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Fisetin: The Anti-Aging Assassin

Plus: the healthy baked snacks that are tastier than French fries

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The 10almonds Team
April 29, 2024

Today’s almonds have been activated by:

❝I like to pretend I already died and asked God to send me back to Earth so I can swim in lakes gain and see mountains and get my heart broken and love my friends and cry so hard in the bathroom and go grocery shopping 1,000 more times. And that I promised I would never forget the miracle of being here.❞

⏰ IN A RUSH?

Today’s 30-Second Summary

If you don’t have time to read the whole email today, here are some key takeaways:

  • Fisetin is a flavonoid (specifically, a flavonol), but it’s a little different than most, having an extra anti-aging trick up its sleeve

    • Today’s main feature looks at fisetin’s expected and unexpected properties: yes, it’s an antioxidant, anti-inflammatory, anticancer agent… But it also selectively promotes cell death in aging cells (this is good for you), keeping your remaining cells (those that are getting copied forwards!) younger.

  • As we age, our collagen levels tend to get depleted more easily. Collagen is important not just for youthful good looks, but also for the health of bones and joints

    • Today’s sponsor NativePath are offering high-quality collagen without additives or harmful impurities

Read on to learn more about these things, or click here to visit our archive

🤫 A WORD TO THE WISE

Heartbeet

The humble beetroot can do a lot for blood-related health, from blood pressure to blood sugars and more

👀 WATCH AND LEARN

Healthy Oatmeal Snacks, Tastier Than French Fries (3:26)

These crunchy delicious snacks (which are not fried) can be kept for up to 2–3 months:

Want to watch it, but not right now? Bookmark it for later 🔖

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❓ MYSTERY ITEM

Footloose

Hint: today’s mystery item can help you to be footloose and plantar fasciitis-free

YOU MAY HAVE MISSED…

  • Thriving Beyond Fifty (book)

  • Protein: How Much Do We Need, Really?

💊 MAIN FEATURE

Out With The Old…

Fisetin is a flavonoid (specifically, a flavonol), but it’s a little different than most. While it has the usual antioxidant, anti-inflammatory, and anti-cancer properties you might reasonably expect from flavonoids, it has an extra anti-aging trick up its sleeve that most don’t.

❝Fisetin is a flavonol that shares distinct antioxidant properties with a plethora of other plant polyphenols. Additionally, it exhibits a specific biological activity of considerable interest as regards the protection of functional macromolecules against stress which results in the sustenance of normal cells cytoprotection. Moreover, it shows potential as an anti-inflammatory, chemopreventive, chemotherapeutic and recently also senotherapeutic agent❞

Let’s briefly do some due diligence on its expected properties, and then we’ll take a look at its bonus anti-aging effects.

The flavonol that does-it-ol

Because of the similar mechanisms involved, there are three things that often come together, which are:

  • Antioxidant

  • Anti-inflammatory

  • Anticancer

This list often gets expanded to also include:

  • Anti-aging

…although that is usually the last thing to get tested out of that list.

In today’s case, let’s kick it off with…

❝Fisetin (3,3',4',7-tetrahydroxyflavone) is a dietary flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective effects❞

Understanding its anticancer mechanisms

The way that fisetin fights cancer is basically “all the ways”, and this will be important when we get to its special abilities shortly:

❝Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage, and modulate the expressions of Bcl‐2 family proteins in different cancer cell lines (HT‐29, U266, MDA‐MB‐231, BT549, and PC‐3M‐luc‐6), respectively. Further, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin. Fisetin also inhibited cell division and proliferation and invasion as well as lowered the TET1 expression levels. ❞

There’s also more about it than we even have room to quote, here:

Now For What’s New And Exciting: Senolysis

All that selectivity that fisetin exhibits when it comes to “this cell gets to live, and this one doesn’t” actions?

It makes a difference when it comes to aging, too. Because aging and cancer happen by quite similar mechanisms; they’re both DNA-copying errors that get copied forward, to our detriment.

  • In the case of cancer, it’s a cell line that accidentally became immortal and so we end up with too many of them multiplying in one place (a tumor)

  • In the case of aging, it’s the cellular equivalent of “a photocopy of a photocopy of a photocopy” gradually losing information as it goes

In both cases…

The cell must die if we want to live

Critically, and which quality differentiates it from a lot of other flavonoids, fisetin has the ability to selectively kill senescent cells.

To labor the photocopying metaphor, this means there’s an office worker whose job it is to say “this photocopy is barely legible, I’m going to toss this, and then copy directly from the clearest copy we have instead”, thus keeping the documents (your DNA) in pristine condition.

In fisetin’s case, this was first tested in mouse (in vivo) studies, and in human tissue (in vitro) studies, before moving to human clinical studies:

❝Of the 10 flavonoids tested, fisetin was the most potent senolytic.

The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit.❞

There’s lots more science that’s been done to it since that first groundbreaking study though; here’s a more recent example:

Want some?

We don’t sell it, but here for your convenience is an example product on Amazon 😎

Enjoy!

YOU MAY HAVE MISSED…

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📖 ONE-MINUTE BOOK REVIEW

Brain Power: Improve Your Mind as You Age – by Michael Gelb & Kelly Howell

What’s most important when it comes to brain health? Is it the right diet? Supplements? Brain-training? Attitude? Sleep? Physical exercise? Social connections? Something else?

This book covers a lot of bases, including all of the above and more. The authors are not scientists by training and this is not a book of science, so much as a book of aggregated science-based advice from other sources. The authors did consult with many scientists, and their input is shown throughout.

In the category of criticism, nothing here goes very deeply into the science, and there’s also nothing you wouldn’t find we’ve previously written about in a 10almonds article somewhere. But all the same, it’s good to have a wide variety of brain-healthy advices all in one place.

Bottom line: if you’re looking for a one-stop-shop “look after your brain as you age” guide, then this is a good one.

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Wishing you the most well-informed start to the week,

The 10almonds Team