Fisetin: The Anti-Aging Assassin

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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❞

~ Dr. Grynkiewicz & Dr. Demchuk

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❞

~ Dr. Harish Pal et al.

Read more: Fisetin and Its Role in Chronic Diseases

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. ❞

~ Dr. Muhammad Imran et al.

Read more: Fisetin: An anticancer perspective

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

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

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.❞

~ Dr. Matthew Yousefzadeh et al.

Read in full: Fisetin is a senotherapeutic that extends health and lifespan

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

Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection

Want some?

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

Enjoy!

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    Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!

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    So, no question/request too big or small

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    “I would like to read more on loneliness, meetup group’s for seniors. Thank you”

    Well, 10almonds is an international newsletter, so it’s hard for us to advise about (necessarily: local) meetup groups!

    But a very popular resource for connecting to your local community is Nextdoor, which operates throughout the US, Canada, Australia, and large parts of Europe including the UK.

    In their own words:

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  • Are Electrolyte Supplements Worth It?

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    When To Take Electrolytes (And When We Shouldn’t!)

    Any sports nutrition outlet will sell electrolyte supplements. Sometimes in the form of sports drinks that claim to be more hydrating than water, or tablets that can be dissolved in water to make the same. How do they work, and should we be drinking them?

    What are electrolytes?

    They’re called “electrolytes” because they are ionized particles (so, they have a positive or negative electrical charge, depending on which kind of ion they are) that are usually combined in the form of salts.

    The “first halves” of the salts include:

    • Sodium
    • Potassium
    • Calcium
    • Magnesium

    The “second halves” of the salts include:

    • Chloride
    • Phosphate
    • Bicarbonate
    • Nitrate

    It doesn’t matter too much which way they’re combined, provided we get what we need. Specifically, the body needs them in a careful balance. Too much or too little, and bad things will start happening to us.

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    Why might we need to supplement?

    Firstly, of course, you might have a dietary deficiency. Magnesium deficiency in particular is very common in North America, as people simply do not eat as much greenery as they ideally would.

    But, also, you might sweat out your electrolytes, in which case, you will need to replace them.

    In particular, endurance training and High Intensity Interval Training are likely to prompt this.

    However… Are you in a rush? Because if not, you might just want to recover more slowly:

    ❝Vigorous exercise and warm/hot temperatures induce sweat production, which loses both water and electrolytes. Both water and sodium need to be replaced to re-establish “normal” total body water (euhydration).

    This replacement can be by normal eating and drinking practices if there is no urgency for recovery.

    But if rapid recovery (<24 h) is desired or severe hypohydration (>5% body mass) is encountered, aggressive drinking of fluids and consuming electrolytes should be encouraged to facilitate recovery❞

    Source: Fluid and electrolyte needs for training, competition, and recovery

    Should we just supplement anyway, as a “catch-all” to be sure?

    Probably not. In particular, it is easy to get too much sodium in one’s diet, let alone by supplementation.And, oversupplementation of calcium is very common, and causes its own health problems. See:

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    Well, that’s not helpful. Any clearer pointers?

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    • It is recommended that individuals begin exercise when adequately hydrated.
      • This can be facilitated by drinking 400 mL to 600 mL of fluid 2 hours before beginning exercise and drinking sufficient fluid during exercise to prevent dehydration from exceeding 2% body weight.
    • A practical recommendation is to drink small amounts of fluid (150-300 mL) every 15 to 20 minutes of exercise, varying the volume depending on sweating rate.
      • During exercise lasting less than 90 minutes, water alone is sufficient for fluid replacement
      • During prolonged exercise lasting longer than 90 minutes, commercially available carbohydrate electrolyte beverages should be considered to provide an exogenous carbohydrate source to sustain carbohydrate oxidation and endurance performance.
    • Electrolyte supplementation is generally not necessary because dietary intake is adequate to offset electrolytes lost in sweat and urine; however, during initial days of hot-weather training or when meals are not calorically adequate, supplemental salt intake may be indicated to sustain sodium balance.

    Source: Water and electrolyte requirements for exercise

    Bonus tip:

    We’ve talked before about the specific age-related benefits of creatine supplementation, but if you’re doing endurance training or HIIT, you might also want to consider a creatine-electrolyte combination sports drink (even if you make it yourself):

    Creatine-electrolyte supplementation improves repeated sprint cycling performance: a double-blind randomized control study

    Where can I get electrolyte supplements?

    They’re easy to find in any sports nutrition store, or you can buy them online; here’s an example product on Amazon for your convenience

    You can also opt for natural and/or homemade electrolyte drinks:

    Healthline | 8 Healthy Drinks Rich in Electrolytes

    Enjoy!

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    This is a supremely low-effort, high-yield dish. It’s a nutritional tour-de-force, and very pleasing to the tastebuds too. We use flageolet beans in this recipe; they are small immature kidney beans. If they’re not available, using kidney beans or really any other legume is fine.

    You will need

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    Method

    (we suggest you read everything at least once before doing anything)

    1) Preheat the oven to 350℉ / 180℃.

    2) Mix all the ingredients (except the tomatoes and herbs) in a big mixing bowl, ensuring even distribution.

    2) Add the tomatoes. The reason we didn’t add these before is because it would interfere with the oil being distributed evenly across the vegetables.

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    4) Stir, add the chopped herbs, stir again, and return to the oven for another 30 minutes.

    5) Serve (hot or cold), adding any herb garnish you wish to use.

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    Take care!

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    Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!

    In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!

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    ❝I’d like to read articles on gut health and anxiety❞

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