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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    Dr. Sean Young’s “Stick With It” is the science-based heavy-artillery for building new habits. Get practical neurohacking advice backed by solid research.

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  • Unlimited Memory – by Kevin Horsley

    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.

    Premise: there are easily learnable techniques to rapidly (and greatly) improve one’s memory. We’ve touched on some of these methods before at 10almonds, but being a newsletter rather than a book, we’ve not been able to go as deeply into it as Horsley!

    Your memory is far, far, far more powerful than you might realize, and this book will help unlock that. To illustrate…

    Some of the book is given over to what are for most purposes “party tricks”, such as remembering pi to 10,000 places. Those things are fun, even if not as practical in today’s world of rarely needing to even know the actual digits of a phone number. However, they do also serve as a good example of just how much of “super memory” isn’t a matter of hard work, so much as being better organized about it.

    Most of the book is focused on practical methods to improve the useful aspects of memory—including common mistakes!

    If the book has any flaw it’s that the first chapter or so is spent persuading the reader of things we presumably already believe, given that we bought the book. For example, that remembering things is a learnable skill and that memory is functionally limitless. However, we still advise to not skip those chapters as they do contain some useful reframes as well.

    Bottom line: if you read this book you will be astonished by how much you just learned—because you’ll be able to recall whole sections in detail! And then you can go apply that whatever areas of your life you wanted to when you bought the book.

    Get your copy of Unlimited Memory from Amazon today!

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  • Is Cutting Calories The Key To Healthy Long Life?

    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.

    Caloric Restriction with Optimal Nutrition

    Yesterday, we asked you “What is your opinion of caloric restriction as a health practice?” and got the above-depicted, below-described spread of responses:

    • 48% said “It is a robust, scientifically proven way to live longer and healthier”
    • 23% said “It may help us to live longer, but at the cost of enjoying it fully”
    • 17% said “It’s a dangerous fad that makes people weak, tired, sick, and unhealthy”
    • 12% said “Counting calories is irrelevant to good health; the body compensates”

    So… What does the science say?

    A note on terms, first

    “Caloric restriction” (henceforth: CR), as a term, sees scientific use to mean anything from a 25% reduction to a 50% reduction, compared to metabolic base rate.

    This can also be expressed the other way around, “dropping to 60% of the metabolic base rate” (i.e., a 40% reduction).

    Here we don’t have the space to go into much depth, so our policy will be: if research papers consider it CR, then so will we.

    A quick spoiler, first

    The above statements about CR are all to at least some degree True in one way or another.

    However, there are very important distinctions, so let’s press on…

    CR is a robust, scientifically proven way to live longer and healthier: True or False?

    True! This has been well-studied and well-documented. There’s more science for this than we could possibly list here, but here’s a good starting point:

    ❝Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models.

    Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity.

    In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality❞

    Source: Ageing Research Reviews | Calorie restriction in humans: an update

    See also: Caloric restriction in humans reveals immunometabolic regulators of health span

    We could devote a whole article (or a whole book, really) to this, but the super-short version is that it lowers the metabolic “tax” on the body and allows the body to function better for longer.

    CR may help us to live longer, but at the cost of enjoying it fully: True or False?

    True or False, contingently, depending on what’s important to you. And that depends on psychology as much as physiology, but it’s worth noting that there is often a selection bias in the research papers; people ill-suited to CR drop out of the studies and are not counted in the final data.

    Also, relevant for a lot of our readers, most (human-based) studies recruit people over 18 and under 60. So while it is reasonable to assume the same benefits will be carried over that age, there is not nearly as much data for it.

    Studies into CR and Health-Related Quality of Life (HRQoL) have been promising, and/but have caveats:

    ❝In non-obese adults, CR had some positive effects and no negative effects on HRQoL.❞

    Source: Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Non-obese Adults

    ❝We do not know what degree of CR is needed to achieve improvements in HRQoL, but we do know it requires an extraordinary amount of support.

    Therefore, the incentive to offer this intervention to a low-risk, normal or overweight individual is lacking and likely not sustainable in practice.❞

    Source: Caloric restriction improves health-related quality of life in healthy normal weight and overweight individuals

    CR a dangerous fad that makes people weak, tired, sick, and unhealthy: True or False?

    True if it is undertaken improperly, and/or without sufficient support. Many people will try CR and forget that the idea is to reduce metabolic load while still getting good nutrition, and focus solely on the calorie-counting.

    So for example, if a person “saves” their calories for the day to have a night out in a bar where they drink their calories as alcohol, then this is going to be abysmal for their health.

    That’s an extreme example, but lesser versions are seen a lot. If you save your calories for a pizza instead of a night of alcoholic drinks, then it’s not quite so woeful, but for example the nutrition-to-calorie ratio of pizza is typically not great. Multiply that by doing it as often as not, and yes, someone’s health is going to be in ruins quite soon.

    Counting calories is irrelevant to good health; the body compensates: True or False?

    True if by “good health” you mean weight loss—which is rarely, if ever, what we mean by “good health” here at 10almonds (unless we clarify such), but it’s a very common association and indeed, for some people it’s a health goal. You cannot sustainably and healthily lose weight by CR alone, especially if you’re not getting optimal nutrition.

    Your body will notice that you are starving, and try to save you by storing as much fat as it can, amongst other measures that will similarly backfire (cortisol running high, energy running low, etc).

    For short term weight loss though, yes, it’ll work. At a cost. That we don’t recommend.

    ❝By itself, decreasing calorie intake will have a limited short-term influence.❞

    Source: Reducing Calorie Intake May Not Help You Lose Body Weight

    See also…

    ❝Caloric restriction is a commonly recommended weight-loss method, yet it may result in short-term weight loss and subsequent weight regain, known as “weight cycling”, which has recently been shown to be associated with both poor sleep and worse cardiovascular health❞

    Source: Dieting Behavior Characterized by Caloric Restriction

    In summary…

    Caloric restriction is a well-studied area of health science. We know:

    • Practised well, it can extend not only lifespan, but also healthspan
    • Practised well, it can improve mood, energy, sexual function, and the other things people fear losing
    • Practised badly, it can be ruinous to the health—it is critical to practise caloric restriction with optimal nutrition.
    • Practised badly, it can lead to unhealthy weight loss and weight regain

    One final note…

    If you’ve tried CR and hated it, and you practised it well (e.g., with optimal nutrition), then we recommend just not doing it.

    You could also try intermittent fasting instead, for similar potential benefits. If that doesn’t work out either, then don’t do that either!

    Sometimes, we’re just weird. It can often be because of a genetic or epigenetic quirk. There are usually workarounds, and/but not everything that’s right for most people will be right for all of us.

    Take care!

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  • Yes, adults can develop food allergies. Here are 4 types you need to know about

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    If you didn’t have food allergies as a child, is it possible to develop them as an adult? The short answer is yes. But the reasons why are much more complicated.

    Preschoolers are about four times more likely to have a food allergy than adults and are more likely to grow out of it as they get older.

    It’s hard to get accurate figures on adult food allergy prevalence. The Australian National Allergy Council reports one in 50 adults have food allergies. But a US survey suggested as many as one in ten adults were allergic to at least one food, with some developing allergies in adulthood.

    What is a food allergy

    Food allergies are immune reactions involving immunoglobulin E (IgE) – an antibody that’s central to triggering allergic responses. These are known as “IgE-mediated food allergies”.

    Food allergy symptoms that are not mediated by IgE are usually delayed reactions and called food intolerances or hypersensitivity.

    Food allergy symptoms can include hives, swelling, difficulty swallowing, vomiting, throat or chest tightening, trouble breathing, chest pain, rapid heart rate, dizziness, low blood pressure or anaphylaxis.

    Hives
    Symptoms include hives. wisely/Shutterstock

    IgE-mediated food allergies can be life threatening, so all adults need an action management plan developed in consultation with their medical team.

    Here are four IgE-mediated food allergies that can occur in adults – from relatively common ones to rare allergies you’ve probably never heard of.

    1. Single food allergies

    The most common IgE-mediated food allergies in adults in a US survey were to:

    • shellfish (2.9%)
    • cow’s milk (1.9%)
    • peanut (1.8%)
    • tree nuts (1.2%)
    • fin fish (0.9%) like barramundi, snapper, salmon, cod and perch.

    In these adults, about 45% reported reacting to multiple foods.

    This compares to most common childhood food allergies: cow’s milk, egg, peanut and soy.

    Overall, adult food allergy prevalence appears to be increasing. Compared to older surveys published in 2003 and 2004, peanut allergy prevalence has increased about three-fold (from 0.6%), while tree nuts and fin fish roughly doubled (from 0.5% each), with shellfish similar (2.5%).

    While new adult-onset food allergies are increasing, childhood-onset food allergies are also more likely to be retained into adulthood. Possible reasons for both include low vitamin D status, lack of immune system challenges due to being overly “clean”, heightened sensitisation due to allergen avoidance, and more frequent antibiotic use.

    Woman holds coffee and pastry
    Some adults develop allergies to cow’s milk, while others retain their allergy from childhood. Sarah Swinton/Unsplash

    2. Tick-meat allergy

    Tick-meat allergy, also called α-Gal syndrome or mammalian meat allergy, is an allergic reaction to galactose-alpha-1,3-galactose, or α-Gal for short.

    Australian immunologists first reported links between α-Gal syndrome and tick bites in 2009, with cases also reported in the United States, Japan, Europe and South Africa. The US Centers for Disease Control estimates about 450,000 Americans could be affected.

    The α-Gal contains a carbohydrate molecule that is bound to a protein molecule in mammals.

    The IgE-mediated allergy is triggered after repeated bites from ticks or chigger mites that have bitten those mammals. When tick saliva crosses into your body through the bite, antibodies to α-Gal are produced.

    When you subsequently eat foods that contain α-Gal, the allergy is triggered. These triggering foods include meat (lamb, beef, pork, rabbit, kangaroo), dairy products (yoghurt, cheese, ice-cream, cream), animal-origin gelatin added to gummy foods (jelly, lollies, marshmallow), prescription medications and over-the counter supplements containing gelatin (some antibiotics, vitamins and other supplements).

    Tick-meat allergy reactions can be hard to recognise because they’re usually delayed, and they can be severe and include anaphylaxis. Allergy organisations produce management guidelines, so always discuss management with your doctor.

    3. Fruit-pollen allergy

    Fruit-pollen allergy, called pollen food allergy syndrome, is an IgE-mediated allergic reaction.

    In susceptible adults, pollen in the air provokes the production of IgE antibodies to antigens in the pollen, but these antigens are similar to ones found in some fruits, vegetables and herbs. The problem is that eating those plants triggers an allergic reaction.

    The most allergenic tree pollens are from birch, cypress, Japanese cedar, latex, grass, and ragweed. Their pollen can cross-react with fruit and vegetables, including kiwi, banana, mango, avocado, grapes, celery, carrot and potato, and some herbs such as caraway, coriander, fennel, pepper and paprika.

    Fruit-pollen allergy is not common. Prevalence estimates are between 0.03% and 8% depending on the country, but it can be life-threatening. Reactions range from itching or tingling of lips, mouth, tongue and throat, called oral allergy syndrome, to mild hives, to anaphylaxis.

    4. Food-dependent, exercise-induced food allergy

    During heavy exercise, the stomach produces less acid than usual and gut permeability increases, meaning that small molecules in your gut are more likely to escape across the membrane into your blood. These include food molecules that trigger an IgE reaction.

    If the person already has IgE antibodies to the foods eaten before exercise, then the risk of triggering food allergy reactions is increased. This allergy is called food-dependent exercise-induced allergy, with symptoms ranging from hives and swelling, to difficulty breathing and anaphylaxis.

    Man stands on court
    This type of allergy is extremely rare. Ben O’Sullivan/Unsplash

    Common trigger foods include wheat, seafood, meat, poultry, egg, milk, nuts, grapes, celery and other foods, which could have been eaten many hours before exercising.

    To complicate things even further, allergic reactions can occur at lower levels of trigger-food exposure, and be more severe if the person is simultaneously taking non-steroidal inflammatory medications like aspirin, drinking alcohol or is sleep-deprived.

    Food-dependent exercise-induced allergy is extremely rare. Surveys have estimated prevalence as between one to 17 cases per 1,000 people worldwide with the highest prevalence between the teenage years to age 35. Those affected often have other allergic conditions such as hay fever, asthma, allergic conjunctivitis and dermatitis.

    Allergies are a growing burden

    The burden on physical health, psychological health and health costs due to food allergy is increasing. In the US, this financial burden was estimated as $24 billion per year.

    Adult food allergy needs to be taken seriously and those with severe symptoms should wear a medical information bracelet or chain and carry an adrenaline auto-injector pen. Concerningly, surveys suggest only about one in four adults with food allergy have an adrenaline pen.

    If you have an IgE-mediated food allergy, discuss your management plan with your doctor. You can also find more information at Allergy and Anaphylaxis Australia.

    Clare Collins, Laureate Professor in Nutrition and Dietetics, University of Newcastle

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Non-Alcohol Mouthwash vs Alcohol Mouthwash – 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 non-alcohol mouthwash to alcohol mouthwash, we picked the alcohol.

    Why?

    Note: this is a contingent choice and is applicable to most, but not all, people.

    In short, there has been some concern about alcohol mouthwashes increasing cancer risk, but research has shown this is only the case if you already have an increased risk of oral cancer (for example if you smoke, and/or have had an oral cancer before).

    For those for whom this is not the case (for example, if you don’t smoke, and/or have no such cancer history), then best science currently shows that alcohol mouthwash does not cause any increased risk.

    What about non-alcohol mouthwashes? Well, they have a different problem; they usually use chlorine-based chemicals like chlorhexidine or cetylpyridinium chloride, which are (exactly as the label promises) exceptionally good at killing oral bacteria.

    (They’d kill us too, at higher doses, hence: swill and spit)

    Unfortunately, much like the rest of our body, our mouth is supposed to have bacteria there and bad things happen when it doesn’t. In the case of our oral microbiome, cleaning it with such powerful antibacterial agents can kill our “good” bacteria along with the bad, which lowers the pH of our saliva (that’s bad; it means it is more acidic), and thus indirectly erodes tooth enamel.

    You can read more about the science of all of the above (with references), here:

    Toothpastes & Mouthwashes: Which Help And Which Harm?

    Summary:

    For most people, alcohol mouthwashes are a good way to avoid the damage that can be done by chlorhexidine in non-alcohol mouthwashes.

    Here are some examples, but there will be plenty in your local supermarket:

    Non-Alcohol, by Colgate | Alcohol, by Listerine

    If you have had oral cancer, or if you smoke, then you may want to seek a third alternative (and also, please, stop smoking if you can).

    Or, really, most people could probably skip mouthwashes, if you’ve good oral care already by other means. See also:

    Toothpastes & Mouthwashes: Which Help And Which Harm?

    (yes, it’s the same link as before, but we’re now drawing your attention to the fact it has information about toothpastes too)

    If you do want other options though, might want to check out:

    Less Common Oral Hygiene Options ← miswak sticks are especially effective

    Take care!

    Don’t Forget…

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    Learn to Age Gracefully

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  • Tempeh vs Tofu – 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 tempeh to tofu, we picked the tempeh.

    Why?

    Per 100g, tempeh has about 1.5x as many calories, about 2x as much protein, about 3x as much fiber, and about 4x the carbohydrates.

    Which latter sounds like a lot, but really, the amounts here are small—tempeh is under 12% carbohydrates, and most of that is treated by the body as fiber (e.g. it’s a resistant starch).

    Both have no sugar, and both have more or less the same (tiny) amount of fat.

    Micronutrients, you ask? As they’re both made from soybeans, the micronutrient profiles are similar, but exact amounts will depend on the method used, so by all means check labels if comparing products in store. By and large, there’s usually not much difference, though.

    You can see sample stats here:

    Tempeh | Tofu

    In summary

    Both are great, and/but tempeh is the more nutrient-dense of the two.

    Therefore, tempeh is the healthier option, unless you are on a very strictly calorie-controlled diet, in which case, tofu will give you more quantity per calorie.

    Enjoy!

    Don’t Forget…

    Did you arrive here from our newsletter? Don’t forget to return to the email to continue learning!

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  • Staying Sane In A Hyper-Connected World

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    Staying Sane In A Hyper-Connected World

    There’s a war over there, a genocide in progress somewhere else, and another disease is ravaging the population of somewhere most Americans would struggle to point out on the map. Not only that, but that one politician is at it again, and sweeping wildfires are not doing climate change any favors.

    To borrow an expression from Gen-Z…

    “Oof”.

    A Very Modern Mental Health Menace

    For thousands of years, we have had wars and genocides and plagues and corrupt politicians and assorted major disasters. Dire circumstances are not new to us as a species. So what is new?

    As some reactionary said during the dot-com boom, “the Internet doesn’t make people stupid; it just makes their stupidity more accessible”.

    The same is true now of The Horrors™.

    The Internet doesn’t, by and large, make the world worse. But what it does do is make the bad things much, much more accessible.

    Understanding and empathy are not bad things, but watch out…

    • When soldiers came home from the First World War, those who hadn’t been there had no conception of the horrors that had been endured. That made it harder for the survivors to get support. That was bad.
    • Nowadays, while mass media covering horrors certainly doesn’t convey the half of it, even the half it does convey can be overwhelming. This is also bad.

    The insidious part is: while people are subjectively reporting good physical/mental health, the reports of the symptoms of poor physical/mental health from the same population do not agree:

    Stress in America 2023: A nation grappling with psychological impacts of collective trauma

    Should we just not watch the news?

    In principle that’s an option, but it’s difficult to avoid, unless you truly live under a rock, and also do not frequent any social media at all. And besides, isn’t it our duty as citizens of this world to stay informed? How else can we make informed choices?

    Staying informed, mindfully

    There are steps that can be taken to keep ourselves informed, while protecting our mental health:

    • Choose your sources wisely. Primary sources (e.g. tweets and videos from people who are there) will usually be most authentic, but also most traumatizing. Dispassionate broadsheets may gloss over or misrepresent things more (something that can be countered a bit by reading an opposing view from a publication you hate on principle), but will offer more of an emotional buffer.
    • Boundary your consumption of the news. Set a timer and avoid doomscrolling. Your phone (or other device) may help with this if you set a screentime limit per app where you consume that kind of media.
    • Take (again, boundaried) time to reflect. If you don’t, your brain will keep grinding at it “like a fork in the garbage disposal”. Talking about your feelings on the topic with a trusted person is great; journaling is also a top-tier more private option.
    • If you feel helpless, help. Taking even small actions to help in the face of suffering somewhere else (e.g. donating to relief funds, engaging in advocacy / hounding your government about it), can help alleviate feelings of anguish and helplessness. And of course, as a bonus, it actually helps in the real world too.
    • When you relax, relax fully. Even critical care doctors need downtime, nobody can be “always on” without burning out. So whatever distracts and relaxes you completely, make sure to make time for that too.

    Want to know more?

    That’s all we have room for today, but you might like to check out:

    You also might like our previous main features:

    Take care!

    Don’t Forget…

    Did you arrive here from our newsletter? Don’t forget to return to the email to continue learning!

    Learn to Age Gracefully

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