Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts.
Open accessAbstract
Limitation of lifespan in replicative senescence is related to oxidative stress, which is probably both the cause and consequence of impaired mitochondrial respiratory function. The respiration of senescent human diploid fibroblasts was analysed by highresolution respirometry. To rule out cell-cycle effects, proliferating and growth-arrested young fibroblasts were used as controls. Uncoupled respiration, as normalized to citrate synthase activity, remained unchanged, reflecting a constant capacity of the respiratory chain. Oligomycin-inhibited respiration, however, was significantly increased in mitochondria of senescent cells, indicating a lower coupling of electron transport with phosphorylation. In contrast, growth-arrested young fibroblasts exhibited a higher coupling state compared with proliferating controls. In intact cells, partial uncoupling may lead to either decreased oxidative ATP production or a compensatory increase in routine respiration. To distinguish between these alternatives, we subtracted oligomycin-inhibited respiration from routine respiration, which allowed us to determine the part of respiratory activity coupled with ATP production. Despite substantial differences in the respiratory control ratio, ranging from 4 to 11 in the different experimental groups, a fixed proportion of respiratory capacity was maintained for coupled oxidative phosphorylation in all the experimental groups. This finding indicates that the senescent cells fully compensate for increased proton leakage by enhanced electron-transport activity in the routine state. These results provide a new insight into age-associated defects in mitochondrial function and compensatory mechanisms in intact cells.
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Senescent cells exhibit an increase in oxygen consumption rate.
“Evidence from the literature indicates that senescent cells exhibit an increase in oxygen consumption rate (Hutter et al., 2004; Son et al., 2017; Miwa et al., 2022; Bang et al., 2023; Diniz et al., 2024a).”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Hutter et al., 2004
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Aging promotes an increase in mitochondrial fragmentation in astrocytes
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- Authors
- HUTTER, E., RENNER, K., PFISTER, G., STÖCKL, P., JANSEN-DÜRR, P., & GNAIGER, E.
- Affiliations
- Abteilung Molekular-und Zellbiologie, Institut für Biomedizinische Alternsforschung der Österreichischen Akademie der Wissenschaften, Rennweg 10, A-6020 Innsbruck, Austria
- Universität Innsbruck (AT)
- Austrian Academy of Sciences (AT)
- Innsbruck Medical University (AT)
- Corresponding author
- PFISTER, Gerald
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2004-06-15
- Volume
- 380
- Issue
- 3
- Pages
- 919-928
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1224220
- OpenAlex
- W1980515769
- Cited by
- 235
- References
- 3
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 12 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 14 · 2017: 6 · 2016: 11 · 2015: 17 · 2014: 14 · 2013: 18 · 2012: 14
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Austrian Science Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- replicative senescence, mitochondrial respiration, oxidative phosphorylation, human diploid fibroblasts, respiratory control ratio, uncoupled respiration, electron transport, proton leak, oxidative stress, aging, compensatory mechanisms
- MeSH terms
- Aging, Cell Count, Cell Line, Citrate (si)-Synthase, Fibroblasts, Humans, L-Lactate Dehydrogenase, Membrane Potentials, Mitochondria, Oxidative Phosphorylation, Cell Respiration
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