SIRT-1 and Saving Your Brain

May 09, 2016

Sirt-1 and Saving Your Brain 

References:  PNAS 2013,  

We need three things to make it to healthy aging: our eyes, our knees and our brains. At the current rate, 50% of us are getting Alzheimer's if we get to age 85. Bummer. The means by which Alzheimer's Disease (AD) causes its havoc is gradually being understood. This reference might be one of the most seminal articles to show the way forward. Let me explain the details.

We know that AD is characterized by several processes. One is the brain shrinking, with loss of executive neurons in the front of the brain leading the way. Premature cell death of neurons is part of that. Another is a loss of connections between neurons. And finally, there is accumulation of abnormally formed amyloid proteins.

Enter the APOE-4 gene. It is now pretty well known that having two copies of the APOE-4 gene has risk of developing AD (on the order of 70-80%). Having even one copy confers a doubling of risk. The amyloid precursor protein (APP) can but chopped up into different end results, and that's what the APOE-4 gene does. It chops at a place that makes a different protein. 

This is where we introduce the SIRT-1 effect. SIRT-1 exists in balance with SIRT-2. SIRT-1 is the good stuff. SIRT-2 is not so good. SIRT-1 reduces the production of beta amyloid. And it's APOE-4 that lowers SIRT-1. Ha, that's how APOE-4 wreaks its havoc. With enough SIRT-1, you don't make beta-amyloid.

I don't mean to make this any more complicated than it has to be. And I'm not sure it's any better known than this right now, except for by the best of brain scientists. But the nitty - gritty is, we want to have more SIRT-1. If we can up regulate SIRT-1, we can counteract the nasty tendency of APOE-4 genes to make beta-amyloid accumulate in our brains.

How do we do that? What can we do to stimulate SIRT-1? That's the Holy Grail of medicine. Now, enter Resveretrol. The red stuff in red wine. Turns out it stimulates SIRT-1, and many other cellular functions. In fact, there is so much conflicting evidence about resveretrol's effects that we are only at the beginning of understanding the SIRT system and how it works. Guest what else stimulates SIRT-1? If increasing life span of brain cells is what resveratrol does, what do you think would be the most potent method of increasing mammal life span - and how does it work? The answer: calorie restriction, which markedly increases SIRT-1 activity.

WWW. What will work for me. I've taken resveratrol off and on for several years as a supplement. Hearing that Dale Bredesen uses it at UCLA in all of his Alzheimer's patients, with the specific target of increasing SIRT-1 activity suggests we may all be interested in it. So, I added it to my supplement list a couple of months back. I don't know how to measure it, except to take it on faith. We don't have a SIRT-1 test yet. It might be one of our most useful if we did.

Pop Quiz

1. SIRT-1 is a protein that prolongs life? T or F                    Answer. True

2. The Alzheimer's associated gene, APOE-3 lowers SIRT levels. T or F                      Answer:. False. The Alzheimer's associated gene is the APOE-4, and that does lower SIRT-1 levels.

3. Resveretrol raises SIRT-1 levels, thereby balancing out the tendency of the APOE-4 gene to cause trouble. T or F                             Answer:  Now we are true.

4. Resveretrol reliably increases human life span. T or F                            Answer:  Not so fast. It affects many cellular functions and its research conclusions are still far from certain. But it's brain effects seems pretty sure.

5. I should be on resveretrol if I want to preserve my brain.                      Answer:  That is the current best wisdom we have in a not-certain complex picture still being elucidated.

(Editor's Note:  This is the first of David Sinclair's discoveries.  Predating Metformin and NAD.  It's fun to follow the progression of his science.   Read his book: Lifespan.     Edited Nov 2021)