Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity
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Summary: Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain. These changes are accompanied by a decrease in cyclophilin D activity and acetylation and an increase in Sirt3 expression. This suggests that Sirt3‐mediated deacetylation and inhibition of cyclophilin D in CR promote the inhibition of mitochondrial permeability transition, resulting in enhanced mitochondrial calcium retention. Altogether, our results indicate that enhanced mitochondrial calcium retention capacity underlies the beneficial effects of CR against excitotoxic conditions. This protection may explain the many beneficial effects of CR in the aging brain.
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SIRT3 attenuates cell death after excitotoxic stress and mediates the protective effect of exercise against such stress, possibly via deacetylation of cyclophilin D.
“Similarly, SIRT3 function has been shown to attenuate cell death after excitotoxic stress, and mediates the protective effect of exercise against such stress ((Cheng et al. 2016)), possibly via deacetylation of cyclophilin D ((Cheng et al. 2016),(Amigo et al. 2017)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Amigo et al. 2017
Many protective features of the calorie-restriction response, including resistance to oxidative stress and reduced hearing loss, require SIRT3.
“SIRT3 is required for many protective aspects of this adaptive shift ((Someya et al. 2010); (Qiu et al. 2010); (Amigo et al. 2017)), such as oxidative stress resistance and attenuated hearing loss.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Amigo et al. 2017
Dietary restriction prevents mPTP opening in liver and brain mitochondria but not in skeletal muscle or heart.
“Several studies demonstrated that dietary restriction prevents mPTP opening in liver and brain mitochondria [293,294,295], but not in the skeletal muscle or heart [296].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [295]
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- Authors
- Amigo, I., Menezes‐Filho, S. L., Luévano‐Martínez, L. A., Chausse, B., & Kowaltowski, A. J.
- Affiliations
- Departamento de Bioquímica Instituto de Química Universidade de São Paulo São Paulo Brazil
- Universidade de São Paulo (BR)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2016-09-13
- Volume
- 16
- Issue
- 1
- Pages
- 73-81
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5242290
- OpenAlex
- W2519335189
- Cited by
- 95
- References
- 45
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 7 · 2019: 13 · 2018: 10 · 2017: 6 · 2016: 2
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/51906‐1)
- Instituto Nacional de Ciência e Tecnologia de Processos Redox em Biomedicina
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- caloric restriction, excitotoxicity, mitochondrial calcium retention capacity, brain mitochondria, mitochondrial permeability transition, cyclophilin D, SIRT3, acetylation, electron transport chain, antioxidant defense, calcium overload, neuroprotection, brain aging
- MeSH terms
- Peptidyl-Prolyl Isomerase F, Acetylation, Animals, Antioxidants, Brain, Calcium, Electron Transport, Male, Mitochondria, Neurotoxins, Cell Death, Rats, Sprague-Dawley, Neuroprotective Agents, Glutamic Acid, Cyclophilins, Caloric Restriction, Serum, Mice
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