An inverse-Warburg effect and the origin of Alzheimer's disease.

Abstract:

:Glycolysis and oxidative phosphorylation (OxPhos) are the two major mechanisms involved in brain energetics. In this article we propose that the sporadic forms of Alzheimer's disease (AD) are driven by age-related damage to macromolecules and organelles which results in the following series of dynamic processes. (1) Metabolic alteration: Upregulation of OxPhos activity by dysfunctional neurons. (2) Natural selection: Competition for the limited energy substrates between neurons with normal OxPhos activity [Type (1)] and dysfunctional neurons with increased OxPhos [Type (2)]. (3) Propagation, due to the fact that Type (1) neurons are outcompeted for limited substrate by Type (2) neurons which, because of increased ROS production, eventually become dysfunctional and die. Otto Warburg, in his studies of the origin of cancer, discovered that most cancer cells are characterized by an increase in glycolytic activity-a property which confers a selective advantage in oncologic environments. Accordingly, we propose the term "inverse-Warburg effect" to describe increased OxPhos activity--a property which we propose confers a selective advantage in neuronal environments, and which we hypothesize to underlie the shift from normal to pathological aging and subsequent AD.

journal_name

Biogerontology

journal_title

Biogerontology

authors

Demetrius LA,Simon DK

doi

10.1007/s10522-012-9403-6

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

583-94

issue

6

eissn

1389-5729

issn

1573-6768

journal_volume

13

pub_type

杂志文章
  • Pathways defective in the human premature aging disease Werner syndrome.

    abstract::Werner syndrome is the hallmark premature aging disease, where the patients appear much older than their chronological age. The Werner protein, defective in this disorder, is a DNA helicase and an exonuclease, and it participates in pathways of DNA repair, recombination, transcription and replication. The function and...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1023/a:1015223917491

    authors: Bohr VA,Brosh RM Jr,von Kobbe C,Opresko P,Karmakar P

    更新日期:2002-01-01 00:00:00

  • Effects of lifelong exercise and aging on the blood metabolic fingerprint of rats.

    abstract::Regular exercise is an important part of a healthy lifestyle, as it helps maintain a healthy weight and reduces the risk of chronic diseases. We explored the effects of lifelong exercise and aging on rat metabolism through a metabolomics approach. Thirty-six rats were divided into four equal groups: exercise during th...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-020-09871-1

    authors: Tzimou A,Benaki D,Nikolaidis S,Mikros E,Taitzoglou I,Mougios V

    更新日期:2020-10-01 00:00:00

  • Methionine-enkephalin modulated regulation of oxidant/antioxidant status in liver of CBA mice.

    abstract::Reactive oxygen species (ROS) are formed by all aerobic organisms, and are involved in the numerous physiological and pathophysiological processes. Opioid peptides belong to a class of bioactive compounds of great interest because of their opiate-like activity. We determined the influence of methionine-enkephalin (MEN...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-005-6040-3

    authors: Sobocanec S,Kusić B,Sverko V,Balog T,Marotti T

    更新日期:2006-02-01 00:00:00

  • Oxidative stress and intracellular pH in the young and old erythrocytes of rat.

    abstract::The effects of oxidative stress (OS) on the rat erythrocytes (RBCs) that were fractionated on the percoll/BSA gradient into young and old cells were studied to find out if the altered Na+/H+ and Cl⁻/ HCO3⁻ antiporters and in turn the intracellular pH (pHi) could act as one of the promoters of cell death. Old cells wer...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-009-9212-8

    authors: Asha Devi S,Shiva Shankar Reddy CS,Subramanyam MV

    更新日期:2009-12-01 00:00:00

  • Different adaptive traits to cold exposure in young senescence-accelerated mice.

    abstract::A reduced adaptation to cold is a prominent feature in aged mammals, including humans. The accelerated senescence-prone strain of mice (SAMP) has been studied as an animal model for several age-associated disorders and in the acceleration of senescence. Recent studies revealed that SAMP strains have dysfunctional hype...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-005-3499-x

    authors: Yamashita Y,Chiba Y,Xia C,Hirayoshi K,Satoh M,Saitoh Y,Shimada A,Nakamura E,Hosokawa M

    更新日期:2005-01-01 00:00:00

  • Altered expression pattern of Nrf2/HO-1 axis during accelerated-senescence in HIV-1 transgenic rat.

    abstract::Chronic oxidative stress plays a central role in the pathogenesis of many diseases, including HIV-1 associated disorders. Concomitantly with the decline of endogenous antioxidant systems, it was reported that HIV-1-related proteins increase the production of radical species in cells and tissues that are not directly i...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-014-9511-6

    authors: Davinelli S,Scapagnini G,Denaro F,Calabrese V,Benedetti F,Krishnan S,Curreli S,Bryant J,Zella D

    更新日期:2014-01-01 00:00:00

  • Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin.

    abstract::In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for d...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-016-9656-6

    authors: Vinod C,Jagota A

    更新日期:2016-11-01 00:00:00

  • D-galactose: a model of accelerated ageing sufficiently sensitive to reflect preventative efficacy of an antioxidant treatment.

    abstract::Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox a...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-020-09891-x

    authors: Ross KS,Smith C

    更新日期:2020-12-01 00:00:00

  • Applying parametric models to survival data: tradeoffs between statistical significance, biological plausibility, and common sense.

    abstract::Parametric models for survival data help to differentiate aging from other lifespan determinants. However, such inferences suffer from small sizes of experimental animal samples and variable animals handling by different labs. We analyzed control data from a single laboratory where interventions in murine lifespan wer...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-018-9759-3

    authors: Golubev A,Panchenko A,Anisimov V

    更新日期:2018-10-01 00:00:00

  • Gene expression in aging kidney and pituitary.

    abstract::Gene expression in aging kidney and pituitary was determined by subtractive hybridization, DNA microarrays and RT-PCR. Kidneys and pituitary were removed from 10- and 30-month-old female WAG/Rij rats, which were free from chronic progressive nephrosis and had a low incidence of pituitary tumors with age. From 350 cDNA...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1023/b:bgen.0000017685.91381.40

    authors: Preisser L,Houot L,Teillet L,Kortulewski T,Morel A,Tronik-Le Roux D,Corman B

    更新日期:2004-01-01 00:00:00

  • Ageing and the nervous system: insights from studies on invertebrates.

    abstract::Ageing can have profound effects on the post-mitotic organ of behaviour, the brain. As yet the precise causes of these deleterious effects are unknown. However, clear insights into the putative mechanisms and consequences of ageing in the CNS have been achieved through the use of invertebrate models. It is now clear t...

    journal_title:Biogerontology

    pub_type: 杂志文章,评审

    doi:10.1023/a:1011597420036

    authors: Yeoman MS,Faragher RG

    更新日期:2001-01-01 00:00:00

  • Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population.

    abstract::Associations have been reported between plasma Cu and Zn levels and the incidence of the most important age-related diseases. Previously proposed methods of using plasma Cu/Zn as a predictor of all-cause mortality have been derived from populations in which old and very old subjects were underrepresented. The purpose ...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-009-9251-1

    authors: Malavolta M,Giacconi R,Piacenza F,Santarelli L,Cipriano C,Costarelli L,Tesei S,Pierpaoli S,Basso A,Galeazzi R,Lattanzio F,Mocchegiani E

    更新日期:2010-06-01 00:00:00

  • An evolutionary heterogeneity model of late-life fecundity in Drosophila.

    abstract::There is now a significant body of research that establishes the deceleration of mortality rates in late life and their ultimate leveling off on a late-life plateau. Natural selection has been offered as one mechanism responsible for these plateaus. The force of natural selection should also exert such effects on fema...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-006-9042-x

    authors: Mueller LD,Rauser CL,Rose MR

    更新日期:2007-04-01 00:00:00

  • Age-related alterations of Apolipoprotein E and interleukin-1beta in the aging brain.

    abstract::With normal aging, the brain undergoes several alterations including reduced neuronal functioning and alterations in glia homeostasis. An increase in inflammatory signaling has also been reported in some studies of the aging brain, with inflammation potentially mediating age-related changes in the brain. Apolipoprotei...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-005-6039-9

    authors: Gee JR,Ding Q,Keller JN

    更新日期:2006-04-01 00:00:00

  • Diet (zinc)-gene interaction related to inflammatory/immune response in ageing: possible link with frailty syndrome?

    abstract::The pivotal role played by zinc-gene interaction in affecting the inflammatory response mediated by IL-6 in ageing, successful ageing (nonagenarians) and the most common age-related diseases is now recognized. Contradictory data emerging from association studies of IL-6 polymorphisms with longevity and chronic age-rel...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-010-9276-5

    authors: Mocchegiani E,Basso A,Giacconi R,Piacenza F,Costarelli L,Pierpaoli S,Malavolta M

    更新日期:2010-10-01 00:00:00

  • A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults.

    abstract::The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS a...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-015-9570-3

    authors: Oka S,Hirai J,Yasukawa T,Nakahara Y,Inoue YH

    更新日期:2015-08-01 00:00:00

  • From bench to bedside and back: the SENIEUR Protocol and the efficacy of influenza vaccination in the elderly.

    abstract::Prophylaxis with vaccines is important in geriatrics as, apart from specific protection, it reduces incidence of potentially fatal infectious complications and exacerbations of existing medical conditions. Post-vaccination protection depends on immunity and therefore markers of immune status could be used to predict e...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-008-9155-5

    authors: Trzonkowski P,Myśliwska J,Pawelec G,Myśliwski A

    更新日期:2009-02-01 00:00:00

  • Impairment of regeneration in aging: appropriateness or stochastics?

    abstract::There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. We believe that the restri...

    journal_title:Biogerontology

    pub_type: 杂志文章,评审

    doi:10.1007/s10522-013-9468-x

    authors: Khokhlov AN

    更新日期:2013-12-01 00:00:00

  • Convergence of longevity and immunity: lessons from animal models.

    abstract::An increasing amount of data implicate immunity-mostly innate immunity-in the ageing process; both during healthy ageing as well as in neurodegenerative diseases. Despite the aetiology however, the underlying mechanisms are poorly understood. Here we review what we know from model organisms (worms, flies and mice) on ...

    journal_title:Biogerontology

    pub_type: 杂志文章,评审

    doi:10.1007/s10522-019-09801-w

    authors: Xia J,Gravato-Nobre M,Ligoxygakis P

    更新日期:2019-06-01 00:00:00

  • The impact of obesity on skeletal muscle strength and structure through adolescence to old age.

    abstract::Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance limitations. The consensus is that obese individuals, regardless of age, have a greater absolute maximum muscle strength compar...

    journal_title:Biogerontology

    pub_type: 杂志文章,评审

    doi:10.1007/s10522-015-9626-4

    authors: Tomlinson DJ,Erskine RM,Morse CI,Winwood K,Onambélé-Pearson G

    更新日期:2016-06-01 00:00:00

  • Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans.

    abstract::Accumulating studies have argued that the mitochondrial unfolded protein response (UPRmt) is a mitochondrial stress response that promotes longevity in model organisms. In the present study, we screened an off-patent drug library to identify compounds that activate UPRmt using a mitochondrial chaperone hsp-6::GFP repo...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-020-09907-6

    authors: Ito A,Zhao Q,Tanaka Y,Yasui M,Katayama R,Sun S,Tanimoto Y,Nishikawa Y,Kage-Nakadai E

    更新日期:2021-02-01 00:00:00

  • A mild stress due to hypergravity exposure at young age increases longevity in Drosophila melanogaster males.

    abstract::Drosophila melanogaster flies were exposed to hypergravity starting at two days of age, the range of gravity levels used being 2.58-7.38 g. No longevity change was observed for exposures of less than 14 days. The longevity of males increased if they were submitted to hypergravity for durations ranging from 14 to 24 da...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1023/a:1010043914016

    authors: Le Bourg E,Minois N,Bullens P,Baret P

    更新日期:2000-01-01 00:00:00

  • Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43.

    abstract::The nematode Caenorhabditis elegans responds to flavonoid-rich diets with improved health and longevity. The precise mechanism(s) responsible for this remains to be identified, but is believed to be linked to the highly antioxidative properties of flavonoids. This study provides a dissection of lifespan modulation by ...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-008-9199-6

    authors: Pietsch K,Saul N,Menzel R,Stürzenbaum SR,Steinberg CE

    更新日期:2009-10-01 00:00:00

  • How regularities of mortality statistics explain why we age despite having potentially ageless somatic stem cells.

    abstract::Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, r...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-017-9728-2

    authors: Khalyavkin AV,Krut'ko VN

    更新日期:2018-02-01 00:00:00

  • Life extension in Drosophila maintained under lengthened light/dark regime.

    abstract::In the present study, we investigated whether the length of light/dark cycle could influence the pre-adult developmental time and adult life span in Drosophila melanogaster. Flies were reared to adulthood and maintained as adults under both 24-h (light/dark 12:12 h) and 48-h (light/dark 24:24 h) cycles. The flies rear...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-008-9146-6

    authors: Vaiserman AM,Pisaruck AV,Timchenko AN,Voitenko VP,Koshel NM,Grigoriev PE

    更新日期:2008-10-01 00:00:00

  • Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms?

    abstract::The predominant molecular symptom of ageing is the accumulation of altered gene products. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin activity. P...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-007-9110-x

    authors: Hipkiss AR

    更新日期:2008-02-01 00:00:00

  • Age-specificity and the evolution of senescence: a discussion.

    abstract::Senescence evolved because selection pressure declines with age. However, to explain senescence it does not suffice to demonstrate that selection pressure declines. It is also necessary to postulate biological mechanisms that lead to a deteriorated state of the organism at high ages, but not before. This has lead to t...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-012-9410-7

    authors: Wensink M

    更新日期:2013-02-01 00:00:00

  • Reserpine can confer stress tolerance and lifespan extension in the nematode C. elegans.

    abstract::Though the lifespan extension mechanism is partly understood from C. elegans to mice, a viable pharmacological intervention is not yet feasible. Here, we report that reserpine largely known as an antipsychotic-antihypertensive drug, can extend C. elegans lifespan. Chronic reserpine treatment from embryo stage or young...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-008-9139-5

    authors: Srivastava D,Arya U,SoundaraRajan T,Dwivedi H,Kumar S,Subramaniam JR

    更新日期:2008-10-01 00:00:00

  • Protein thiol oxidation does not change in skeletal muscles of aging female mice.

    abstract::Oxidative stress caused by reactive oxygen species is proposed to cause age related muscle wasting (sarcopenia). Reversible oxidation of protein thiols by reactive oxygen species can affect protein function, so we evaluated whether muscle wasting in normal aging was associated with a pervasive increase in reversible o...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-013-9483-y

    authors: Tohma H,El-Shafey AF,Croft K,Shavlakadze T,Grounds MD,Arthur PG

    更新日期:2014-02-01 00:00:00

  • Mitochondrial biogenesis and neural differentiation of human iPSC is modulated by idebenone in a developmental stage-dependent manner.

    abstract::Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular respon...

    journal_title:Biogerontology

    pub_type: 杂志文章

    doi:10.1007/s10522-017-9718-4

    authors: Augustyniak J,Lenart J,Zychowicz M,Stepien PP,Buzanska L

    更新日期:2017-08-01 00:00:00