Resveratrol Improves Mitochondrial Function and Protects against
Metabolic Disease by Activating SIRT1 and PGC-1α
Cell, Vol 127, 1109-1122, 15 December 2006
Marie Lagouge,8,1 Carmen Argmann,8,1 Zachary Gerhart-Hines,2 Hamid
Meziane,3 Carles Lerin,2 Frederic Daussin,4 Nadia Messadeq,3 Jill
Milne,5 Philip Lambert,5 Peter Elliott,5 Bernard Geny,4 Markku Laakso,6
Pere Puigserver,2 and Johan Auwerx1,3,7,∗
1 Institut de Génétique et de Biologie Moléculaire et Cellulaire,
CNRS / INSERM / ULP, 67404 Illkirch, France
2 Department of Cell Biology, John Hopkins University School of
Medicine, Baltimore, MD 21205, USA
3 Institut Clinique de la Souris, BP10142, 67404, Illkirch, France
4 Department of Respiratory, Cardiocirculatory and Exercise Physiology,
Hôpitaux Universitaires, 67000 Strasbourg, France
5 Sirtris Pharmaceutical, Cambridge, MA 02139, USA
6 Department of Medicine, University of Kuopio, 70211 Kuopio, Finland
7 IGBMC-ICS, 67404 Illkirch, France
∗Corresponding author
Johan Auwerx
[email hidden]
Diminished mitochondrial oxidative phosphorylation and aerobic capacity
are associated with reduced longevity. We tested whether resveratrol
(RSV), which is known to extend lifespan, impacts mitochondrial
function and metabolic homeostasis. Treatment of mice with RSV
significantly increased their aerobic capacity, as evidenced by their
increased running time and consumption of oxygen in muscle fibers.
RSV's effects were associated with an induction of genes for oxidative
phosphorylation and mitochondrial biogenesis and were largely explained
by an RSV-mediated decrease in PGC-1α acetylation and an increase
in PGC-1α activity. This mechanism is consistent with RSV being a
known activator of the protein deacetylase, SIRT1, and by the lack of
effect of RSV in SIRT1−/− MEFs. Importantly, RSV treatment
protected mice against diet-induced-obesity and insulin resistance.
These pharmacological effects of RSV combined with the association of
three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates
SIRT1 as a key regulator of energy and metabolic homeostasis.
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