Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration during aging.
Open accessAbstract
Summary: Replicative and chronological lifespan are two different modes of cellular aging. Chronological lifespan is defined as the duration during which quiescent normal cells retain their capacity to re‐enter the proliferative cycle. This study investigated whether changes in metabolism occur during aging of quiescent normal human fibroblasts ( NHF s) and the mechanisms that regulate these changes. Bioenergetics measurements were taken in quiescent NHF s from younger (newborn, 3‐day, 5‐month, and 1‐year) and older (58‐, 61‐, 63‐, 68‐, and 70‐year) healthy donors as well as NHF s from the same individual at different ages (29, 36, and 46 years). Results show significant changes in cellular metabolism during aging of quiescent NHF s: Old NHF s exhibit a significant decrease in glycolytic flux and lactate levels, and increase in oxygen consumption rate ( OCR ) and ATP levels compared to young NHF s. Results from the Seahorse XF Cell Mito Stress Test show that old NHF s with a lower Bioenergetic Health Index ( BHI ) are more prone to oxidative stress compared to young NHF s with a higher BHI . The increase in OCR in old NHF s is associated with a shift in mitochondrial dynamics more toward fusion. Genetic knockdown of mitofusin 1 ( MFN 1) and optic atrophy 1 ( OPA 1) in old NHF s decreased OCR and shifted metabolism more toward glycolysis. Downregulation of MFN 1 and OPA 1 also suppressed the radiation‐induced increase in doubling time of NHF s. In summary, results show that a metabolic shift from glycolysis in young to mitochondrial respiration in old NHF s occurs during chronological lifespan, and MFN 1 and OPA 1 regulate this process.
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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 Son et al., 2017
The Results section, “Cellular metabolism shifts from glycolysis to mitochondrial respiration during aging of normal human fibroblasts,” reports higher oxygen consumption in older than younger quiescent fibroblasts. It also reports no significant difference in senescence markers between those groups, so the finding does not establish increased oxygen consumption in senescent cells. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGenetic knockdown of MFN1 and OPA1 in old normal human fibroblasts decreased the oxygen consumption rate and shifted metabolism toward glycolysis.
“Genetic knockdown of MFN1 and OPA1 in old normal human fibroblasts decreased the oxygen consumption rate and shifted metabolism toward glycolysis.”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Son et al., 2017
The increase in oxygen consumption rate in aged normal human fibroblasts is associated with a shift in mitochondrial dynamics toward fusion.
“The increase in oxygen consumption rate in aged normal human fibroblasts is associated with a shift in mitochondrial dynamics toward fusion.”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Son et al., 2017
Downregulation of MFN1 and OPA1 also suppressed the radiation-induced increase in doubling time of human fibroblasts.
“Downregulation of MFN1 and OPA1 also suppressed the radiation-induced increase in doubling time of human fibroblasts (Son et al., 2017).”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Son et al., 2017
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- Authors
- Son, J. M., Sarsour, E. H., Kakkerla Balaraju, A., Fussell, J., Kalen, A. L., Wagner, B. A., Buettner, G. R., & Goswami, P. C.
- Affiliations
- University of Iowa (US)
- Free Radical and Radiation Biology Division Department of Radiation Oncology University of Iowa Iowa City IA USA
- Corresponding author
- Goswami, Prabhat C.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2017-07-31
- Volume
- 16
- Issue
- 5
- Pages
- 1136-1145
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5595680
- OpenAlex
- W2739725666
- Cited by
- 71
- References
- 9
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 6
- FWCI
- 2.01
- 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
- National Institutes of Health (2R01‐CA111365, CA169046, P30 CA086862)
- Holden Comprehensive Cancer Center, University of Iowa
- 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
- mitofusin 1, optic atrophy 1, mitochondrial dynamics, mitochondrial fusion, chronological aging, cellular metabolism, glycolysis, mitochondrial respiration, oxygen consumption rate, oxidative stress, human fibroblasts, radiation-induced cell proliferation, gene knockdown
- MeSH terms
- Adult, Aged, Aging, Cell Division, Cells, Cultured, Fibroblasts, Gene Expression Regulation, Glycolysis, Humans, Infant, Infant, Newborn, Middle Aged, Mitochondria, Oxidative Phosphorylation, Oxygen Consumption, Signal Transduction, Cell Respiration, GTP Phosphohydrolases, Mitochondrial Membrane Transport Proteins, RNA, Small Interfering, Mitochondrial Dynamics
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