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FoxO3 AND Aging

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https://www.readbyqxmd.com/read/29733381/the-longevity-snp-rs2802292-uncovered-hsf1-activates-stress-dependent-expression-of-foxo3-through-an-intronic-enhancer
#1
Valentina Grossi, Giovanna Forte, Paola Sanese, Alessia Peserico, Tugsan Tezil, Martina Lepore Signorile, Candida Fasano, Rosaura Lovaglio, Rosanna Bagnulo, Daria C Loconte, Francesco C Susca, Nicoletta Resta, Cristiano Simone
The HSF and FOXO families of transcription factors play evolutionarily conserved roles in stress resistance and lifespan. In humans, the rs2802292 G-allele at FOXO3 locus has been associated with longevity in all human populations tested; moreover, its copy number correlated with reduced frequency of age-related diseases in centenarians. At the molecular level, the intronic rs2802292 G-allele correlated with increased expression of FOXO3, suggesting that FOXO3 intron 2 may represent a regulatory region. Here we show that the 90-bp sequence around the intronic single nucleotide polymorphism rs2802292 has enhancer functions, and that the rs2802292 G-allele creates a novel HSE binding site for HSF1, which induces FOXO3 expression in response to diverse stress stimuli...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29717119/dkk3-dependent-transcriptional-regulation-controls-age-related-skeletal-muscle-atrophy
#2
Jie Yin, Lele Yang, Yangli Xie, Yan Liu, Sheng Li, Wenjun Yang, Bo Xu, Hongbin Ji, Lianghua Ding, Kun Wang, Gang Li, Lin Chen, Ping Hu
Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63, driving muscle atrophy...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691711/biomechanics-and-mechanical-signaling-in-the-ovary-a-systematic-review
#3
REVIEW
Jaimin S Shah, Reem Sabouni, Kamaria C Cayton Vaught, Carter M Owen, David F Albertini, James H Segars
PURPOSE: Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis...
April 24, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29688278/minimal-shortening-of-leukocyte-telomere-length-across-age-groups-in-a-cross-sectional-study-for-carriers-of-a-longevity-associated-foxo3-allele
#4
Philip M C Davy, D Craig Willcox, Michio Shimabukuro, Timothy A Donlon, Trevor Torigoe, Makoto Suzuki, Moritake Higa, Hiroaki Masuzaki, Masataka Sata, Randi Chen, Rachel Murkofsky, Brian J Morris, Eunjung Lim, Richard C Allsopp, Bradley J Willcox
FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprising of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50) participants...
April 21, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29627834/effects-of-long-non-coding-rna-linc00963-on-renal-interstitial-fibrosis-and-oxidative-stress-of-rats-with-chronic-renal-failure-via-the-foxo-signaling-pathway
#5
Wen Chen, Lei Zhang, Zhong-Qi Zhou, Yue-Qin Ren, Li-Na Sun, Yu-Lin Man, Zhong-Wei Ma, Zhi-Kui Wang
BACKGROUND/AIMS: Chronic renal failure (CRF) is usually associated with chronic diseases such as congestive heart failure and diabetes mellitus, the prevalence of which is increased with age. This study is designed to investigate the role of long intergenic non-coding RNA (lincRNA) LINC00963 in renal interstitial fibrosis (RIF) and oxidative stress (OS) of CRF via the forkhead box O (FoxO) signaling pathway. METHODS: Microarray data and annotated probe files related to CRF were downloaded by retrieving Gene Expression Omnibus (GEO) database to screen differentially expressed lncRNA...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29444976/foxo-transcription-factors-modulate-autophagy-and-proteoglycan-4-in-cartilage-homeostasis-and-osteoarthritis
#6
Tokio Matsuzaki, Oscar Alvarez-Garcia, Sho Mokuda, Keita Nagira, Merissa Olmer, Ramya Gamini, Kohei Miyata, Yukio Akasaki, Andrew I Su, Hiroshi Asahara, Martin K Lotz
Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors protect against cellular and organismal aging, and FoxO expression in cartilage is reduced with aging and in OA. To investigate the role of FoxO in cartilage, Col2Cre-FoxO1, 3, and 4 single knockout (KO) and triple KO mice (Col2Cre-TKO) were analyzed. Articular cartilage in Col2Cre-TKO and Col2Cre-FoxO1 KO mice was thicker than in control mice at 1 or 2 months of age. This was associated with increased proliferation of chondrocytes of Col2Cre-TKO mice in vivo and in vitro...
February 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29433738/foxo3-and-exceptional-longevity-insights-from-hydra-to-humans
#7
Philip M C Davy, Richard C Allsopp, Timothy A Donlon, Brian J Morris, Donald Craig Willcox, Bradley J Willcox
Aging is a complex, multifactorial process with significant plasticity. While several biological pathways appear to influence aging, few genes have been identified that are both evolutionarily conserved and have a strong impact on aging and age-related phenotypes. The FoxO3 gene (FOXO3), and its homologs in model organisms, appears especially important, forming a key gene in the insulin/insulin-like growth factor-signaling pathway, and influencing life span across diverse species. We highlight some of the key findings that are associated with FoxO3 protein, its gene and homologs in relation to lifespan in different species, and the insights these findings might provide about the molecular, cellular, and physiological processes that modulate aging and longevity in humans...
2018: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/29433734/foxo-in-neural-cells-and-diseases-of-the-nervous-system
#8
Evan E Santo, Jihye Paik
The evolutionarily conserved FOXO family of transcription factors has emerged as a significant arbiter of neural cell fate and function in mammals. From the neural stem cell (NSC) state through mature neurons under both physiological and pathological conditions, they have been found to modulate neural cell survival, stress responses, lineage commitment, and neuronal signaling. Lineage-specific FOXO knockout mice have provided an invaluable tool for the dissection of FOXO biology in the nervous system. Within the NSC compartments of the brain, FOXOs are required for the maintenance of NSC quiescence and for the clearance of reactive oxygen species...
2018: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/29423932/protein-translation-proteolysis-and-autophagy-in-human-skeletal-muscle-atrophy-after-spinal-cord-injury
#9
L S Lundell, M Savikj, E Kostovski, P O Iversen, J R Zierath, A Krook, A V Chibalin, U Widegren
AIM: Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. METHODS: Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury...
February 8, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29415201/genetic-variation-in-foxo3-is-associated-with-self-rated-health-in-a-population-based-sample-of-older-individuals
#10
Anna Zettergren, Silke Kern, Lina Rydén, Svante Östling, Kaj Blennow, Henrik Zetterberg, Hanna Falk, Ingmar Skoog
Self-rated health (SRH) strongly predicts mortality. Twin studies estimate that genetic factors account for a substantial part of the variability in SRH. Variations in the gene FOXO3 (forkhead box O3), and in genes located at the APOE (apoplipoprotein E) locus, are associated with longevity. This study explores the relationship between SRH and genetic variation related to longevity, in a population-based cohort of older individuals. SRH was assessed among 1520 individuals aged 75 to 87, and five single nucleotide polymorphisms (SNPs), in APOE, TOMM40 (translocase of outer mitochondrial membrane 40 homolog), and FOXO3 were genotyped...
February 5, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29411515/sirt1-foxo3-axis-alteration-leads-to-aberrant-immune-responses-in-bronchial-epithelial-cells
#11
Serena Di Vincenzo, Irene H Heijink, Jacobien A Noordhoek, Chiara Cipollina, Liboria Siena, Andreina Bruno, Maria Ferraro, Dirkje S Postma, Mark Gjomarkaj, Elisabetta Pace
Inflammation and ageing are intertwined in chronic obstructive pulmonary disease (COPD). The histone deacetylase SIRT1 and the related activation of FoxO3 protect from ageing and regulate inflammation. The role of SIRT1/FoxO3 in COPD is largely unknown. This study evaluated whether cigarette smoke, by modulating the SIRT1/FoxO3 axis, affects airway epithelial pro-inflammatory responses. Human bronchial epithelial cells (16HBE) and primary bronchial epithelial cells (PBECs) from COPD patients and controls were treated with/without cigarette smoke extract (CSE), Sirtinol or FoxO3 siRNA...
April 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29344415/rhizoma-coptidis-and-berberine-as-a-natural-drug-to-combat-aging-and-aging-related-diseases-via-anti-oxidation-and-ampk-activation
#12
REVIEW
Zhifang Xu, Wei Feng, Qian Shen, Nannan Yu, Kun Yu, Shenjun Wang, Zhigang Chen, Seiji Shioda, Yi Guo
Aging is the greatest risk factor for human diseases, as it results in cellular growth arrest, impaired tissue function and metabolism, ultimately impacting life span. Two different mechanisms are thought to be primary causes of aging. One is cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK) and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive component of natural Chinese medicine rhizoma coptidis ( RC ), berberine has recently been reported to expand life span in Drosophila melanogaster, and attenuate premature cellular senescence...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29080996/impact-of-local-heating-and-cooling-on-skeletal-muscle-transcriptional-response-related-to-myogenesis-and-proteolysis
#13
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...
January 2018: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28977569/effects-of-foxo3-polymorphisms-on-survival-to-extreme-longevity-in-four-centenarian-studies
#14
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
#15
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
#16
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
#17
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 (PI3 K)/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
#18
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
#19
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
#20
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
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