The paper:
M. Lagouge et al., "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α," Cell, 127:1109-22, 2006. (Cited in 139 papers)
The finding:
In 2006, Johan Auwerx of the Institute of Genetics and Molecular and Cellular Biology in France and colleagues treated mice with resveratrol (RSV), a natural plant compound known to extend lifespan in yeast, in order to test its impact on metabolism. RSV-fed mice, even on a high-fat diet, had increased muscle strength and longer running times than control mice. Not only were they resistant to diet-induced obesity, the RSV mice had lower body weights than normal-fed mice.
The mechanism:
While RSV had been known to activate the metabolic regulator SIRT1 in vitro, the Hot Paper proved it had similar effects in mice. Additionally, it showed that RSV also activates PGC-1α, a transcription coactivator known to...
The hunt:
Because RSV influences more pathways than just SIRT1, scientists have been on the hunt for specific SIRT1 activators. In 2007, Sinclair and colleagues found over 3,500 small molecule activators exclusive to SIRT1, structurally unrelated to resveratrol and 1,000 times more potent.
The future:
RSV is already being used to treat type II diabetics in clinical trials, as it has been shown to prevent insulin resistance. Currently, researchers are investigating the therapeutic potential of SIRT1 activators by testing them in animal models for various diseases associated with metabolism and aging.
| Average distance run at exhaustion (in meters): | |
| Chow diet mice: | 1,100m |
| Chow +RSV diet mice: | 2,000m |
| High-fat diet mice: | 900m |
| High-fat +RSV diet mice: | 1,700m |
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