Rapamycin-induced metabolic defects are reversible in both lean and obese mice.

Abstract:

:The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated. Here, we confirmed that rapamycin causes glucose intolerance and insulin resistance in both inbred and genetically heterogeneous mice fed either low fat or high fat diets, suggesting that these effects of rapamycin are independent of genetic background. Importantly, we also found that these effects were almost completely lost within a few weeks of cessation of treatment, showing that chronic rapamycin treatment does not induce permanent impairment of glucose metabolism. Somewhat surprisingly, chronic rapamycin also promoted increased accumulation of adipose tissue in high fat fed mice. However, this effect too was lost when rapamycin treatment was ended suggesting that this effect of rapamycin is also not permanent. The reversible nature of rapamycin's alterations of metabolic function suggests that these potentially detrimental side-effects might be managed through alternative dosing strategies or concurrent treatment options.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Liu Y,Diaz V,Fernandez E,Strong R,Ye L,Baur JA,Lamming DW,Richardson A,Salmon AB

doi

10.18632/aging.100688

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

742-54

issue

9

issn

1945-4589

pii

100688

journal_volume

6

pub_type

杂志文章

相关文献

Aging-US文献大全
  • Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis.

    abstract::A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administr...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100207

    authors: Yoshida N,Maejima Y,Sedbazar U,Ando A,Kurita H,Damdindorj B,Takano E,Gantulga D,Iwasaki Y,Kurashina T,Onaka T,Dezaki K,Nakata M,Mori M,Yada T

    更新日期:2010-11-01 00:00:00

  • Elevated systemic inflammatory responses, factors associated with physical and mental quality of life, and prognosis of hepatocellular carcinoma.

    abstract::Impaired quality of life (QOL) is common in hepatocellular carcinoma (HCC) patients. In this study, we used a large hospital-based multiethnic HCC patient cohort to systematically identify factors associated with QOL and investigate the prognostic value of QOL.The Short Form-12 questionnaire was used to assess QOL. Th...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102889

    authors: Deng Y,Zhu J,Liu Z,Huang M,Chang DW,Gu J

    更新日期:2020-03-07 00:00:00

  • Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span.

    abstract::Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101009

    authors: Gat-Yablonski G,Finka A,Pinto G,Quadroni M,Shtaif B,Goloubinoff P

    更新日期:2016-08-01 00:00:00

  • Modelling biological age based on plasma peptides in Han Chinese adults.

    abstract::Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mas...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103286

    authors: Cao W,Zheng D,Wang G,Zhang J,Ge S,Singh M,Wang H,Song M,Li D,Wang W,Xu X,Wang Y

    更新日期:2020-06-05 00:00:00

  • High expression of the breast cancer susceptibility gene BRCA1 in long-lived termite kings.

    abstract::Aging is associated with the accumulation of DNA damage. High expression of DNA repair genes has been suggested to contribute to prolonged lifespan in several organisms. However, the crucial DNA repair genes contributing to longevity remain unknown. Termite kings have an extraordinary long lifespan compared with that ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101578

    authors: Tasaki E,Mitaka Y,Nozaki T,Kobayashi K,Matsuura K,Iuchi Y

    更新日期:2018-10-11 00:00:00

  • miR-183-5p alleviates early injury after intracerebral hemorrhage by inhibiting heme oxygenase-1 expression.

    abstract::Differences in microRNA (miRNA) expression after intracerebral hemorrhage (ICH) have been reported in human and animal models, and miRNAs are being investigated as a new treatment for inflammation and oxidative stress after ICH. In this study, we found that microRNA-183-5p expression was decreased in the mouse brain a...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103343

    authors: Wang Y,Song Y,Pang Y,Yu Z,Hua W,Gu Y,Qi J,Wu H

    更新日期:2020-06-29 00:00:00

  • Evaluation of the diagnostic ability of laminin gene family for pancreatic ductal adenocarcinoma.

    abstract::A poor outcome for pancreatic ductal adenocarcinoma (PDAC) patients is still a challenge worldwide. The aim of our study is to investigate the potential of key laminin subunits for being used both as a diagnostic and prognostic biomarker for PDAC patients. We evaluated the mRNA expression and prognostic value of lamin...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102007

    authors: Yang C,Liu Z,Zeng X,Wu Q,Liao X,Wang X,Han C,Yu T,Zhu G,Qin W,Peng T

    更新日期:2019-06-10 00:00:00

  • Methionine abrogates the renoprotective effect of a low-protein diet against diabetic kidney disease in obese rats with type 2 diabetes.

    abstract::Dietary interventions, including a low-protein diet (LPD) and methionine (Met) restriction, have shown longevity, anti-aging and metabolic health effects. We previously reported that the LPD has a renoprotective effect against diabetic kidney disease (DKD) in rats with type 2 diabetes and obesity. However, it is uncle...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102902

    authors: Kitada M,Ogura Y,Monno I,Xu J,Koya D

    更新日期:2020-03-06 00:00:00

  • SNRPB-mediated RNA splicing drives tumor cell proliferation and stemness in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the leading malignant diseases worldwide, but therapeutic targets for HCC are lacking. Here, we characterized a significant upregulation of Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) in HCC via qRT-PCR, western blotting, tissue microarray and public database ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202164

    authors: Zhan YT,Li L,Zeng TT,Zhou NN,Guan XY,Li Y

    更新日期:2020-12-03 00:00:00

  • Tree-based classification system incorporating the HVTT-PVTT score for personalized management of hepatocellular carcinoma patients with macroscopic vascular invasion.

    abstract:PURPOSE:To develop a decision tree algorithm-based classification system for personalized management of hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion. RESULTS:The HVTT-PVTT score could differentiate two groups of patients (< 3 and ≥ 3 points) with different survival outcomes (7.4 vs 4.6 mo...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102403

    authors: Cao F,Shen L,Qi H,Xie L,Song Z,Chen S,Fan W

    更新日期:2019-11-03 00:00:00

  • Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway.

    abstract::Osteosarcoma (OS) is the most common bone tumor in children and adolescents and is characterized by high metastatic and recurrence rates. In the past, it has been shown that microRNAs may play critical roles in hypoxia-related OS proliferation and invasion. However, the mechanisms by which OS cells acquire this malign...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103049

    authors: Chen G,Gu H,Fang T,Zhou K,Xu J,Yin X

    更新日期:2020-04-17 00:00:00

  • Complete cardiac regeneration in a mouse model of myocardial infarction.

    abstract::Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100526

    authors: Haubner BJ,Adamowicz-Brice M,Khadayate S,Tiefenthaler V,Metzler B,Aitman T,Penninger JM

    更新日期:2012-12-01 00:00:00

  • Skin aging: are adipocytes the next target?

    abstract::Dermal white adipose tissue (dWAT) is increasingly appreciated as a special fat depot. The adipocytes in this depot exert a variety of unique effects on their surrounding cells and can undergo massive phenotypic changes. Significant modulation of dWAT content can be observed both in intrinsically and extrinsically age...

    journal_title:Aging

    pub_type: 杂志文章,评审

    doi:10.18632/aging.100999

    authors: Kruglikov IL,Scherer PE

    更新日期:2016-07-01 00:00:00

  • TNFAIP3 ameliorates the degeneration of inflammatory human nucleus pulposus cells by inhibiting mTOR signaling and promoting autophagy.

    abstract::Autophagy is involved in degenerative diseases such as osteoarthritis and disc degeneration. Although, tumor necrosis factor α-induced protein 3 (TNFAIP3) is well-known as a key regulator of inflammation and autophagy, it is still not clear whether TNFAIP3 regulates autophagy to protect from human disc cells degenerat...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.104160

    authors: Chen J,Ma Y,Yang Z,Lan H,Liu G,Zhang Y,Xia H,Wang X,Han F,Tu X,Liu B

    更新日期:2020-11-20 00:00:00

  • Extracellular vesicles derived from microRNA-150-5p-overexpressing mesenchymal stem cells protect rat hearts against ischemia/reperfusion.

    abstract::An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-inte...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102792

    authors: Ou H,Teng H,Qin Y,Luo X,Yang P,Zhang W,Chen W,Lv D,Tang H

    更新日期:2020-07-13 00:00:00

  • Immune profile of the tumor microenvironment and the identification of a four-gene signature for lung adenocarcinoma.

    abstract::The composition and relative abundances of immune cells in the tumor microenvironment are key factors affecting the progression of lung adenocarcinomas (LUADs) and the efficacy of immunotherapy. Using the cancer gene expression dataset from The Cancer Genome Atlas (TCGA) program, we scored stromal and immune cells for...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202269

    authors: Fan T,Zhu M,Wang L,Liu Y,Tian H,Zheng Y,Tan F,Sun N,Li C,He J

    更新日期:2020-12-09 00:00:00

  • LncRNA SOCS2-AS1 inhibits progression and metastasis of colorectal cancer through stabilizing SOCS2 and sponging miR-1264.

    abstract::Abnormal expression of long noncoding RNA (lncRNA) is involved in human cancers, including colorectal cancer (CRC). However, their functional mechanism is largely unknown. In this study, we explored the roles of lncRNA SOCS2-AS1 in modulating CRC progression. We showed that SOCS2-AS1 was lowly expressed in CRC tissues...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103276

    authors: Zheng Z,Li X,You H,Zheng X,Ruan X

    更新日期:2020-05-21 00:00:00

  • Attenuation of constitutive DNA damage signaling by 1,25-dihydroxyvitamin D3.

    abstract::In addition to its traditional role in the regulation of calcium homeostasis and bone metabolism, vitamin D also exhibits immunomodulatory, anti-proliferative and cancer preventive activities. Molecular mechanisms that confer the chemo-preventive properties to vitamin D are poorly understood. We previously reported th...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100450

    authors: Halicka HD,Zhao H,Li J,Traganos F,Studzinski GP,Darzynkiewicz Z

    更新日期:2012-04-01 00:00:00

  • Loss of AKR1B10 promotes colorectal cancer cells proliferation and migration via regulating FGF1-dependent pathway.

    abstract::Colorectal cancer (CRC) is a common malignancy worldwide with poor prognosis and survival rates. The aldo-keto reductase family 1 member B10 (AKR1B10) plays an important role in metabolism, cell proliferation and mobility, and is downregulated in CRC. We hypothesized that AKR1B10 would promote CRC genesis via a noncan...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103393

    authors: Yao Y,Wang X,Zhou D,Li H,Qian H,Zhang J,Jiang L,Wang B,Lin Q,Zhu X

    更新日期:2020-07-02 00:00:00

  • MiR-191 inhibit angiogenesis after acute ischemic stroke targeting VEZF1.

    abstract::Acute ischemic stroke (AIS) is a major public health problem in China. Impaired angiogenesis plays crucial roles in the development of ischemic cerebral injury. Recent studies have identified that microRNAs (miRNAs) are important regulators of angiogenesis, but little is known the exact effects of angiogenesis-associa...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101948

    authors: Du K,Zhao C,Wang L,Wang Y,Zhang KZ,Shen XY,Sun HX,Gao W,Lu X

    更新日期:2019-05-07 00:00:00

  • Assessment of ERBB2 and TOP2α gene status and expression profile in feline mammary tumors: findings and guidelines.

    abstract::In humans, the ERBB2 gene amplification and overexpression are biomarkers for invasive breast cancer and a therapeutic target. Also, TOP2α gene aberrations predict the response to anthracycline-based adjuvant chemotherapy. Although feline mammary tumors (FMTs) are good models in comparative oncology, scarce data is av...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102079

    authors: Ferreira D,Soares M,Correia J,Adega F,Ferreira F,Chaves R

    更新日期:2019-07-12 00:00:00

  • TP53 and MTOR crosstalk to regulate cellular senescence.

    abstract::The full spectrum of activities of the tumor suppressor p53 (TP53) has not been completely elucidated yet. Recently, it was demonstrated that TP53 communicates with the metabolic regulator mechanistic target of rapamycin (MTOR) to determine whether stressed cells undergo cell death, reversible quiescence or irreversib...

    journal_title:Aging

    pub_type: 社论

    doi:10.18632/aging.100202

    authors: Galluzzi L,Kepp O,Kroemer G

    更新日期:2010-09-01 00:00:00

  • Age-related micro-RNA abundance in individual C. elegans.

    abstract::Non-coding small RNAs of the micro-RNA class (miRNA) are conserved regulators of gene function with a broad impact on biological processes. We screened miRNA levels for age-related changes in individual worms and investigated their influence on the lifespan of the nematode C. elegans. We measured the abundance of 69 m...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100564

    authors: Lucanic M,Graham J,Scott G,Bhaumik D,Benz CC,Hubbard A,Lithgow GJ,Melov S

    更新日期:2013-06-01 00:00:00

  • Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

    abstract::Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100882

    authors: Bartley JM,Pan SJ,Keilich SR,Hopkins JW,Al-Naggar IM,Kuchel GA,Haynes L

    更新日期:2016-04-01 00:00:00

  • Mitochondrial replacement in an iPSC model of Leber's hereditary optic neuropathy.

    abstract::Cybrid technology was used to replace Leber hereditary optic neuropathy (LHON) causing mitochondrial DNA (mtDNA) mutations from patient-specific fibroblasts with wildtype mtDNA, and mutation-free induced pluripotent stem cells (iPSCs) were generated subsequently. Retinal ganglion cell (RGC) differentiation demonstrate...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101231

    authors: Wong RCB,Lim SY,Hung SSC,Jackson S,Khan S,Van Bergen NJ,De Smit E,Liang HH,Kearns LS,Clarke L,Mackey DA,Hewitt AW,Trounce IA,Pébay A

    更新日期:2017-04-01 00:00:00

  • A single-nucleotide polymorphism (rs1805087) in the methionine synthase (METH) gene increases the risk of prostate cancer.

    abstract::Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between METH gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of METH single-nuc...

    journal_title:Aging

    pub_type: 杂志文章,meta分析,评审

    doi:10.18632/aging.101584

    authors: Zhang X,Tang J,Shen N,Ren K

    更新日期:2018-10-18 00:00:00

  • Correlates of change in accelerometer-assessed total sedentary time and prolonged sedentary bouts among older English adults: results from five-year follow-up in the EPIC-Norfolk cohort.

    abstract:BACKGROUND:Development of effective strategies to reduce sedentary time among older adults necessitates understanding of its determinants but longitudinal studies of this utilising objective measures are scarce. METHODS:Among 1536 older adults (≥60 years) in the EPIC-Norfolk study, sedentary time was assessed for seve...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202497

    authors: Yerrakalva D,Hajna S,Wijndaele K,Westgate K,Khaw KT,Wareham N,Griffin SJ,Brage S

    更新日期:2021-01-11 00:00:00

  • Caloric restriction effects on liver mTOR signaling are time-of-day dependent.

    abstract::The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101498

    authors: Tulsian R,Velingkaar N,Kondratov R

    更新日期:2018-07-16 00:00:00

  • Age-related hearing loss accelerates cerebrospinal fluid tau levels and brain atrophy: a longitudinal study.

    abstract::Age-related hearing loss (ARHL) has been considered as a promising modifiable risk factor for cognitive impairment and dementia. Nonetheless, it is still unclear whether age-related hearing loss associates with neurodegenerative biomarkers of Alzheimer's disease (AD). Participants with ARHL were selected from the esta...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101971

    authors: Xu W,Zhang C,Li JQ,Tan CC,Cao XP,Tan L,Yu JT,Alzheimer’s Disease Neuroimaging Initiative.

    更新日期:2019-05-22 00:00:00

  • Long noncoding RNA LINC00461 induced osteoarthritis progression by inhibiting miR-30a-5p.

    abstract::Mounting studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development and occurrence of several human diseases. However, the role of LINC00461 in osteoarthritis (OA) remains obscure. A CCK-8 assay was performed to detect cell viability, and qRT-PCR analysis was used to measure mRNA exp...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102839

    authors: Zhang Y,Ma L,Wang C,Wang L,Guo Y,Wang G

    更新日期:2020-03-10 00:00:00