Antiaging properties of a grape-derived antioxidant are regulated by mitochondrial balance of fusion and fission leading to mitophagy triggered by a signaling network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN
Open accessAbstract
It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R) in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.
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Lifespan extension in response to resveratrol supplementation in rats is associated with activation of the Pink1/Parkin pathway.
“It was also reported that lifespan extension in response to resveratrol supplementation in rats was associated with an activation of the Pink1/Parkin pathway [164].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [164]
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- Authors
- Das, S., Mitrovsky, G., Vasanthi, H. R., & Das, D. K.
- Affiliations
- Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT, USA
- University of Debrecen (HU)
- Pondicherry University (IN)
- University of Connecticut (US)
- Corresponding author
- Das, Dipak K.
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-13
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC3942197
- OpenAlex
- W2110795504
- Cited by
- 173
- References
- 44
- Citations by year
- 2026: 3 · 2024: 14 · 2023: 16 · 2022: 28 · 2021: 26 · 2020: 20 · 2019: 13 · 2018: 16 · 2017: 13 · 2016: 13 · 2015: 7 · 2014: 3
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2022-08-13)
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (HL 33889, HL 22559, HL 34360)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- resveratrol, SIRT1, SIRT3, FOXO3, PINK1, Parkin, mitophagy, mitochondrial fission and fusion, ischemia-reperfusion injury, cardioprotection, anti-aging, glutathione, caloric restriction mimetics, longevity
- MeSH terms
- Forkhead Box Protein O3, Resveratrol, PTEN-Induced Putative Kinase, Aging, Animals, Antioxidants, Fluorescent Antibody Technique, Glutathione, Heart Ventricles, Male, Myocardial Infarction, Myocardium, Protein Kinases, Stilbenes, Blotting, Western, Signal Transduction, Myocardial Ischemia, Rats, Sprague-Dawley, Apoptosis, Reactive Oxygen Species, Vitis, Myocytes, Cardiac, Sirtuins, Intracellular Space, Ubiquitin-Protein Ligases, Rats, Forkhead Transcription Factors, Mitochondrial Dynamics, Mitophagy, In Vitro Techniques
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