Abstract:
:The Mitochondrial Free Radical Theory of Aging (MFRTA) is currently one of the most widely accepted theories used to explain aging. From MFRTA three basic predictions can be made: long-lived individuals or species should produce fewer mitochondrial Reactive Oxygen Species (mtROS) than short-lived individuals or species; a decrease in mtROS production will increase lifespan; and an increase in mtROS production will decrease lifespan. It is possible to add a further fourth prediction: if ROS is controlling longevity separating these parameters through selection would be impossible. These predictions have been tested in Drosophila melanogaster. Firstly, we studied levels of mtROS production and lifespan of three wild-type strains of Drosophila, Oregon R, Canton S and Dahomey. Oregon R flies live the longest and produce significantly fewer mtROS than both Canton S and Dahomey. These results are therefore in accordance with the first prediction. A new transgenic Drosophila model expressing the Ciona intestinalis Alternative Oxidase (AOX) was used to test the second prediction. In fungi and plants, AOX expression regulates both free radical production and lifespan. In Drosophila, AOX expression decreases mtROS production, but does not increase lifespan. This result contradicts the second prediction of MFRTA. The third prediction was tested in flies mutant for the gene dj-1beta. These flies are characterized by an age-associated decline in locomotor function and increased levels of mtROS production. Nevertheless, dj-1beta mutant flies do not display decreased lifespan, which again is in contradiction with MFRTA. In our final experiment we utilized flies with DAH mitochondrial DNA in an OR nuclear background, and OR mitochondrial DNA in DAH nuclear background. From this, Mitochondrial DNA does not control free radical production, but it does determine longevity of females independently of mtROS production. In summary, these results do not systematically support the predictions of the MFRTA. Accordingly, MFRTA should be revised to accommodate these findings.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Sanz A,Fernández-Ayala DJ,Stefanatos RK,Jacobs HTdoi
10.18632/aging.100137subject
Has Abstractpub_date
2010-04-01 00:00:00pages
200-23issue
4issn
1945-4589pii
v2/n4/full/100137.htmljournal_volume
2pub_type
杂志文章相关文献
Aging-US文献大全abstract::Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug administered with chemotherapy, on radiation-induced heart disease (RIHD) in a rat model. Male Sprague-Dawley rats were irradiated with a single dose of 2...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202332
更新日期:2021-01-02 00:00:00
abstract:OBJECTIVE:This study aimed to explore the effect of silencing hTERT on the CSC-like characteristics and radioresistance of CNE-2R cells. RESULTS:Silencing hTERT suppressed CNE-2R cell proliferation and increased the cell apoptosis rate and radiosensitivity in vitro. Moreover, it could also inhibit the growth of xenogr...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.104167
更新日期:2020-11-24 00:00:00
abstract::Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obvi...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103233
更新日期:2020-05-15 00:00:00
abstract::Previous studies have indicated a correlation between nut intake and cancer risk in humans. This meta-analysis aimed to determine the relationship between nut consumption and the risks of cancer incidence and mortality. The PubMed, Embase, and Web of Science databases were searched up to August 2019. Relative risks an...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103292
更新日期:2020-06-02 00:00:00
abstract::Although observational studies have reported a positive association between obstructive sleep apnea syndrome (OSAS) and breast cancer (BC) risk, causality remains inconclusive. We aim to explore whether OSAS is associated with etiology of BC by conducting a two-sample Mendelian randomization (MR) study in a Chinese po...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102725
更新日期:2020-02-29 00:00:00
abstract::Circular RNAs (circRNAs), a novel class of endogenous long non-coding RNAs, have attracted considerable attention due to their closed continuous loop structure and potential clinical value. In this study, we investigated the function of circFASTKD1 in vascular endothelial cells. CircFASTKD1 bound directly to miR-106a ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202305
更新日期:2020-12-19 00:00:00
abstract::There are various factors that alter physiological characteristics in skin. Elucidating the underlying mechanism of transcriptional alterations by intrinsic and extrinsic factors may lead us to understand the aging process of skin. To identify the transcriptomic changes of the aging skin, we analyzed publicly availabl...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101496
更新日期:2018-07-18 00:00:00
abstract:BACKGROUND:Nucleus accumbens-associated protein 1 (NAC1) has multifaceted roles in cancer pathogenesis and progression, including the development of drug resistance, promotion of cytokinesis, and maintenance of "stem cell-like" phenotypes. NAC1 is a transcriptional co-regulator belonging to the bric-a-brac tramtrack br...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103203
更新日期:2020-05-14 00:00:00
abstract:INTRODUCTION:Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited. METHODS:Based on bioinformatic analysis, in vitro and in vivo studies were perf...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202388
更新日期:2021-01-20 00:00:00
abstract::The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including can...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100523
更新日期:2012-12-01 00:00:00
abstract::Epigenetic regulation of various genomic functions, including gene expression, provide mechanisms whereby an organism can dynamically respond to changes in its environment and modify gene expression accordingly. One epigenetic mechanism implicated in human aging and age-related disorders is DNA methylation. Isolated p...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101187
更新日期:2017-02-28 00:00:00
abstract::We hypothesize that altered intensities of a few morphogenic pathways account for most/all the phenotypes of aging. Investigating this has revealed a novel approach to rejuvenate multiple mammalian tissues by defined pharmacology. Specifically, we pursued the simultaneous youthful in vivo calibration of two determinan...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102148
更新日期:2019-08-15 00:00:00
abstract::Aging is associated with reduced tissue remodeling efficiency and increased fibrosis, characterized by excess collagen accumulation and altered matrix degradation. Ovulation, the process by which an egg is released from the ovary, is one of the most dynamic cycles of tissue wounding and repair. Because the ovary is on...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103237
更新日期:2020-05-14 00:00:00
abstract::Hyperglycemia impairs insulin secretion as well as insulin action, being recognized as the glucotoxicity that accelerates diabetes. However, the mechanism underlying the glucotoxicity in pancreatic β-cells is not thoroughly understood. Hyperglycemia alters glucose metabolism within β-cells and interstitial conditions ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100647
更新日期:2014-03-01 00:00:00
abstract::Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of D...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100973
更新日期:2016-06-01 00:00:00
abstract::Advanced age and apolipoprotein E (APOE) ε4 allele are both associated with increased risk of the Alzheimer's disease (AD). However, the extent of the joint contribution of APOE ε4 allele and age on the brain white matter integrity, cognition and their relationship are unclear. We assessed the age-related variation di...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103367
更新日期:2020-06-22 00:00:00
abstract::Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression le...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103241
更新日期:2020-05-12 00:00:00
abstract::SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE(-/-) mice and human patients. However, the role of SIRT6 in regulating vascular endothelia...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100975
更新日期:2016-05-01 00:00:00
abstract::Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101908
更新日期:2019-04-14 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC), a major histologic subtype of head and neck cancer, presents great mortality and morbidity worldwide. The aim of this study is to discover new potential biomarkers closely correlated with HNSCC progression. In this study, weighted gene co-expression network analysis was a...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102000
更新日期:2019-06-06 00:00:00
abstract:BACKGROUND:Long non-coding RNAs (LncRNAs) have been associated with several types of cancer. However, little is known about their role in lung adenocarcinoma (LUAD). RESULTS:LINC00968 was significantly differentially expressed in LUAD tissues. Downregulated LINC00968 was associated with clinicopathological features of...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.104011
更新日期:2020-11-04 00:00:00
abstract::Recent experimental studies highlighted the role of hydrogen sulfide (H2S) in aging and longevity. The cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are the key enzymes responsible for H2S production. Here we investigated the geroprotective effects of CSE and CBS overexpression in Drosophila. Overexpr...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101630
更新日期:2018-11-08 00:00:00
abstract::DNA damaging agents and radiation, cytotoxins and anti-cancer drugs, telomere erosion and cytokines, culture shock and mitogenic stimuli, oncogenes and tumor suppressors can induce both cell cycle arrest and cellular senescence. Due to this semi-coincidence, senescence is confused with cell cycle arrest, or even more ...
journal_title:Aging
pub_type: 杂志文章,评审
doi:10.18632/aging.100281
更新日期:2011-02-01 00:00:00
abstract::Mounting evidence suggests that noncoding RNAs (ncRNAs) contribute to the pathogenesis of cardiovascular diseases. However, their role in essential hypertension (EH) is still unclear. We therefore identified differentially expressed long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in EH patients from a high-...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103137
更新日期:2020-05-11 00:00:00
abstract::Endometrial cancer (EC) is one of the most common gynecologic malignancies. To identify potential prognostic biomarkers for EC, we analyzed the relationship between the EC tumor microenvironment and gene expression profiles. Using the ESTIMATE R tool, we found that immune and stromal scores correlated with clinical da...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102817
更新日期:2020-02-19 00:00:00
abstract::Numerous studies have investigated the differences in the mean functional connectivity (FC) strength between amnestic mild cognitive impairment (aMCI) patients and normal subjects using resting-state functional magnetic resonance imaging. However, whether the mean FC is increased, decreased or unchanged in aMCI patien...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102986
更新日期:2020-04-01 00:00:00
abstract::In this study, we investigated the role of macrophage stimulating 1 (Mst1) and the AMPK-Sirt1 signaling pathway in the oxidative stress-induced mitochondrial dysfunction and apoptosis seen in rheumatoid arthritis-related fibroblast-like synoviocytes (RA-FLSs). Mst1 mRNA and protein expression was significantly higher ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103643
更新日期:2020-07-21 00:00:00
abstract::Wilms tumor is a type of pediatric solid tumor that arises partly due to somatic and germline mutations. Single-nucleotide polymorphisms (SNPs) in the RAS gene reportedly modify the risk for several types of human malignancies. We conducted a multicenter study to investigate whether RAS gene variants predispose indivi...
journal_title:Aging
pub_type: 杂志文章,多中心研究
doi:10.18632/aging.101855
更新日期:2019-03-12 00:00:00
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
更新日期:2018-10-18 00:00:00
abstract::Although mechanical forces are involved in pressure-overloaded cardiomyopathy, their effects on gene transcription profiles are not fully understood. Here, we used next-generation sequencing (NGS) to investigate changes in genomic profiles after cyclic mechanical stretching of human cardiomyocytes. We found that 85, 8...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103465
更新日期:2020-08-05 00:00:00