SIRT7 - villain or key to longevity?

I am following up on a previous post in which a study indicating the possibility of heart damage with a ketogenic diet was mentioned. The result of the search for the cause was the finding that the ketogenic diet reduces the activity of histone deacetylase 2 (HDAC2), which controls the deacetylase SIRT7. So SIRT7 is activated, which is supposed to be the problem.

I did some googling and found that SIRT7 activation seems to be generally very good. For example, it suppresses (pseudo)hypoxia, i.e. chronic inflammation. I found a number of studies that consider the activation of SIRT7 to be very beneficial, they are looking for different drugs that would activate SIRT7, but they do not tell us that it is β-hydroxybutyrate or even the short-chain fatty acids acetate/vinegar and butyrate that activate SIRT7 through HDAC2 suppression. All these substances are considered very beneficial. So we have a rather fundamental contradiction here. Does SIRT7 activation have positive or negative effects on health? I would preliminarily say that even good things should not be overdone. Any negative impact on the heart could be the result of too much activation of SIRT7, it's just probably a general rule of thumb that nothing should be overdone. Nor the positive effects of SIRT7 activation. It is better to have stable and low levels permanently 24/7, simply in the style of "being available", than to have a significant increase in the level of β-hydroxybutyrate or short-chain fatty acids for one hour and not have them in the blood at all for the rest of the day. It is therefore possible to assume that short-term high levels can be harmful.

Let's look now at one study that promises us longevity mediated by the activation of SIRT7 deacetylase.

SIRT7 acts against many types of stress, such as injury or inflammation. Supports tissue healing.

There are many areas where SIRT7 has a positive effect

  • defense against lifelong stresses of any origin (bad metabolism, inflammation, cancer, etc.) 

  • protection against cardiovascular, kidney, lung and neurodegenerative diseases

  • works against infertility

  • works against cancer

Aging causes SIRT7 activity to decrease, but its level can be restored to suppress aging.


SIRT7 also acts against cancer.

Overall, SIRT7 acts as a molecular protector and could slow down aging, although there are sometimes conflicting results that will still need to be clarified, especially for use in humans. So far, studies have only been conducted on animals, and the question is whether the results can also be applied to humans. It may also be questionable whether the reduction of HDAC2 activity is the optimal way to activate SIRT7, we know that acetate may use a slightly different way by activating ACSS2 and AMPK and directly activates SIRT7 by phosphorylation.

Lack of glucose (but also vinegar/acetate, my note) activates AMPK, which phosphorylates SIRT7, which regulates gluconeogenesis depending on the time of day.


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References:

SIRT7: the seventh key to unlocking the mystery of aging

SIRT7 in the aging process

Sirtuin-7 Inhibits the Activity of Hypoxia-inducible Factors

SCFAs Ameliorate Chronic Postsurgical Pain–Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats

 

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