Honokiol increases SIRT3 levels and stops cardiac hypertrophy in mice

In an expansive study, researchers found that Honokiol increases levels of SIRT3. This appears to be the first ever report describing a pharmacological activator of Sirt3. Exercise and calorie restriction are the only other known methods to increase SIRT3.

Sirtuins in general are believed to extend lifespan across species, although the role in nematodes and fruitflies is controversial. Whether sirtuins can truly and broadly reverse aging-associated degeneration is unknown but there are increasing scientific results showing health benefits and improvements. In this recent SIRT3 focused study the findings suggest that bolstering mitochondrial function and cell stress resistance by increasing SIRT3 levels may offer a promising therapeutic target for protecting against age-related cognitive decline and brain diseases. This study found that SIRT3 reverses aging-associated degeneration in mice.

It is known that SIRT3 is suppressed with aging and therefore finding compounds that can offset this decline may be a promising approach to fend off some aspects of age related degeneration.


In the study it was demonstrated that honokiol is firstly present in the mitochondria and secondly enhances SIRT3 expression nearly two-fold. There was also indication that honokiol binds to SIRT3 changing the properties in a way that further increase its activity. The figure on the left shows the schematic pathways of SIRT3 increase effect by honokiol.

It should be noted that the near two fold increase was observed with in-vitro testing. In-vivo testing in mice showed that supplementation with honokiol increased SIRT3 levels in mice with an induced cardiac hypertrophy. Compared to a control group of similar mice without supplementation the SIRT3 levels were markedly higher.

The increased SIRT3 activity was associated in the study with reduced acetylation of mitochondrial SIRT3 substrates, MnSOD and OSCP which stopped the development of cardiac hypertrophy.

Overall these results indicate that honokiol is capable of activating SIRT3 and having health benefits like the blocking of cardiac hypertrophic response in vivo.

The supplementation in the study was done by dissolving honokiol in peanut oil which was injected at a rate of 0.2mg/kg/day intraperitoneally. Therefore it is not easily possible to make translations to human doses.


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