Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians
Open accessAbstract
Mitochondria have been considered for long time as important determinants of cell aging because of their role in the production of reactive oxygen species. In this study we investigated the impact of mitochondrial metabolism and biology as determinants of successful aging in primary cultures of fibroblasts isolated from the skin of long living individuals (LLI) (about 100 years old) compared with those from young (about 27 years old) and old (about 75 years old) subjects. We observed that fibroblasts from LLI displayed significantly lower complex I-driven ATP synthesis and higher production of H2O2 in comparison with old subjects. Despite these changes, bioenergetics of these cells appeared to operate normally. This lack of functional consequences was likely due to a compensatory phenomenon at the level of mitochondria, which displayed a maintained supercomplexes organization and an increased mass. This appears to be due to a decreased mitophagy, induced by hyperfused, elongated mitochondria. The overall data indicate that longevity is characterized by a preserved bioenergetic function likely attained by a successful mitochondria remodeling that can compensate for functional defects through an increase in mass, i.e. a sort of mitochondrial "hypertrophy".
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Dermal fibroblasts from centenarians, but not from 70-year-old subjects, show compensated mitochondrial dysfunction with decreased complex I-driven ATP synthesis and increased H2O2 production.
“we have reported that dermal fibroblasts from centenarians but not from 70-year-old subjects display a compensated mitochondrial dysfunction, characterized by decreased complex I-driven ATP synthesis and increased H 2 0 2 production (34).”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [34]
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- Authors
- Sgarbi, G., Matarrese, P., Pinti, M., Lanzarini, C., Ascione, B., Gibellini, L., Dika, E., Patrizi, A., Tommasino, C., Capri, M., Cossarizza, A., Baracca, A., Lenaz, G., Solaini, G., Franceschi, C., Malorni, W., & Salvioli, S.
- Affiliations
- University of Bologna (IT)
- Istituto Superiore di Sanità (IT)
- University of Modena and Reggio Emilia (IT)
- Institute of Organic Synthesis and Photoreactivity (IT)
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2014-04-30
- Volume
- 6
- Issue
- 4
- Pages
- 296-310
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC4032796
- OpenAlex
- W2108525712
- Cited by
- 90
- References
- 64
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 6 · 2014: 1
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- Funders
- European Commission (FP7/2007-2011, FP7/2007, 259679)
- Ministero dell’Istruzione, dell’Università e della Ricerca (PON01_00937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- centenarians, mitochondrial hyperfusion, mitophagy, autophagy, cellular bioenergetics, successful aging, dermal fibroblasts, mitochondrial complex I, ATP production, hydrogen peroxide production, mitochondrial supercomplexes, mitochondrial hypertrophy, mitochondrial remodeling
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Autophagy, Cells, Cultured, Energy Metabolism, Female, Fibroblasts, Flow Cytometry, Fluorescent Antibody Technique, Humans, Male, Mitochondria, Blotting, Western
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