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FoxO3 AND Aging

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https://www.readbyqxmd.com/read/28206976/lipid-and-alzheimer-s-disease-genes-associated-with-healthy-aging-and-longevity-in-healthy-oldest-old
#1
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...
February 11, 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
#2
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...
February 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28170423/nur77-deletion-impairs-muscle-growth-during-developmental-myogenesis-and-muscle-regeneration-in-mice
#3
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
#4
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-is-essential-for-protecting-hematopoietic-stem-and-progenitor-cells-from-oxidative-dna-damage
#5
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 importance, 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...
December 19, 2016: 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
#6
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
#7
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
#8
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...
November 29, 2016: 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
#9
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...
September 30, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27687729/forkhead-box-o3a-foxo3-and-the-mitochondrial-disulfide-relay-carrier-chchd4-regulate-p53-protein-nuclear-activity-in-response-to-exercise
#10
Jie Zhuang, William M Kamp, Jie Li, Chengyu Liu, Ju-Gyeong Kang, Ping-Yuan Wang, Paul M Hwang
Although exercise is linked with improved health, the specific molecular mechanisms underlying its various benefits require further clarification. Here we report that exercise increases the nuclear localization and activity of p53 by acutely down-regulating coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4), a carrier protein that mediates p53 import into the mitochondria. This response to exercise is lost in transgenic mice with constitutive expression of CHCHD4. Mechanistically, exercise-induced nuclear transcription factor FOXO3 binds to the CHCHD4 promoter and represses its expression, preventing the translocation of p53 to the mitochondria and thereby increasing p53 nuclear localization...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27500836/control-of-oocyte-reawakening-by-kit
#11
Hatice Duygu Saatcioglu, Ileana Cuevas, Diego H Castrillon
In mammals, females are born with finite numbers of oocytes stockpiled as primordial follicles. Oocytes are "reawakened" via an ovarian-intrinsic process that initiates their growth. The forkhead transcription factor Foxo3 controls reawakening downstream of PI3K-AKT signaling. However, the identity of the presumptive upstream cell surface receptor controlling the PI3K-AKT-Foxo3 axis has been questioned. Here we show that the receptor tyrosine kinase Kit controls reawakening. Oocyte-specific expression of a novel constitutively-active KitD818V allele resulted in female sterility and ovarian failure due to global oocyte reawakening...
August 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27402759/foxo3-regulates-neuronal-reprogramming-of-cells-from-postnatal-and-aging-mice
#12
Henrik Ahlenius, Soham Chanda, Ashley E Webb, Issa Yousif, Jesse Karmazin, Stanley B Prusiner, Anne Brunet, Thomas C Südhof, Marius Wernig
We and others have shown that embryonic and neonatal fibroblasts can be directly converted into induced neuronal (iN) cells with mature functional properties. Reprogramming of fibroblasts from adult and aged mice, however, has not yet been explored in detail. The ability to generate fully functional iN cells from aged organisms will be particularly important for in vitro modeling of diseases of old age. Here, we demonstrate production of functional iN cells from fibroblasts that were derived from mice close to the end of their lifespan...
July 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27349869/adiponectin-corrects-premature-cellular-senescence-and-normalizes-antimicrobial-peptide-levels-in-senescent-keratinocytes
#13
Taewon Jin, Min Jeong Kim, Won Il Heo, Kui Young Park, Sun Young Choi, Mi-Kyung Lee, Seung-Phil Hong, Seong-Jin Kim, Myung Im, Nam Ju Moon, Seong Jun Seo
Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3',5'-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human β-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity...
September 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27329260/genomewide-meta-analysis-identifies-loci-associated-with-igf-i-and-igfbp-3-levels-with-impact-on-age-related-traits
#14
Alexander Teumer, Qibin Qi, Maria Nethander, Hugues Aschard, Stefania Bandinelli, Marian Beekman, Sonja I Berndt, Martin Bidlingmaier, Linda Broer, Anne Cappola, Gian Paolo Ceda, Stephen Chanock, Ming-Huei Chen, Tai C Chen, Yii-Der Ida Chen, Jonathan Chung, Fabiola Del Greco Miglianico, Joel Eriksson, Luigi Ferrucci, Nele Friedrich, Carsten Gnewuch, Mark O Goodarzi, Niels Grarup, Tingwei Guo, Elke Hammer, Richard B Hayes, Andrew A Hicks, Albert Hofman, Jeanine J Houwing-Duistermaat, Frank Hu, David J Hunter, Lise L Husemoen, Aaron Isaacs, Kevin B Jacobs, Joop A M J L Janssen, John-Olov Jansson, Nico Jehmlich, Simon Johnson, Anders Juul, Magnus Karlsson, Tuomas O Kilpelainen, Peter Kovacs, Peter Kraft, Chao Li, Allan Linneberg, Yongmei Liu, Ruth J F Loos, Mattias Lorentzon, Yingchang Lu, Marcello Maggio, Reedik Magi, James Meigs, Dan Mellström, Matthias Nauck, Anne B Newman, Michael N Pollak, Peter P Pramstaller, Inga Prokopenko, Bruce M Psaty, Martin Reincke, Eric B Rimm, Jerome I Rotter, Aude Saint Pierre, Claudia Schurmann, Sudha Seshadri, Klara Sjögren, P Eline Slagboom, Howard D Strickler, Michael Stumvoll, Yousin Suh, Qi Sun, Cuilin Zhang, Johan Svensson, Toshiko Tanaka, Archana Tare, Anke Tönjes, Hae-Won Uh, Cornelia M van Duijn, Diana van Heemst, Liesbeth Vandenput, Ramachandran S Vasan, Uwe Völker, Sara M Willems, Claes Ohlsson, Henri Wallaschofski, Robert C Kaplan
The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2)...
October 2016: Aging Cell
https://www.readbyqxmd.com/read/27181414/diabetic-complications-within-the-context-of-aging-nicotinamide-adenine-dinucleotide-redox-insulin-c-peptide-sirtuin-1-liver-kinase-b1-adenosine-monophosphate-activated-protein-kinase-positive-feedback-and-forkhead-box-o3
#15
REVIEW
Yasuo Ido
Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway...
July 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27071935/the-foxo3-gene-and-cause-specific-mortality
#16
Bradley J Willcox, Gregory J Tranah, Randi Chen, Brian J Morris, Kamal H Masaki, Qimei He, D Craig Willcox, Richard C Allsopp, Stefan Moisyadi, Leonard W Poon, Beatriz Rodriguez, Anne B Newman, Tamara B Harris, Steven R Cummings, Yongmei Liu, Neeta Parimi, Daniel S Evans, Phil Davy, Mariana Gerschenson, Timothy A Donlon
The G allele of the FOXO3 single nucleotide polymorphism (SNP) rs2802292 exhibits a consistently replicated genetic association with longevity in multiple populations worldwide. The aims of this study were to quantify the mortality risk for the longevity-associated genotype and to discover the particular cause(s) of death associated with this allele in older Americans of diverse ancestry. It involved a 17-year prospective cohort study of 3584 older American men of Japanese ancestry from the Honolulu Heart Program cohort, followed by a 17-year prospective replication study of 1595 white and 1056 black elderly individuals from the Health Aging and Body Composition cohort...
August 2016: Aging Cell
https://www.readbyqxmd.com/read/26921438/tumor-necrosis-factor-%C3%AE-impairs-adiponectin-signalling-mitochondrial-biogenesis-and-myogenesis-in-primary-human-myotubes-cultures
#17
Tahnee Sente, An M Van Berendoncks, Erik Fransen, Christiaan J Vrints, Vicky Y Hoymans
Skeletal muscle metabolic changes are common in patients with chronic heart failure (HF). Previously, we demonstrated a functional skeletal muscle adiponectin resistance in HF patients with reduced left ventricular ejection fraction (HFrEF). We aimed to examine the impact of adiponectin receptor 1 (AdipoR1) deficiency and TNF-α treatment on adiponectin signaling, proliferative capacity, myogenic differentiation, and mitochondrial biogenesis in primary human skeletal muscle cells. Primary cultures of myoblasts and myotubes were initiated from the musculus vastus lateralis of 10 HFrEF patients (left ventricular ejection fraction; 31...
May 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/26873092/foxo3-circular-rna-promotes-cardiac-senescence-by-modulating-multiple-factors-associated-with-stress-and-senescence-responses
#18
William W Du, Weining Yang, Yu Chen, Zhong-Kai Wu, Francis Stuart Foster, Zhenguo Yang, Xiangmin Li, Burton B Yang
AIMS: Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches. METHODS AND RESULTS: Using the approaches of molecular and cellular biology, we show that a circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence...
February 11, 2016: European Heart Journal
https://www.readbyqxmd.com/read/26761622/effects-of-exercise-and-dietary-epigallocatechin-gallate-and-%C3%AE-alanine-on-skeletal-muscle-in-aged-mice
#19
Brandt D Pence, Trisha E Gibbons, Tushar K Bhattacharya, Houston Mach, Jessica M Ossyra, Geraldine Petr, Stephen A Martin, Lin Wang, Stanislav S Rubakhin, Jonathan V Sweedler, Robert H McCusker, Keith W Kelley, Justin S Rhodes, Rodney W Johnson, Jeffrey A Woods
Aging leads to sarcopenia and loss of physical function. We examined whether voluntary wheel running, when combined with dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) and β-alanine (β-ALA), could improve muscle function and alter gene expression in the gastrocnemius of aged mice. Seventeen-month-old BALB/cByJ mice were given access to a running wheel or remained sedentary for 41 days while receiving either AIN-93M (standard feed) or AIN-93M containing 1.5 mg·kg(-1) EGCG and 3.43 mg·kg(-1) β-ALA...
February 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/26643314/long-live-foxo-unraveling-the-role-of-foxo-proteins-in-aging-and-longevity
#20
REVIEW
Rute Martins, Gordon J Lithgow, Wolfgang Link
Aging constitutes the key risk factor for age-related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which "protective genes" are carried by long-lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity...
April 2016: Aging Cell
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