Wr
Scientists link gene that promotes long lifespan to
cholesterol.
MIT
researchers
have discovered a link between a gene believed to promote
long lifespan and a pathway that flushes
cholesterol from the body.
The
finding could help
researchers create drugs that lower the risk of
diseases associated with high cholesterol, including atherosclerosis
(clogged arteries) and Alzheimer’s disease.
The
study focused on a gene called SIRT1, which the researchers found
prevents cholesterol buildup by activating a cellular pathway that
expels cholesterol from the body via HDL (high density lipoprotein or
“good cholesterol”).
“SIRT1
is an important mediator of cholesterol efflux, and as such it’s
predicted to play a role in the development of age-associated diseases
where cholesterol is a contributing factor,” said Leonard Guarente, MIT
professor of biology and senior author of a paper on the work to be
published in the Oct. 12 issue of Molecular Cell.
Drugs
that enhance the effects of SIRT1 could lower the risk of
cholesterol-related diseases, Guarente said. Potential drugs could be
based on polyphenols, which are found in red wine and have been shown
to enhance SIRT1. However, the quantities naturally found in red wine
are not large enough to have a significant impact on cholesterol levels.
In
earlier studies, Guarente has shown that high levels of SIRT1 can be
achieved with extreme calorie restriction, but that is unappealing for
most people.
“If
you had a drug that could increase expression of SIRT1, that could
replicate the effects of calorie restriction,” Guarente said. “This is
not going to replace the need for a healthy lifestyle, but it’s a
supplement that could potentially make you healthier.”
SIRT1
is the mammalian homologue to SIR2, a gene that has been shown to slow
aging in yeast and roundworms. Researchers have been curious to find
out whether SIRT1 has similar effects.
In
the new MIT study, researchers found that low SIRT1 levels in mice lead
to cholesterol buildup in cells such as macrophages, a type of immune
cell, due to reduced activity of a protein called LXR (liver X
receptor).
LXR
is responsible for transporting cholesterol out of macrophage cells.
When full of cholesterol, the macrophages can generate plaques that
clog arteries. SIRT1 boosts LXR activity, so that cholesterol is
expelled from macrophages and out of the body by HDL.
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