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FoxO3 AND Aging

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https://www.readbyqxmd.com/read/29080996/impact-of-local-heating-and-cooling-on-skeletal-muscle-transcriptional-response-related-to-myogenesis-and-proteolysis
#1
Roksana B Zak, B M Hassenstab, L K Zuehlke, M W S Heesch, R J Shute, T L Laursen, D T LaSalle, D R Slivka
PURPOSE: To determine the impact of local muscle heating and cooling on myogenic and proteolytic gene responses following resistance exercise. METHODS: Recreationally trained males (n = 12), age 25.3 ± 1.5, % body fat 13.6 ± 1.92, completed four sets of 8-12 repetitions of unilateral leg press and leg extension while heating one leg, and cooling the other. Muscle biopsies were taken from the vastus lateralis of each leg pre and 4 h post exercise. RESULTS: MyoD, FOXO1, and MuRF1 mRNA increased with exercise regardless of temperature (p < 0...
October 28, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28977569/effects-of-foxo3-polymorphisms-on-survival-to-extreme-longevity-in-four-centenarian-studies
#2
Harold Bae, Anastasia Gurinovich, Alberto Malovini, Gil Atzmon, Stacy L Andersen, Francesco Villa, Nir Barzilai, Annibale Puca, Thomas T Perls, Paola Sebastiani
Previous studies note specific FOXO3 single-nucleotide polymorphisms (SNPs) associated with human longevity. However, it is not clear if these SNPs influence mortality risk beyond the oldest 1 percentile of survival. Using data from four longevity studies (total n = 8,266, age range 96-119 years for cases), we tested gene-wide association between 107 SNPs and survival to at least the oldest 1 percentile of survival for the 1900 birth cohort (≥96, white males; ≥100 white females). This analysis replicated 17 previously published variants, several of which are significant expression quantitative trait loci of FOXO3; rs6911407 and rs2253310 have the most significant effect on FOXO3 expressions in brain tissue...
July 18, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28894507/foxo-transcriptional-factors-and-long-term-living
#3
REVIEW
Ghulam Murtaza, Abida Kalsoom Khan, Rehana Rashid, Saiqa Muneer, Syed Muhammad Farid Hasan, Jianxin Chen
Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28782600/mir-18a-induces-myotubes-atrophy-by-down-regulating-igfi
#4
Chuncheng Liu, Meng Wang, Min Chen, Kuo Zhang, Lijie Gu, Qiuyan Li, Zhengquan Yu, Ning Li, Qingyong Meng
Muscle atrophy occurs when there is a net loss of muscle mass, leading to a change in the balance between protein synthesis and protein degradation. Igf1 is important for protein synthesis in muscle cells and can induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy via the PI3K/Akt pathway in mice, consequently restoring and improving muscle mass and strength. In this study, we show that miR-18a expression is down-regulated during C2C12 myoblast differentiation and mouse tibialis anterior muscle postnatal development...
September 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#5
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
August 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28722347/foxo3-longevity-interactome-on-chromosome-6
#6
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...
October 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
#7
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
#8
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
#9
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...
September 1, 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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