Senescent cells (credits for the photo to Shutterstock)

Using FOXO4-DRI to eradicate senescent cells

Nina Khera
Feb 3, 2019 · 5 min read

One in 10 people over 65 will get dementia. That’s 10% of senior citizens finding out they have a destructive disease caused by deterioration of the body due to aging. Isn’t that insane? But have you ever wondered why?

Why do we age? That’s an awfully vague question, as there are so many factors playing into the process of aging. One of the biggest reasons is cellular senescence. Cellular senescence is a process initiated when your telomeres ‘run out’.

When cells divide, they copy the DNA from their chromosomes. Unfortunately, this process is very flawed and cuts off a bit of DNA at the end (insert dramatic gasp). Don’t worry, the body comes to our rescue with telomeres at the end of our chromosomes.

Telomeres and Cell Division (the process) Credits to http://canacopegdl.com/keyword/telomere-aging.html

Telomeres are kind of like the aglets on the ends of our shoelaces, except they slowly deteriorate. They’re dispensable DNA and a little bit more of them is cut off each cell division (they can typically withstand 50 to 70 divisions). When the telomeres ‘run out’, they send telomeric signals, turning the once healthy cells into senescent cells.

Senescent cells are undead cells (that should be dead) that are lacking a protein that tells them when to die. They’re one of the main reasons we age.

Think of your body as a machine, with senescent cells as the rust that prevents them from functioning. Many people dedicate their lives to finding ways to eradicate them, and researchers have gotten pretty far.

Historically, there has never been a perfect way to eradicate senescent cells. There might not ever be, that’s the reality of it. However, improvements are continuing to be made, so maybe someday there will be. At the moment, there are near perfect ways, this being one of them.

The treatment used is called FOXO4-DRI. Now, yes, for those of you who recognized the name of the peptide mentioned in my article title, this has been tested on mice. (as I talked about in one of my previous articles, ‘How to make mice live longer’)

FOXO4

I mentioned that it might be unsafe, but that was before I found out that it has been tested on humans as well as mice.

A team of researchers worked on an experiment titled ‘Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging’. They used FOXO4-DRI as a peptide to limit interactions with the gene found in senescent cells called p53 and FOXO4 to cause the death of senescent cells.

It’s found to decrease our bio-ages (biological age, what age you are in terms of health), and as a result to increase and restore the inner stability of our tissues.

Buck Institute for Research on Aging has obtained a patent for its usage in cancerous and senescent cells in an experiment titled ‘Targeting senescent and cancer cells for selective killing by interference with foxo4’.

foxo4-dri’s relation with senescent cells and its effects on mice (credits to https://molecularaging.com/2017/08/28/foxo4-dri-senolytic-peptide/)

This diagram shows FOXO4 being touched by FOXO4-DRI to avoid interacting with the p53 gene. It, as a result, initiates apoptosis in senescent cells. Over some time, the mice in this diagram became more healthy because of the drop in senescent cells.

So, what is FOXO4-DRI? That question has a simple answer. FOXO4-DRI is a senolytic. The name is derived from senescence and lytic (to destroy) They’re treatments under research to see if they can cause the death of senescent cells without killing the healthy ones in the process.

This might just be a miracle senolytic. Although, before you draw any conclusions, let me explain how this works.

FOXO4-DRI is pretty much a peptide (short chains of compounds part of the amino group linked by peptide bonds) that is injected into your body. It then finds the gene FOXO4 (short for forkhead box O4) and interacts with it to stop any communication with the p53 gene, initiating apoptosis (the destruction of cells) in senescent cells.

A peptide (bonded by the visible peptide bonds, with visible amino compounds) Credits to https://breakingmuscle.com/fitness/a-primer-on-peptides-what-they-are-and-why-to-take-them

To clarify, the FOXO4 gene is a gene that is involved in negative regulation of the cell cycle. The p53 gene is a gene that codes for a cell cycle regulating protein and helps with tumor suppressing functions.

Getting FOXO4-DRI to separate FOXO4 and p53 would decrease the number of senescent cells you gain.

FOXO4-DRI is the most effective and reliable senolytic currently being researched. It has the potential to do amazing good to those who want to live healthier and disease free lives (everyone). Maybe, with this, 10% of seniors wouldn’t get dementia. Could we reduce this to 1%? 0.1%? This could be possible with FOXO4-DRI.

A friend asked me a while ago, ‘You’re doing all this research with longevity and finding ways to live longer, so do you want to live forever?’. I know you may be expecting some epic philosophical answer, but the truth is, I had none.

I didn’t know what to say, but after thinking about it for a while, I have an answer. I don’t necessarily want to live forever, as there are so many downsides, but that doesn’t mean I don’t want to combat aging-related diseases.

This isn’t just about living forever, it’s about living healthily and illness-free. A good life doesn’t necessarily equal a long one, and I hope that isn’t what you took away. It’s quality over quantity.

If you could take away anything from this article, what would I want you to take away?

  • Senolytics are treatments under research to see if they can cause the death of senescent cells without killing the healthy ones in the process.
  • FOXO4-DRI is an effective senolytic and is a peptide that interacts with FOXO4 to stop any communication with the p53 gene, initiating apoptosis in senescent cells.
  • This could help us lead a disease and illness free life, by reducing our production of senescent cells.

Thank you for reading this article and be sure to give it some claps! I hope you liked it, and if you did, please share it with others who might like it as well!

Nina Khera

Written by

Nina Khera is a 13-year-old longevity researcher. She specializes in senescent cells & their eradication and is a co-founder of http://bioteinresearch.ca.

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