Tomatidine Enhances Lifespan and Healthspan in C. elegans through Mitophagy Induction Via the SKN-1/Nrf2 Pathway
Open accessAbstract
Aging is a major international concern that brings formidable socioeconomic and healthcare challenges. Small molecules capable of improving the health of older individuals are being explored. Small molecules that enhance cellular stress resistance are a promising avenue to alleviate declines seen in human aging. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in C. elegans, an animal model of aging which shares many major longevity pathways with mammals. Tomatidine improves many C. elegans behaviors related to healthspan and muscle health, including increased pharyngeal pumping, swimming movement, and reduced percentage of severely damaged muscle cells. Microarray, imaging, and behavioral analyses reveal that tomatidine maintains mitochondrial homeostasis by modulating mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the SKN-1/Nrf2 pathway and possibly other cellular antioxidant response pathways, followed by increased mitophagy. This mechanism occurs in C. elegans, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions for diseases of aging.
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Exposure to mitophagy modulators increases lifespan in worms.
“exposure to mitophagy modulators increases lifespan in worms23,24.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [23]
Tomatidine prolongs lifespan and health span in C. elegans by stimulating mitophagy.
“and to prolong lifespan and health span in C. elegans by stimulating mitophagy [163]”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [163]
Tomatidine improves muscle function during aging in C. elegans by activating the Nrf2/Protein skinhead-1 pathway and upregulating mitophagy and antioxidant cellular defenses.
“Besides, it improves muscle function during aging in C. elegans by activating the Nrf2/Protein skinhead-1 pathway and upregulating mitophagy and antioxidant cellular defenses [137].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [137]
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- Authors
- Fang, E. F., Waltz, T. B., Kassahun, H., Lu, Q., Kerr, J. S., Morevati, M., Fivenson, E. M., Wollman, B. N., Marosi, K., Wilson, M. A., Iser, W. B., Eckley, D. M., Zhang, Y., Lehrmann, E., Goldberg, I. G., Scheibye-Knudsen, M., Mattson, M. P., Nilsen, H., Bohr, V. A., & Becker, K. G.
- Affiliations
- National Institutes of Health (US)
- University of Copenhagen (DK)
- University of Oslo (NO)
- Corresponding author
- Bohr, Vilhelm A.
- Becker, Kevin G.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-04-11
- Volume
- 7
- Issue
- 1
- Pages
- 46208-46208
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5387417
- OpenAlex
- W2606837944
- Cited by
- 187
- References
- 66
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 25 · 2023: 24 · 2022: 30 · 2021: 25 · 2020: 22 · 2019: 18 · 2018: 12 · 2017: 6
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- National Institute on Aging
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- tomatidine, lifespan extension, healthspan, aging, mitophagy, mitochondrial biogenesis, reactive oxygen species, mitochondrial homeostasis, skeletal muscle atrophy, Caenorhabditis elegans, neuroprotection
- MeSH terms
- Animals, Organelle Biogenesis, DNA-Binding Proteins, Gene Expression Regulation, Longevity, Mitochondria, Muscles, Stress, Physiological, Tomatine, Transcription Factors, Signal Transduction, Caenorhabditis elegans, Reactive Oxygen Species, Caenorhabditis elegans Proteins, NF-E2-Related Factor 2, Transcriptome, Mitophagy
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