Cited by 430Mitochondrial Function and PathologyCoenzyme Q10 studies and effectsBioactive Compounds and Antitumor Agents

An Attempt to Prevent Senescence: A Mitochondrial Approach

Open access
Skulachev, Vladimir P., Anisimov, Vladimir N., Antonenko, Yuri N., Bakeeva, Lora E., Chernyak, Boris V., Erichev, Valery P., Filenko, Oleg F., Kalinina, Natalya I. +19 more·2009·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Abstract

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM, isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic quinone derivatives were found to be prooxidants, but at lower (sub-micromolar) concentrations they displayed antioxidant activity that decreases in the series SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ derivative, stained only one type of organelles, namely mitochondria. Extremely low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia, torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of sight in rabbits with experimental uveitis and restored vision to animals that had already become blind. A favorable effect of the same drops was also achieved in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the isolated heart. SkQs strongly reduced the damaged area in myocardial infarction or stroke and prevented the death of animals from kidney ischemia. In p53(-/-) mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited appearance of lymphomas to the same degree as million-fold higher concentration of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for treatment of senescence and age-related diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bbabio.2008.12.008

Cites

146 of 146 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Benefits of SkQ1 and SkQR1 were achieved in vivo in a wide range of age-related diseases and across species, even with low doses administered later in life.

    “Moreover, these benefits were achieved also in vivo in a wide range of age-related diseases and across species, even in the case of low doses administration later in life [74,76,97].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., Kopnin, B. P., Korshunova, G. A., Lichinitser, M. R., Obukhova, L. A., Pasyukova, E. G., Pisarenko, O. I., Roginsky, V. A., Ruuge, E. K., Senin, I. I., Severina, I. I., Skulachev, M. V., Spivak, I. M., Tashlitsky, V. N., Tkachuk, V. A., Vyssokikh, M. Y., Yaguzhinsky, L. S., & Zorov, D. B.
Affiliations
  • Lomonosov Moscow State University (RU)
  • Institute of Oncology NN Petrov (RU)
  • Institute of Experimental Cardiology (RU)
  • Russian Cancer Research Center NN Blokhin (RU)
  • Novosibirsk State University (RU)
  • Russian Academy of Sciences (RU)
  • Semenov Institute of Chemical Physics (RU)
Corresponding author
Skulachev, Vladimir P.
Venue
Biochimica et Biophysica Acta (BBA) - Bioenergetics
Publisher
Elsevier BV
Published
2009-05
Volume
1787
Issue
5
Pages
437-461
ISSN
0005-2728 (ISSN-L)
OpenAlex
W2012309329
Cited by
430
References
146
Citations by year
2026: 13 · 2025: 11 · 2024: 13 · 2023: 19 · 2022: 15 · 2021: 25 · 2020: 23 · 2019: 19 · 2018: 31 · 2017: 23 · 2016: 31 · 2015: 26 · 2014: 32 · 2013: 35 · 2012: 30
FWCI
2.08
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education and Science of the Russian Federation
  • Midlands State University
  • Lomonosov Moscow State University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
mitochondrial antioxidants, plastoquinone, MitoQ, mitochondrial permeability transition, cardiolipin oxidation, reactive oxygen species, aging, lifespan extension, apoptosis, necrosis, mitochondrial respiratory chain, age-related diseases, retinopathy, oxidative stress, Podospora anserina, Ceriodaphnia affinis, Drosophila, mice, lipoprotein oxidation
MeSH terms
Aging, Animals, Antioxidants, Chloroplasts, Electron Transport, Fibroblasts, Humans, Mitochondria, Mitochondria, Heart, Oxidation-Reduction, Plastoquinone, Ubiquinone, Oxidants, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review