What the FOXO (part 1)

So I’m sure you’ve made the connection my brand name ‘Foxo Health’ and longevity. Along with Foxo’s association to longevity, I picked the name ‘Foxo Health’ because it is easy to remember, easy to spell and the dot com was available!

I’ve talked about the amazing properties of FOXO3 at high level in previous posts but I thought it about time to go a little deeper into the world of Foxo…here goes…

Firstly, let’s put aside FOX-O. Let’s start with the Fox. FOX proteins are a family of transcriptional regulators. They regulate the transcription or conversion of DNA to RNA (the first step in gene expression) and are therefore in essence orchestrating gene activity.

Why are they called FOX? Interestingly, the F comes the founding member of the family called the forkhead gene, named so because its mutation caused fruit flies to have a fork shaped head structure. The OX comes from a specialised group of genes called BOX.


As you may have guessed by now, FOXO proteins are not the only family members, but we also have FOXO-A and FOXO-B. In fact, the family ranges from FOXA all the way to FOXS.

The FOXO class are, to me, the real deal, as they orchestrate programmes of genes expression that regulate things like..

Cellular replication
Cell cycle arrest
DNA damage repair
Detoxification of reactive oxidative species


…and that’s just to name a few! There are four known FOXO genes in mammals with include FOXO1, FOXO3, FOXO4 and FOXO6. What happened to 2 and 5? FOXO2 turns out to be the same as FOXO3, and FOXO 5 is the fish version of FOXO3.

So in summary, the FOXO proteins are transcriptional regulators, they bind to certain regions of DNA and orchestrate programmes of gene expression – in particular those related to stress response.  In part two of this post, I will talk about how FOXO responds to the environment and some of the pathways that activate it.