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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  • Hello Sleep – by Dr. Jade Wu

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    We’ve reviewed other sleep books before, so what makes this one stand out?

    Mostly, it’s because this one takes quite a different approach.

    While still giving a nod to the sensible advice you’ve already read in many places (including here at 10almonds), Dr. Wu looks to help the reader avoid falling into the trap (or: help the reader get out of the trap, if already there) of focussing so much on getting better sleep that it becomes an all-consuming stressor that takes up much of the day thinking about it, and guess what, much of the night too, because you’re busy working out how sleep-deprived you’re going to be tomorrow.

    Instead, Dr. Wu recommends to work with your body rather than against it, worry less, and ultimately sleep better. Of course, the “how” of this is what makes most of the book.

    She does also give chapters on things that may be different for you, based on such things as hormones, age, or medical conditions.

    The writing style is pop-science but with frequent references to scientific papers as appropriate, making good science very accessible.

    Bottom line: if you’ve tried everything else and/but good sleep still eludes you, this book will help you to end the battle and make friends with your sleep (a metaphor the author uses throughout the book, by the way).

    Click here to check out Hello Sleep, and indeed get better sleep!

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  • Savory Protein Crêpe

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Pancakes have a bad reputation healthwise, but they don’t have to be so. Here’s a very healthy crêpe recipe, with around 20g of protein per serving (which is about how much protein most people’s body’s can use at one sitting) and a healthy dose of fiber too:

    You will need

    Per crêpe:

    • ½ cup milk (your preference what kind; we recommend oat milk for this)
    • 2 oz chickpea flour (also called garbanzo bean flour, or gram flour)
    • 1 tsp nutritional yeast
    • 1 tsp ras el-hanout (optional but tasty and contains an array of beneficial phytochemicals)
    • 1 tsp dried mixed herbs
    • ⅛ tsp MSG or ¼ tsp low-sodium salt

    For the filling (also per crêpe):

    • 6 cherry tomatoes, halved
    • Small handful baby spinach
    • Extra virgin olive oil

    Method

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

    1) Mix the dry crêpe ingredients in a bowl, and then stir in the milk, whisking to mix thoroughly. Leave to stand for at least 5 minutes.

    2) Meanwhile, heat a little olive oil in a skillet, add the tomatoes and fry for 1 minute, before adding the spinach, stirring, and turning off the heat. As soon as the spinach begins to wilt, set it aside.

    3) Heat a little olive oil either in the same skillet (having been carefully wiped clean) or a crêpe pan if you have one, and pour in a little of the batter you made, tipping the pan so that it coats the pan evenly and thinly. Once the top is set, jiggle the pan to see that it’s not stuck, and then flip your crêpe to finish on the other side.

    If you’re not confident of your pancake-tossing skills, or your pan isn’t good enough quality to permit this, you can slide it out onto a heatproof chopping board, and use that to carefully turn it back into the pan to finish the other side.

    4) Add the filling to one half of the crêpe, and fold it over, pushing down at the edges with a spatula to make a seal, cooking for another 30 seconds or so. Alternatively, you can just serve a stack of crêpes and add the filling at the table, folding or rolling per personal preference:

    Enjoy!

    Want to learn more?

    For those interested in some of the science of what we have going on today:

    Take care!

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  • We Are Such Stuff As Fish Are Made Of

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Research Review: Collagen

    For something that’s a very popular supplement, not many people understand what collagen is, where it comes from, or what it does.

    In a nutshell:

    Collagen is a kind of protein. Our bodies make it naturally, and we can also get more in our diet and/or take extra as a supplement.

    Our bodies use collagen in connective tissue, skin, tendon, bone, and cartilage. It has many functions, but a broad description would be “holding things together”.

    As we get older, our bodies produce less collagen. Signs of this include wrinkles, loss of skin hydration, and joint pain.

    Quick test: pinch the skin on the middle of the back of one of your hands, and then watch what happens when you get low. How quickly and easily did your skin returns to its original shape?

    If it was pretty much instantanous and flawless, congratulations, you have plenty of collagen (and also elastin). If you didn’t, you are probably low on both!

    (they are quite similar proteins and are made from the same base “stuff”, so if you’re low on one, you’ll usually be low on both)

    Quick note: A lot of research out there has been funded by beauty companies, so we had our work cut out for us today, and have highlighted where any research may be biased.

    More than skin deep

    While marketing for collagen is almost exclusively aimed at “reduce wrinkles and other signs of aging”, it does a lot more than that.

    You remember we mentioned that many things from the bones outward are held together by collagen? We weren’t kidding…

    Read: Osteoporosis, like skin ageing, is caused by collagen loss which is reversible

    Taking extra collagen isn’t the only way

    We can’t (yet!) completely halt the age-related loss of collagen, but we can slow it, with our lifestyle choices:

    Can I get collagen from food?

    Yep! Just as collagen holds our bodies together, it holds the bodies of other animals together. And, just like collagen is found in most parts of our body but most plentifully in our skin and bones, that’s what to eat to get collagen from other animals, e.g:

    • Chicken skin
    • Fish skin
    • Bone broth ← health benefits and recipes at this link!

    What about vegans?

    Yes, vegans are also held together by collagen! We do not, however, recommend eating their skin or boiling their bones into broth. Ethical considerations aside, cannibalism can give you CJD!

    More seriously, if you’re vegan, you can’t get collagen from a plant-based diet, but you can get the stuff your body uses to make collagen. Basically, you want to make sure you get plenty of:

    Read: Diet and Dermatology: The Role of a Whole-food, Plant-based Diet in Preventing and Reversing Skin Aging

    Just be sure to continue to remember to avoid highly-processed foods. So:

    • Soy mince/chunks whose ingredients list reads: “soya”? Yes!
    • The Incredible Burger or Linda McCartney’s Sausages? Sadly less healthy

    Read: Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet

    Meat-eaters might want to read that one too. By far the worst offenders for AGEs (Advanced Glycation End Products, which can not only cause collagen to stiffen, but also inactivate proteins responsible for collagen repair, along with doing much more serious damage to your body’s natural functions) include:

    • Hot dogs
    • Bacon
    • Fried/roasted/grilled meats

    Is it worth it as a supplement?

    That depends on you, your age, and your lifestyle, but it’s generally considered safe*

    *if you have a seafood allergy, be careful though, as many supplements are from fish or shellfish—you will need to find one that’s free from your allergen

    Also, all collagen is animal-derived. So if you’re a vegan, decide for yourself whether this constitutes medicine and if so, whether that makes it ethically permissible to you.

    With that out of the way:

    What the science says on collagen supplementation

    Collagen for skin

    Read: Effects of collagen supplementation on skin aging (systematic review and meta-analysis)

    The short version is that they selected 19 studies with over a thousand participants in total, and they found:

    In the meta-analysis, a grouped analysis of studies showed favorable results of hydrolyzed collagen supplementation compared with placebo in terms of skin hydration, elasticity, and wrinkles.

    The findings of improved hydration and elasticity were also confirmed in the subgroup meta-analysis.

    Based on results, ingestion of hydrolyzed collagen for 90 days is effective in reducing skin aging, as it reduces wrinkles and improves skin elasticity and hydration.

    Caveat: while that systematic review had no conflicts of interests, at least some of the 19 studies will have been funded by beauty companies. Here are two, so that you know what that looks like:

    Funded by Quiris to investigate their own supplement, Elasten®:

    A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density

    Funded by BioCell to investigate their own supplement, BioCell Collagen:

    The Effects of Skin Aging Associated with the Use of BioCell Collagen

    A note on funding bias: to be clear, the issue is not that the researchers might be corrupt (though that could happen).

    The issue is more that sometimes companies will hire ten labs to do ten research studies… and then pull funding from ones whose results aren’t going the way they’d like.

    So the “best” (for them) study is the one that gets published.

    Here’s another systematic review—like the one at the top of this section—that found the same, with doses ranging from 2.5g–15g per day for 8 weeks or longer:

    Read: Oral Collagen Supplementation: A Systematic Review of Dermatological Applications

    Again, some of those studies will have been funded by beauty companies. The general weight of evidence does seem clear and favorable, though.

    Collagen for bones

    Here, we encountered a lot less in the way of potential bias, because this is simply marketed a lot less. Despite being arguably far more important!

    We found a high quality multi-vector randomized controlled study with a sample size of 131 postmenopausal women. They had these women take 5g collagen supplement (or placebo), and studied the results over the course of a year.

    They found:

    • The intake of the supplement increased bone mineral density (BMD)
    • Supplementation was also associated with a favorable shift in bone markers, indicating:
      • increased bone formation
      • reduced bone degradation

    Read: Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Wome

    A follow-up study with 31 of these women found that taking 5 grams of collagen daily for a total of 4 years was associated with a progressive increase in BMD.

    You might be wondering if collagen also helps against osteoarthritis.

    The answer is: yes, it does (at least, it significantly reduces the symptoms)

    Read: Effect of collagen supplementation on osteoarthritis symptoms

    In summary:

    • You need collagen for health skin, bones, joints, and more
    • Your body makes collagen from your food
    • You can help it by getting plenty of protein, vitamins, and minerals
    • You can also help it by not doing the usual Bad Things™ (smoking, drinking, eating processed foods, especially processed meats)
    • You can also eat collagen directly in the form of other animals’ skin and bones
    • You can also buy collagen supplements (but watch out for allergens)

    Want to try collagen supplementation?

    We don’t sell it (or anything else), but for your convenience…

    Check it out: Hydrolyzed Collagen Peptides (the same as in most of the above studies), 90 days supply at 5g/day

    We selected this one because it’s the same kind used in many of the studies, and it doesn’t contain any known allergens.

    It’s bovine collagen, meaning it’s from cows, so it’s not vegan, and also some subscribers may want to abstain for religious reasons. We respect that, and/but make our recommendations based solely on the science of health and productivity.

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  • Low-Dose Aspirin & Anemia

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    We recently wrote about…

    How To Survive A Heart Attack When You’re Alone

    …and one of the items was “if you have aspirin readily available, then after calling an ambulance is the time to take it—but don’t exert yourself trying to find some”.

    But what of aspirin as a preventative?

    Many people take low-dose aspirin daily as a way to reduce the risk of atherothrombosis specifically (and thus, indirectly, they hope to reduce the risk of heart attacks).

    The science of how helpful this is both clear and complicated—that is to say, the stats are not ambiguous*, but there are complicating factors of which many people are unaware.

    *it will reduce the overall risk of cardiovascular events, but will not affect CVD mortality; in other words, it may improve your recovery from minor cardiac events, but is not likely to save you from major ones.

    And also, it has unwanted side effects that can constitute a more relevant threat for many people. We’ll share more on that at the end of today’s article, but first…

    A newly identified threat from daily aspirin use

    A large (n=313,508) study of older adults (median age 73) were sorted into those who used low-dose aspirin as a preventative, and those who did not.

    The primary outcome was incidence of anemia sufficient to require treatment, and the secondary outcome was major bleeding. And, at least 1 in 5 of those who experienced anemia also experienced bleeding.

    The bleeding issue was not “newly identified” and will not surprise many people; after all, the very reason that aspirin is taken as a CVD preventative is for its anti-clotting property of allowing blood to flow more freely.

    The anemia, however, has been getting increasing scientific scrutiny lately, after long going unnoticed in the wild. Given that anemia also gives the symptom “dizziness”, this is also a significant threat for increasing the incidence of falls in the older population, too, which can of course lead to serious complications and ultimately death.

    Here’s the paper itself:

    Low-Dose Aspirin and Risk of Anaemia in Older Adults: Insights from a Danish Register-based Cohort Study

    Want to know more?

    As promised, here’s what we wrote previously about some of aspirin’s other risks:

    Aspirin, CVD Risk, & Potential Counter-Risks

    Take care!

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    Learn to Age Gracefully

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  • Brain Maker – by Dr. David Perlmutter

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Regular 10almonds readers probably know about the gut-brain connection already, so what’s new here?

    Dr. David Perlmutter takes us on a tour of gut and brain health, specifically, the neuroprotective effect of healthy gut microbiota.

    This seems unlikely! After all, vagus nerve or no, the gut microbiota are confined to the gut, and the brain is kept behind the blood-brain barrier. So how does one thing protect the other?

    Dr. Perlmutter presents the relevant science, and the honest answer is, we’re not 100% sure how this happens! We do know part of it: that bad gut microbiota can result in a “leaky gut”, and that may in turn lead to such a thing as a “leaky brain”, where the blood-brain barrier has been compromised and some bad things can get in with the blood.

    When it comes to gut-brain health…

    Not only is the correlation very strong, but also, in tests where someone’s gut microbiota underwent a radical change, e.g. due to…

    • antibiotics (bad)
    • fasting (good)
    • or a change in diet (either way)

    …their brain health changed accordingly—something we can’t easily check outside of a lab, but was pretty clear in those tests.

    We’re also treated to an exposé on the links between gut health, brain health, inflammation, and dementia… Which links are extensive.

    In closing, we’ll mention that throughout this book we’re also given many tips and advices to improve our gut/brain health, reverse damage done already, and set ourselves up well for the future.

    Click here to check out “Brain Maker” on Amazon and take care of this important part of your health!

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  • White Potato vs Sweet Potato – Which is Healthier?

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Our Verdict

    When comparing white potatoes to sweet potatoes, we picked the sweet potatoes.

    Why?

    In terms of macros, sweet potatoes are a little lighter on carbs and calories, though in the case of sugar and fiber, sweet potato has a few grams more of each, per potato. However, when an average sweet potato’s 7g of sugar are held against its 4g of fiber, this (much like with fruit!) not a sugar you need to avoid.

    See also: Which Sugars Are Healthier, And Which Are Just The Same?

    The glycemic index of a sweet potato is also lower than that of a white potato, so the sugars it does have are slower-release.

    Sweet potatoes famously are good sources of vitamin A and beta-carotene, which important nutrients white potatoes cannot boast.

    Both plants are equally good sources of potassium and vitamin C.

    Summary

    Both are good sources of many nutrients, and any nutritional health-hazards associated with them come with the preparation (for example, frying introduces unhealthy fats, and mashing makes the glycemic index skyrocket, and cooking with salt increases the salt content).

    Baking either is great (consider stuffing them with delicious well-seasoned beans and/or tomatoes; if you make it yourself, pesto can be a great option too, as can cheese if you’re so-inclined and judicious with choice and quantity) and preserves almost all of their nutrients. Remember that nearly 100% of the fiber is in the skin, so you do want to eat that.

    The deciding factor is: sweet potatoes are good sources of a couple more valuable nutrients that white potatoes aren’t, and come out as the overall healthiest for that reason.

    Enjoy!

    Don’t Forget…

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