PMID: 18239138Circ Res. 2008 Mar 28;102(6):703-10. Epub 2008 Jan 31.
Sirt7 increases stress resistance of cardiomyocytes and prevents
apoptosis and inflammatory cardiomyopathy in mice.Vakhrusheva O,
Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T, Bober E.
Max-Planck-Institute for Heart and Lung Research, Department of
Cardiac Development and Remodelling, Bad Nauheim, Germany.
Sirt7 is a member of the mammalian sirtuin family consisting of 7
genes, Sirt1 to Sirt7, which all share a homology to the founding
family member, the yeast Sir2 gene. Most sirtuins are supposed to act
as histone/protein deacetylases, which use oxidized NAD in a sirtuin-
specific, 2-step deacetylation reaction. To begin to decipher the
biological role of Sirt7, we inactivated the Sirt7 gene in mice. Sirt7-
deficient animals undergo a reduction in mean and maximum lifespans
and develop heart hypertrophy and inflammatory cardiomyopathy. Sirt7
mutant hearts are also characterized by an extensive fibrosis, which
leads to a 3-fold increase in collagen III accumulation. We found that
Sirt7 interacts with p53 and efficiently deacetylates p53 in vitro,
which corresponds to hyperacetylation of p53 in vivo and an increased
rate of apoptosis in the myocardium of mutant mice. Sirt7-deficient
primary cardiomyocytes show a approximately 200% increase in basal
apoptosis and a significantly diminished resistance to oxidative and
genotoxic stress suggesting a critical role of Sirt7 in the regulation
of stress responses and cell death in the heart. We propose that
enhanced activation of p53 by lack of Sirt7-mediated deacetylation
contributes to the heart phenotype of Sirt7 mutant mice.
Resveratrol does activate Sirt7, and so may help prevent cardiomyopathy and some forms of congestive heart failure. A research cardiologist I correspond with is very interested in these results. We may see results from human trials in the not too distant future.
