-causes-inflammation-mediated-degeneration-of-enteric-nervous-system
#10
Laren Becker, Linh Nguyen, Jaspreet Gill, Subhash Kulkarni, Pankaj Jay Pasricha, Aida Habtezion
OBJECTIVE: The enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS...
February 21, 2017: Gut
https://www.readbyqxmd.com/read/28213398/foxo-integration-of-insulin-signaling-with-glucose-and-lipid-metabolism
#11
REVIEW
Sojin Lee, H Henry Dong
The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known as 'forkhead box' domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals...
May 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28206976/lipid-and-alzheimer-s-disease-genes-associated-with-healthy-aging-and-longevity-in-healthy-oldest-old
#12
Lauren C Tindale, Stephen Leach, John J Spinelli, Angela R Brooks-Wilson
Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202394/platelet-rich-plasma-prp-induces-chondroprotection-via-increasing-autophagy-anti-inflammatory-markers-and-decreasing-apoptosis-in-human-osteoarthritic-cartilage
#13
COMPARATIVE STUDY
Mayssam Moussa, Daniel Lajeunesse, George Hilal, Oula El Atat, Gaby Haykal, Rim Serhal, Antonio Chalhoub, Charbel Khalil, Nada Alaaeddine
OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28170423/nur77-deletion-impairs-muscle-growth-during-developmental-myogenesis-and-muscle-regeneration-in-mice
#14
Omar Cortez-Toledo, Caitlin Schnair, Peer Sangngern, Daniel Metzger, Lily C Chao
Muscle atrophy is a prevalent condition in illness and aging. Identifying novel pathways that control muscle mass may lead to therapeutic advancement. We previously identified Nur77 as a transcriptional regulator of glycolysis in skeletal muscle. More recently, we showed that Nur77 expression also controls myofiber size in mice. It was unknown, however, whether Nur77's regulation of muscle size begins during developmental myogenesis or only in adulthood. To determine the importance of Nur77 throughout muscle growth, we examined myofiber size at E18...
2017: PloS One
https://www.readbyqxmd.com/read/28118678/effect-of-sex-on-the-acute-skeletal-muscle-response-to-sprint-interval-exercise
#15
Lauren E Skelly, Jenna B Gillen, Martin J MacInnis, Brian J Martin, Adeel Safdar, Mahmood Akhtar, Maureen J MacDonald, Mark A Tarnopolsky, Martin J Gibala
What is the central question of this study? Are there sex-based differences in the acute skeletal muscle response to sprint interval training (SIT)? What is the main finding and its importance? In response to a SIT protocol that involved three 20 s bouts of 'all-out' cycling, the expression of multiple genes associated with mitochondrial biogenesis, metabolic control and structural remodelling was largely similar between men and women matched for fitness. Our findings cannot explain previous reports of sex-based differences in the adaptive response to SIT and suggest that the mechanistic basis for these differences remains to be elucidated...
January 24, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/27994057/foxo3-transcription-factor-is-essential-for-protecting-hematopoietic-stem-and-progenitor-cells-from-oxidative-dna-damage
#16
Carolina L Bigarella, Jianfeng Li, Pauline Rimmelé, Raymond Liang, Robert W Sobol, Saghi Ghaffari
Accumulation of damaged DNA in hematopoietic stem cells (HSC) is associated with chromosomal abnormalities, genomic instability, and HSC aging and might promote hematological malignancies with age. Despite this, the regulatory pathways implicated in the HSC DNA damage response have not been fully elucidated. One of the sources of DNA damage is reactive oxygen species (ROS) generated by both exogenous and endogenous insults. Balancing ROS levels in HSC requires FOXO3, which is an essential transcription factor for HSC maintenance implicated in HSC aging...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27976725/modulation-of-gut-microbiota-and-delayed-immunosenescence-as-a-result-of-syringaresinol-consumption-in-middle-aged-mice
#17
Si-Young Cho, Juewon Kim, Ji Hae Lee, Ji Hyun Sim, Dong-Hyun Cho, Il-Hong Bae, Hyunbok Lee, Min A Seol, Hyun Mu Shin, Tae-Joo Kim, Dae-Yong Kim, Su-Hyung Lee, Song Seok Shin, Sin-Hyeog Lm, Hang-Rae Kim
Age-associated immunological dysfunction (immunosenescence) is closely linked to perturbation of the gut microbiota. Here, we investigated whether syringaresinol (SYR), a polyphenolic lignan, modulates immune aging and the gut microbiota associated with this effect in middle-aged mice. Compared with age-matched control mice, SYR treatment delayed immunosenescence by enhancing the numbers of total CD3(+) T cells and naïve T cells. SYR treatment induced the expression of Bim as well as activation of FOXO3 in Foxp3(+) regulatory T cells (Tregs)...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936216/genetic-association-analysis-of-common-variants-in-foxo3-related-to-longevity-in-a-chinese-population
#18
Rong Lin, Yunxia Zhang, Dongjing Yan, Xiaoping Liao, Xianshou Wang, Yunxin Fu, Wangwei Cai
Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found...
2016: PloS One
https://www.readbyqxmd.com/read/27897419/exercise-restores-muscle-stem-cell-mobilization-regenerative-capacity-and-muscle-metabolic-alterations-via-adiponectin-adipor1-activation-in-samp10-mice
#19
Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya
BACKGROUND: Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions. METHODS: 25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months...
June 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27694344/longevity-associated-foxo3-genotype-and-its-impact-on-coronary-artery-disease-mortality-in-japanese-whites-and-blacks-a-prospective-study-of-three-american-populations
#20
Bradley J Willcox, Brian J Morris, Gregory J Tranah, Randi Chen, Kamal H Masaki, Qimei He, D Craig Willcox, Richard C Allsopp, Stefan Moisyadi, Mariana Gerschenson, Philip M C Davy, Leonard W Poon, Beatriz Rodriguez, Anne B Newman, Tamara B Harris, Steven R Cummings, Yongmei Liu, Neeta Parimi, Daniel S Evans, Timothy A Donlon
Background: We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail. Methods: We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study...
May 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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