Abstract:
:The vicious cycle theory postulates that typical mitochondrial DNA (mtDNA) mutations cause their host mitochondria to generate more superoxide and other reactive oxygen species (ROS) than do normal mitochondria, thereby promoting the occurrence of additional mtDNA mutations at an ever-accelerating rate. However, nearly all the loss-of-function mtDNA mutations seen in vivo are large deletions, which (as the original statement of the theory indeed noted, though this has been widely overlooked) should not trigger a vicious cycle because they will prevent the assembly of the potentially superoxide-generating enzyme complexes. Consistent with this is the observation that each cell exhibiting loss of mtDNA-encoded function in vivo contains copies of a single, evidently clonally expanded, mutant mtDNA species, whereas the vicious cycle theory predicts a spectrum of mutant forms in each cell. Two recent papers, however, unveil a way in which mtDNA mutations could indeed promote ROS production of their host mitochondria. MtDNA mutations probably shift the intramitochondrial NAD(+)/NADH redox couple towards NADH, and this is now shown in vitro to cause ROS production by alpha-ketoglutarate dehydrogenase, an essential enzyme of the TCA cycle. This does not revive the vicious cycle theory, but it has complex implications for the two most plausible more recent theories, known as "survival of the slowest" and "crippled mitochondria." It may also prove to explain other recent observations in mitochondrially mutant cells in vivo.
journal_name
Rejuvenation Resjournal_title
Rejuvenation researchauthors
de Grey ADdoi
10.1089/rej.2005.8.13keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
13-7issue
1eissn
1549-1684issn
1557-8577journal_volume
8pub_type
杂志文章,评审abstract::To investigate whether Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula, could affect survival of aging animals, male and female C57BL/6J mice were given a VI-28-supplemented diet (0.05 and 0.5%, wt/wt) starting at 36 weeks of age, until death. VI-28 dietary supplementation at 0.05% significantly increa...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2009.0893
更新日期:2010-04-01 00:00:00
abstract::Macular degeneration is hallmarked by retinal accumulation of toxic retinoid species (e.g., A2E) for which there is no endogenous mechanism to eliminate it. This ultimately results in progressive dysfunction and loss of vision either in advanced age for genetically normal patients (age-related macular degeneration) or...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2018.2146
更新日期:2018-12-01 00:00:00
abstract::Maillard reactions are an unavoidable feature of life that appear to be damaging to cell and organisms. Consequently, all living systems must have ways to protect themselves against this process. As of 2012, several such defense mechanisms have been identified. They are all enzymatic and were found in mesophilic organ...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2012.1401
更新日期:2013-08-01 00:00:00
abstract::It is known that weakness in the lower limbs is associated with recurrent falls in old people. Among the tests routinely used to assess lower extremity strength, the Short Physical Performance Battery (SPPB) is one of those used most often, but its relationship with recurrent falls is poorly investigated. We aimed to ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2013.1491
更新日期:2014-06-01 00:00:00
abstract::Mitochondria play a central role in cellular physiology. Besides their classic function of energy metabolism, mitochondria are involved in multiple cell functions, including energy distribution through the cell, energy/heat modulation, regulation of reactive oxygen species (ROS), calcium homeostasis, and control of ap...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2015.1704
更新日期:2016-02-01 00:00:00
abstract::Advanced glycation end products are the results of a series of chemical reactions collectively known as the Maillard reaction, or nonenzymatic glycation, and sometimes cross-link proteins, thereby impairing their normal function. Glucosepane is the most abundant protein cross-link found in vivo so far and mainly has b...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2009.0846
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:This study examined the impact of estrogen replacement therapy with spirometry on pulmonary function in surgically castrated (salpingo-oophorectomy) postmenopausal women with genital prolapse. METHODS:The study included 60 postmenopausal women with pelvic organ prolapse. The study received institutional Ethi...
journal_title:Rejuvenation research
pub_type: 杂志文章,随机对照试验
doi:10.1089/rej.2012.1337
更新日期:2012-12-01 00:00:00
abstract::Theses reviewed in this issue include "Engineering Cellular Input-Output for the Robust Control of Mammalian Cell-Based Therapies"; "Enzyme-Instructed Self-Assembly (EISA) Selectively Targets Cancer Cells"; "Exploration of helminth-derived immunoregulatory molecules as options for therapeutic intervention in allograft...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2017.2001
更新日期:2017-08-01 00:00:00
abstract::Previously, other groups and our team consistently have demonstrated that the possible origination of liver cancer stem cells (LCSCs) is the malignant transformation from liver normal stem cells (LNSCs). However, this complex and multi-step process is far from clear due to the accumulation of various gene dysregulatio...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2014.1642
更新日期:2015-08-01 00:00:00
abstract::Twenty years have passed since Kadenbach and Müller-Höcker first proposed that the age-related accumulation of mutant mitochondrial DNA is caused by its clonal expansion, rather than by a "vicious cycle" of de novo mutational events caused by the disruptive metabolic impact of prior ones. Proof that they were correct ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2009.0879
更新日期:2009-06-01 00:00:00
abstract::We developed a new model for initiating, coordinating, funding, and managing biomedical research projects. The concept involves engaging the patients with chronic conditions with no known cures into goal-oriented research activities. In this model, the patient seeks the help of a research organization to bring togethe...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2013.1471
更新日期:2013-10-01 00:00:00
abstract::With advancing age, the mammalian thymus undergoes involution, a progressive loss of architectural integrity and lymphoid cellularity that results in reduced T lymphopoiesis. Thymic involution also is associated with extreme malnutrition and states of immune deficiency, such as active HIV infection, after chemotherapy...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.134
更新日期:2006-04-01 00:00:00
abstract::A hypothetical mechanism of 14C-generated influence on a person's rate of aging is offered. The mathematical description and the following approbation of the radiocarbon mechanism of aging made it possible to coordinate the Gompertz and Strehler-Mildvan laws and predict the existence of one more, till-now unknown, int...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.309
更新日期:2006-07-01 00:00:00
abstract::We investigated the prognostic role of the Short Physical Performance Battery (SPPB) in elderly patients discharged from the acute care hospital. Our series consisted of 506 patients aged 70 years or more enrolled in a multicenter collaborative observational study. We considered three main outcomes: 1-year survival af...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2011.1215
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Curcumin, an extract from the rhizome of the plant Curcuma longa (turmeric), has been widely used as a spice and herbal medicine in Asia. It has been suggested to have many biological activities, such as antioxidative, antiinflammatory, anticancer, chemopreventive, and antineurodegenerative properties. We ev...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2010.1031
更新日期:2010-10-01 00:00:00
abstract::Older patients often suffer from multiple co-morbid conditions. Few co-morbidity indices are valid and reliable in elderly patients and comparison between them is rare. Our objective was to compare the performance, relevance, and abilities of six widely used and validated co-morbidity indices--the Charlson Cumulative ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2010.1037
更新日期:2010-12-01 00:00:00
abstract::This review discusses the role of estrogens as pro- or antiinflammatory players in immune-inflammatory responses. In particular, their role in Alzheimer's disease (AD), an example of immune-inflammatory disease, is discussed briefly. AD is a progressive neurodegenerative disease, which in Western societies accounts fo...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2009.0942
更新日期:2010-04-01 00:00:00
abstract::The full power of gene modification in higher eukaryotes, including its potential to correct disease-causing mutations, has so far been limited by its low efficiency. Now that power looks set to be released through the use of customized endonuclease "hands," DNA-binding zinc fingers linked to nuclease "thumbs," capabl...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2005.8.211
更新日期:2005-01-01 00:00:00
abstract::We tried to establish an age-predictive equation from kinematic and kinetic parameters during walking using the 2007 Okada database of Japanese elderly. Some predictive equations were established for each gender (109 males and 139 females)--once for all variables, second for the stepwise variable selection method. The...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2009.0921
更新日期:2010-04-01 00:00:00
abstract::Pulses up to 11 Tesla magnetic fields may generate pockets of currents along the walls of cellular material and may interfere with the overall ability of cell division. We used prokaryotic cells (Escherichia coli) and eukaryotic cells (murine fibroblasts) and exposed them to magnetic pulses of intensities ranging from...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2013.1487
更新日期:2014-04-01 00:00:00
abstract::Alzheimer's Disease (AD) is the most common age-related dementia, with a current prevalence in excess of five million individuals in the United States. The aggregation of amyloid-beta (A beta) into fibrillar amyloid plaques is a key pathological event in the development of the disease. Microglial proinflammatory activ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2008.0757
更新日期:2008-10-01 00:00:00
abstract::Evidence suggests association of red blood cell distribution width (RDW) with cardiovascular diseases (CVDs). On the contrary, we underline that the sole RDW values cannot represent a valid CVD biomarker. High RDW values are expression of biological effects of a lot of both endogenous and exogenous factors (i.e., age,...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2018.2094
更新日期:2019-04-01 00:00:00
abstract::Aristotle described the study of politics as an "architectonic" science that aspires to bring together insights from different fields of scientific inquiry to ensure that citizens have the opportunities to flourish. To meet the health and economic challenges of aging populations, we must revive this Aristotelian visio...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2010.1023
更新日期:2010-10-01 00:00:00
abstract::The progeroid Werner's syndrome (WS) represents the best current model of human aging. It is caused by loss of the WRN helicase/exonuclease, resulting in high levels of replication fork stalling and genomic instability. Current models suggest that characteristic WS phenotypes of poor S phase progression, low prolifera...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.0503
更新日期:2007-03-01 00:00:00
abstract::It is known that dietary restriction (DR) increases maximum longevity in rodents, but the mechanisms involved remain unknown. Among the possible mechanisms, several lines of evidence support the idea that decreases in mitochondrial oxidative stress and in insulin signaling are involved but it is not known if they are ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2008.0704
更新日期:2008-06-01 00:00:00
abstract::The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing soma...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2016.1809
更新日期:2017-02-01 00:00:00
abstract::The mouse Mus musculus chromosomes are all acrocentric; each centromere (CEN) is adjacent to a telomere. The aim of the current work is to find out if at least half of the mouse telomeres (Tel) always follow satellite DNA sequences and if membrane telomere binding protein TRF2/MTBP is always in association with the Te...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.391
更新日期:2006-10-01 00:00:00
abstract::Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis Georgi. This study aimed to ascertain the effects and potential underlying mechanisms of baicalein in d-galactose (d-gal)-induced aging rat model by integration of behavior examination, biochemical detection, and 1H nuclear magnetic resonance ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2017.1919
更新日期:2017-12-01 00:00:00
abstract::Reactive oxygen species (ROS) are chemically reactive molecules with impaired electrons that make them unstable and able to react easily with a great variety of molecules. The main targets of ROS are DNA, proteins, and membrane phospholipids. In the skin, ROS are able to affect the production of collagen and elastin, ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2013.1511
更新日期:2014-06-01 00:00:00
abstract::Healthspan science aims to add healthy, functional years to human life. Many different methods of improving healthspan have been investigated, chiefly focusing on just one aspect of an organism's health such as survival. Studies in Drosophila melanogaster have demonstrated that a reversal to a long-abandoned ancestral...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2020.2361
更新日期:2020-10-20 00:00:00