How to stay young by activating the longevity gene, Foxo3

In this blog, I’m going to talk about an amazing genetic pathway or gene in the body called FOXO3, how it’s been linked to long life, and what we can do to increase its activation.

So FOXO3 is a genetic pathway we all have that’s really special when it comes to dealing with stress to the body.  It’s often referred to as the ‘longevity gene’. As with the majority of genes, it is either turned on or turned off at any given time.  When we turn on a gene, that gene is said to be ‘expressed.’ If the gene is turned off, it’s still there but it’s just not doing anything.  

There are some humans that have a variation in the FOXO3 gene which results in them expressing or activating this gene more often.  Those that have this variation or polymorphism are said to have a 2.7 fold increased likelihood of living to be 100 years old. Living to be a 100 is when you become what’s called a ‘centenarian’.  

Also, an interesting little study showed that genetically engineered worms who had their FOXO3 gene permanently turned on, lived 50 to 100% longer, so they doubled their lifespans in some cases. Of course, humans are not worms but it’s an interesting study.

So what’s going on here, why is FOXO3 associated to longer life?  Well it turns out that FOXO3 is a like a master regulator of a whole raft of other genes which are brilliant at healing and protecting our bodies. So here are 5 things that the FOXO3 pathway is believed to do by orchestrating all these other genes –

  1. Activates genes that are involved in repairing DNA damage – both mitochondrial and nuclear
  2. Acitivates antioxidant genes which can help to prevent DNA damage
  3. It activates an autophagic pathway, and autophagy is basically the clearing away of damaged senescent cells that are non functional that can sit around and secrete harmful substances
  4. It activates genes that play a part in the immune system.  I’ve talked about the immune system before and how it can fight off virus and infections but also kill off pre cancer cells
  5. It also regulates genes that involved in stem cell function, increasing their division and growth.  That’s really important because as we age, we lose our stem cell function, and stem cells are important for helping us to replenish various cell populations in different tissues in the body.  If we can’t replenish then it can lead to organ dysfunction.

Those are some pretty awesome things that the FOXO3 pathway can do which may explain why increasing its activation is linked to longevity.  

The question is how can we increase expression of FOXO3?  Well I’m going to talk about 4 ways that we can do it.

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Number 1 is exercise.  So FOXO3 expression is increased when we exercise.  So we all know that exercising is good for us but the increased activation in FOXO3 activation is like the icing on the cake.  So whether it’s running, dancing, biking or lifting weights; exercising will increase FOXO3.

Number 2 is heat stress.  How do we get heat stress?  The easiest way is to get in a sauna and sweat.  So using a sauna will also increase FOXO3 expression.


Number 3 is by being in ketosis.  I talk about ketosis a lot so if you want to know more, please check out some of my other blogs.   Ketosis is basically a metabolic state where we burn fat as our primary fuel source rather than sugar.  Now when we do this, the body produces something called ketones, one of which is called Beta Hydroxybutyrate.  It turns out that this ketone body BHB increases the expression of FOXO3.

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The last way to increase FOXO3 expression is an easy one, and that’s drinking green tea.  Green tea is rich in something called polyphenols, the most abundant of which is one called Epigallocatechin 3-gallate or EGCE, and its the EGCE which increases the expression of FOXO3.  So, the fourth way is to drink green tea!

So there you have it, those are four ways to increase the expression of FOXO3.  So I’ll do a quick recap now to wrap up the blog.

FOXO3 gene or pathway is often referred to as the ‘longevity gene’ and people who have a genetic variation of this gene and express it more have  a 2.7 fold increased chance of living to be 100. The FOXO3 pathway is a master regulators of a raft of genes, so its activation increases DNA damage repair genes, antioxidant genes, it activates an autophagy pathway to clear away damaged senescent cells, it activates genes involved in the immune system and it regulates genes involved in stem cell function.

How do we increase activation of FOXO3?  Number 1, we can exercise, number 2, we can use a sauna, number 3, we can get into ketosis or fat burning mode and number 4 we can drink green tea.  Oh, we can also eat wild salmon but I’ll have to write more about that in another blog!

To learn more about FOXO proteins, read my article FOXO transcription factors