Journal
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 98, Issue 20, Pages 8617-8628Publisher
SPRINGER
DOI: 10.1007/s00253-014-5890-5
Keywords
Chronological lifespan; Cryptotanshinone; Amino acid; Tor1/Sch9/Gcn2/Sod2; Nutrient-sensing pathway; Conserved longevity mechanism
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Funding
- National University of Singapore Virtual Institute for the Study of Aging (VISA) [R-143-000-437-290]
- National University of Singapore (Suzhou) Research Institute [NUSRI-2011-007]
- Industrialization-Academia-Research Platform Grant of Jiangsu Province, China
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Natural products with anti-aging property have drawn great attention recently but examples of such compounds are exceedingly scarce. By applying a high-throughput assay based on yeast chronological lifespan measurement, we screened the anti-aging activity of 144 botanical materials and found that dried roots of Salvia miltiorrhiza Bunge have significant anti-aging activity. Tanshinones isolated from the plant including cryptotanshione, tanshinone I, and tanshinone IIa, are the active components. Among them, cryptotanshinone can greatly extend the budding yeast Saccharomyces cerevisiae chronological lifespan (up to 2.5 times) in a dose- and the-time-of-addition-dependent manner at nanomolar concentrations without disruption of cell growth. We demonstrate that cryptotanshinone prolong chronological lifespan via a nutrient-dependent regime, especially essential amino acid sensing, and three conserved protein kinases Tor1, Sch9, and Gcn2 are required for cryptotanshinone-induced lifespan extension. In addition, cryptotanshinone significantly increases the lifespan of SOD2-deleted mutants. Altogether, those data suggest that cryptotanshinone might be involved in the regulation of, Tor1, Sch9, Gcn2, and Sod2, these highly conserved longevity proteins modulated by nutrients from yeast to humans.
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