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| Status |
Public on Aug 21, 2017 |
| Title |
Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway. |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by array
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| Summary |
Aging is a major international concern and brings with it formidable socioeconomical and healthcare challenges. An attainable approach to improve general health in humans is using small molecules. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits aging-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in the aging animal model C. elegans, which shares many major longevity pathways with those of mammals. Tomatidine improves behaviors related to healthspan, including increased pharyngeal pumping and swimming movement, and also reduces deterioration of muscle cells in worms. Microarray, imaging, and behavioral analysis reveal that tomatidine maintains mitochondrial homeostasis through mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the cellular antioxidant response SKN-1/Nrf2 pathway, followed by increased mitophagy in worms, 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 towards diseases of aging.
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| Overall design |
N2 worms from L4 stage were exposed to either vehicle (DMSO) or 25 μM tomatidine, and four independent experiments for each condition were collected on adult Day 7.
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| Contributor(s) |
Fang EF, Waltz TB, Kassahun H, Lu Q, Kerr JS, Morevati M, Fivenson EM, Wollman BN, Marosi K, Wilson MA, Iser WB, Eckley DM, Zhang Y, Lehrmann E, Goldberg IG, Scheibye-Knudsen M, Mattson MP, Nilsen H, Bohr VA, Becker KG |
| Citation(s) |
28397803 |
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| Submission date |
Aug 05, 2016 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL10094 |
Agilent-020186 C. elegans (V2) Gene Expression Microarray (Feature Number version) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA337916 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85237_RAW.tar |
21.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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