In this Ramble: What peace from mind requires, the science of aging, a CBD oil primer, the poor damn bees, and a trial run with personalized nutrition

1. The Long Debate on Money and Happiness

2. On The Cusp of A More Vibrant Way to Age?

3. About All That CBD Oil Advertised Everywhere

4. Of Mites, Men and Murder Hornets

5. Follow Along As We Kick The Tires on Zoe, The PREDICT 2 Nutrition Study App

6. Zen

Picture Credit: “Crystal Hues” by Erin Hanson, www.erinhanson.com

A Piece of Mind on Peace from Mind

Does money buy happiness?

Yes or no question, right?

Is it a straight yes or no question though?

Is a possible answer that some amount of money is necessary but not sufficient, in itself, for happiness?

You may be shocked to learn “the necessary, but not sufficient argument” gets made.

Take Aristotle in his Nicomachean Ethics. Aristotle was trying to make an argument for a practical guide to happiness. He defined the happy person as one who acted virtuously, with those actions in harmony with internal virtue, in endeavors that made them happy and had a certain amount of exterior goods. To Aristotle, though, you could not tell if a person was happy until their entire life had been lived—disaster might strike, fortune might rob them of their, well, fortune, and they might die unhappy if not miserable. But a wealthy miser might act unjustly, or intemperately, and thus not meet Aristotle’s definition of happy. Aristotle also acknowledged that adversity of fortune provides an opportunity for virtues such as prudence, fortitude and courage to battle back. However, he could not conceive of a common definition of happiness that would find a person homeless, destitute, and hungry and call their life “happy,” so appended “exterior goods” to his definition of a happy life.

So you can certainly suggest that Aristotle believed wealth necessary, but not sufficient for happiness. He may have been the first, but he is not the last.

For a more modern take, Naval released his thoughts on practical wisdom (Naval’s emphasis) earlier this year. Frankly, there is a lot to think about in his practical wisdom, so this will be a short take. We must also make clear that Naval, like Aristotle, wasn’t searching for absolute wisdom, but the path that would allow most people some measure of wisdom. Practical.

Naval made an Aristotlian argument—peace of mind (what Naval defines as “happiness”) requires that your material needs be met. “At least for the modern society,” he caveated. This is necessary because to NOT have material needs met is a danger to health and safety. Further, Naval argued that money in the modern world gave you freedom and time—two prerequisites to his definition of peace of mind. Naval defines “peace of mind” as “peace from mind.” Truly in the moment, with no preoccupation with things you “need” to do, and so free to take the time to let the mind and its worries fall away. If your material needs are not met, Naval argues, you will not have peace from mind, as the mind will worry about not having money, and the safety, health, freedom and time that money provides.

He recognized this was a surprising claim. Most of philosophers and sages of antiquity instead described wealth as a burden, and source of anxiety. Naval counters by stating that health is the first true necessity (quoting Confucius that a sick man wants only one thing, a well man wants 10,000 things). He also argues that removing the desire for material things by having them is easier (and thus more practical) than simply releasing the desire for things you do not have. “Monks speak only of sex, and prostitutes only of God,” he quotes. Saints and Buddhas are rare, and “we are consumed by that which we deny ourselves.” To get over our desires, truly, takes decades (if it ever happens), and is “playing [life] on Hard Mode,” as Naval puts it.

Fair points.

Yet it can be done. Diogenes founded the cynic school of philosophy centuries ago, arguing that humanity was not designed by nature for much of what we do. He slept outdoors, lived a hunter-gatherer lifestyle, and so successfully challenged his fellow Greeks for their vanities, hypocrisies and weaknesses that they gave him a state funeral when he died. There is little in the record to suggest he did not have peace from mind, and famously, Diogenes settled a raging political debate merely by walking into the assembly, taking the stage, and throwing one long, withering look around the entire room, which fell silent under his gaze.

Saints and buddhas may be rare—but they do exist.

I think Naval would say that he is focused on practical wisdom though. For the many of us, peace from true renunciation of what is really superfluous is long and hard, and most do not succeed at it in their lifetimes. After Diogenes, the Cynics were never really the same. Few had his dedication to the lifestyle. More practical to meet your material needs, I think Naval (and Aristotle) would say.

Necessary, but not sufficient.

However, I think there is good reason to disagree about the necessity of material wealth for peace of mind, even in the modern world. Even Naval acknowledges that we live in a society of incredible abundance. The average inhabitant of a modern, first world society is wealthier than the richest traders, and wealthiest monarchs, of Aristotle’s day. The challenge in ancient Greece was to meet the first rung of Maslow’s Hierarchy of Needs—basic food and shelter. All across the world, the rates of food insecurity and poverty have been dropping.

Yet, even among all of this material abundance, meeting even what Aristotle was likely referring to as “external goods”, even Naval acknowledges that we may be unhappier than ever.

Is it impossible for a hunter gatherer to have been more content, and happier, than someone living in material abundance in the modern world? Quite possibly. Or is there simply a sliding scale, and the “necessary” material abundance is a function of the average of your society?

Otherwise, how would Aristotle and Naval reconcile the rising rates of anxiety, depression (both requiring medication) and addiction (self-medication of anxiety and depression) in modern society? More people than ever should have checked the “necessary” box to put themselves in position for peace of mind/happiness.

Is it that there is too much emphasis on that “necessary” material wealth portion, and not on the insufficiency? Is modern society just not doing the next essential steps for peace of mind/happiness?

Wealth, even great wealth, does not necessarily lead to peace of mind. In some cases, this “necessity” to peace of mind actively detracts from peace of mind! You need only glance at the headlines to know how many unbelievably wealthy people, despite having all their material needs met if not exceeded, are still deeply unhappy and far from what we would call “peaceful.” Such has it always been. Seneca the Younger wrote once of a letter that Emperor Augustus sent to the Roman Senate, to assuage fears and convince them that he could take a vacation from ruling and the empire would not collapse. Augustus never got that freedom, and had to content himself with the mental vacation of describing his plans in his letter. There are plenty of CEOs and politicians who would agree. Money does not necessarily lead to freedom and time, even in the modern era. The homeless person on the street has more truly free time, and far fewer restrictions on what they can say, than many with lofty titles. After all, few really care what a vagrant says—but many are those who, because of their wealth and title, must always be “on”, lest they lose their position. Their material wealth is not security, time and freedom—it is their prison, because its acquisition often required them to play the game, and its retention requires them to keep playing the game. Whether they want to or not.

Augustus Caesar, first emperor of Rome, among the most rich and powerful men to ever live, asked his friends at his death bed if “he had performed the part well.” Seneca the Younger wrote an entire dialog about the misery of those trapped by their ambition, wealth and position—who having achieved their material goals, cannot give them up. A Stoic, Seneca argued that one was only at peace (wise) if one had the same peace when rich as when poor. A close contemporary in Galilee argued that the Kingdom of God and peace of the Lord could be found only in the heart and mind, and to worry not about material needs. Material things were the thorns and weeds that choked off the full expression of life—trust instead that what you truly needed would always be found.

But that is the golden cage of those with wealth AND honor. What of those who have left titles and responsibilities, but did so wealthy? Those with “fuck you” money? Perhaps even those who have hit Naval’s guide to wealth, and found ownership in something that scales, so they “make money while they sleep”? These should have the complete freedom of time and complete freedom of speech of the destitute, but instead with all their material needs fulfilled. No title, no board, no particular set of societal expectations because of a position they hold. Perhaps material needs fulfilled should be amended. Maybe “material needs fulfilled without encumbrance” is better?

But are they the only ones liberated by met material needs, and the only ones who can truly find peace of mind? The first rung on Maslow’s Hierarchy is met, and they have the time and freedom to climb the rest after all…

I am not sure even these are completely free. Ownership of a business that makes money while you sleep still encumbers you. At some point, you have to maintain the business or supervise those you hired to manage it. Certainly in “cancel culture”, self censorship is certainly encouraged (1). So there are scenarios where liberation from material needs by achieving them is not a guarantee of liberation from responsibility and worries, which may disrupt peace of/from mind.

If nothing else, I am certain that even those with “fuck you” money have mothers. Mothers who cajole them to visit, just like the rest of us.

Someone, something, somewhere, rational or emotional, obligates their time and their mind.

So should we instead think of probability? Are you more probable to have space, moments, for peace of/from mind if your material needs are met, or if you have no particular need of material things for your peace from/of mind?

Well, how often have you heard X is/was the “best time of my/your life”, and yet X is almost invariably a time when you had little financial wealth or security (like college), with no title or responsibility—but still had enormous time and freedom? Certainly, those describing such periods as “the best of their lives” have compared it to periods with greater material security, yet found their peace of/from mind greater when they did not have as much materially. Or perhaps did not need as much materially?

The situation reminds me of that great modern fable, a newly minted Ivy League MBA vacationing on a lake in Mexico. Our MBA meets a fisherman, and goes out with him one morning. The MBA is blown away by how successful the fisherman is at fishing—catches a big fish, every time. Our MBA runs the numbers excitedly that night, and races down to find the fisherman in the morning. “How would you like to expand and make more money?” says the MBA.

“Well, right now, I get up in the morning, and go fishing. I sell the fish, have lunch, and then have the rest of the evening for a bottle of wine with my family. What would I need to do to expand and make money?” asks the fisherman.

“If you take out a loan, you can buy another boat, hire another fisherman to man it, and double your income. You’ll pay the boat and the employee off in just one year!” says the MBA.

“And then?” says the fisherman.

“And then you can hire more boats and more fisherman. You’ll have your own small fleet in a few years of hard work!” says the MBA.

“And then?” says the fisherman.

“Well, you won’t be able to fish yourself for awhile. You’ll be busy running the fleet, boat maintenance, training and supervising your fishers to be as good as you are. But with all that effort, you’ll be able to grow your fleet to fish this entire lake, all day long!” says the MBA.

“And then?” says the fisherman.

“And then you’ll control the market for fish from this lake. You can expand, franchise your brand to other lakes, and get even more market share!” says the MBA.

“And then?” says the fisherman.

“Well, by then, you’ll be making so much money that you can hire someone else to run the franchises and the fleets. You will finally be able to relax, wake up in the morning, and go fishing whenever you want. In the evening, you’ll finally have the time to have a bottle of wine with your family,” says the MBA.

It’s not immediately obvious that material wealth and money are the sole means of getting time and freedom, health and security. Even in the modern era.

So what is the reconciliation? You have thousands of years of experience showing material wealth is often a trap, and an illusion of freedom, time, peace and happiness. Yet you also have thousands of years of experience showing the vast majority do not choose to give up material wealth or its pursuit, as that would make them less peaceful. History also shows successful sainthood is incredibly rare—so rare we venerate the few who actually make it.

Perhaps the lesson is that peace of mind is not a state of being, at least not in a permanent sense. Naval makes this distinction, separating “peace from mind” from “enlightenment,” or a permanent, lasting peace. Aristotle did not—hence, you only knew if someone was “happy” if they were until the very end.

So is the practical answer to simply find a way to seize more of those moments of peace from mind? Make yourself more “accident prone” for those moments of peace (as Jamie Wheal describes the process of capturing what he calls “flow”)?

After all, were Socrates, Plato and Aristotle always on? Were the Buddhas and the Saints? Or did they have moments when they were distracted by daily life, or not feeling well, and were, at least once, in their minds at least, disquieted? Did they have more moments of peace than most, or were their moments more peaceful, and that was the source of their mental clarity?

Have more/better “accidents” of peace from mind, and you make better decisions. Naval argues that is what is most practical about seeking peace and happiness in the modern world—improved decision making.

I wonder if Naval is arguing that is the path to virtue. But is that a chicken or the egg problem? Did the wise and peaceful, our Solomons and Saints, become virtuous first, and the harmony of their actions with virtue (as Aristotle argued above) give them less to be anxious or depressed about? Less chatter of mind because they already lived well, and thus more “accident prone” for peace from mind? Or do you blunder into peace from mind, and in that accidental reprieve, find the space and insight to make better moral decisions?

My suspicion is that being immoral or amoral is playing on Hard Mode. If the mind has more failings to recall, I think it less likely the mind will shut up long enough for peace to be found. Virtue must come first.

Yet I find it troubling to think of a perfectly immoral person. With no conscience to accuse them, is peace from mind actually easier for the sociopath to achieve? It’s not immediately obvious to me that it’s not. However, while they may be sociopathically, perversely okay with all of the damage they are doing to anyone and everything around them, they do not live in peace. They must constantly be creating chaos and violence to meet their own desires, at the expense of others. That is neither wise, nor peaceful, and will be prone to shattered peace and misery when someone finally prevents them from their crimes, or punishes them for them. So peace from mind/peace of mind/happiness as an internal state does not necessarily mean a wise or peaceful life. Conversely, one can imagine a Saint would still be at peace, a Saint, even when surrounded by Hell itself.

The well lived life is probably still one of virtue, and peace from mind.

So, “practically” speaking, is material wealth necessary by creating the right conditions, the “accident prone” for peace of mind? You can certainly make a case, as Naval and Aristotle did, that having material wealth helps. You can also make a case as so very many philosophers and proverbs have that having material wealth can also hinder. You can make a case that absence of wealth hinders and a case that absence of wealth may help. Or you can take the Stoic’s argument, and simply remove it as a variable with a clever change of definition—you are only at peace/happy if you have the same peace and happiness poor as you do rich.

However, most of those who are rich don’t choose to test their attainment of the Stoic’s peace by becoming poor. Likewise, comparatively few get the opportunity to test themselves rich.

So much for scientific empiricism with a well controlled trial leading us to an answer here!

I’m at a loss. All I have learned so far is that “peace” is, practically speaking, stolen moments—and I should give myself every opportunity for thievery. Virtue seems likely to increase the chances for these moments of peace. Renouncing material wealth may indeed be playing on hard mode—saints are rare, and I am unlikely to be among their number. But if material wealth is necessary for peace, then peace is always, to some extent, at the whims of fortune. And peace when wealthy is a false peace. Those who say that you are only at peace from mind if you have the same peace rich as you do poor are probably closer to the truth.

I will have to think about this some more though… I know this is short and unsatisfying, but if you have some thoughts on the topic, please reach out.

The Science of Aging

“Drink of this cup, and you will live forever.”

Such has been the allure of the elixir of life. The legends, whispered across millennia, claim that to dissolve the Philosopher’s Stone, the Great Work of the Alchemist, in wine and drink is to cure any ailment, reverse the sands of the time itself, and become forever young.

Turning lead to gold was just an economically useful secondary property of the Philosopher’s Stone.

Same for aging research. The goal is the elixir of life, a treatment that will reverse aging, or at least make for more functional aging. Truly make 80 the new 25, in physical and mental form and function. That success in this line of research would treat an enormous number of chronic diseases, release the burdens of elder care, and keep people productive and creative for far, far longer is likewise economically useful secondary properties.

So where are we on the modern alchemy, the Philosopher’s Stone that will treat aging?

For reasons entirely unrelated to turning 40 this year (shut up), I figured I would check in. Especially when Aubrey de Grey was making the podcast rounds, and claiming the effective intervention on aging was likely in the next 5-10 years. Despite running the SENS Research Foundation, Aubrey did not seem especially prone to hyperbole.

So I am by no means an expert in this field, so apologies now where I will inevitably fall short. But a few pulled papers later, and here is what I’ve got so far:

Why do we get old?

Not every organism seems to, at least physiologically. Temporally, of course, everything gets another year older. But some very small, relatively simple creatures like hydra and flatworms appear all but immortal. You’ll never see a hydra with a walker, or a flatworm with Alzheimer’s, barring some debilitating accident, infection, or lab experiment. They are functionally young forever. In larger, more complicated organisms, like humans, we see aging more clearly.

What’s the difference?

What happens in early life is the difference. In early embryogenesis, the new cells of the growing embryo are all pleuripotent, undifferentiated stem cells. That’s a fancy way of saying those cells can, and will, divide and differentiate into all the various tissues and organs. Some will become lung cells, for example. Others the brain. Others may become the thyroid, or adrenals. All of this specialization, while adding complexity, lets the organism do a lot more than species that are less complex. For example, by forming eyes, the organism can see. Ears, it can hear. Muscles, it can move. An immune system, and it can better resist viruses and single celled organisms like bacteria that might do the whole organism harm.

But this strategy only works if all of these differentiating cells, and all the new tissues and organs with specialized functions they form, work together in close harmony. The sum must be greater than the parts. Otherwise, you simply add complicated new organs, and the cost of their size and upkeep, with no benefit to the entire organism. Further, the growth and replication of the cells making up these different tissues and organs must be carefully controlled. They must get big enough to suit the function—but no larger. if the cells just keep on dividing and differentiating, you wind up with a liver that is too big, or muscles that rip their tendons off the bone and become useless, or just far too many cells in the body for the heart to provide with blood to survive.

So early life is pretty close to late life for simple organisms like hydra and flatworms. They are small, with relatively fewer cells per individual, and don’t have a whole lot of specialized organs and tissues. What they have works well enough to get by, and its easy to get the small number of cells and tissues to row together in the same direction. By contrast, you, a human being, have many more specialized organs and tissues. To get all of them rowing in the same direction, a trade off is made in early embryology. At some point, very early, your cells start selecting their “career path.” Cells that “choose” an organ-based career gradually lose the ability to turn into anything they want.

It’s similar to choosing your major in college, and then starting graduate school. As a freshman, any major is open. Then you take some classes, and your major choices are restricted a bit (unless you plan on staying in college extra years)—it’s now harder to become something else. Then you get a graduate degree, a masters or something similar. You are better at your chosen field—a better biologist, a more studied historian. But it’s hard to become a sociologist suddenly—you would have to blow everything up and start over as a freshman. So you start your career in your masters, and get a few years into it. You’re very good at your field—but just your field. Now turning around and becoming a farmer, for instance, takes lurching change. So difficult that few if any will choose to make it, and often not without significant external change (job loss, midlife crisis, etc.). Indeed, the older you become, the less likely, and less able you are to turn back and become something entirely different. An artist, perhaps.

In the same way, a cell in the embryo starts to become a liver cell. The further it gets to a mature liver cell, the less able it is to change back to the stem cell from which it came, and thus become something else entirely. Eventually, it becomes a mature liver cell. At that point, it’s very good at being a liver. But the chances that it will become skin, for example, are virtually nil. Not without a lot of external pressure, like re-wiring the cell completely with drugs, or response to major injury (which can cause cells to switch types to a limited extent, called metaplasia). So eventually, that cell just settles in and becomes a liver cell.

If that cell could continue to divide by itself, it would not function as well in its organ based job, and in the worst case, starts looking out only for itself and growing independently. This is cancer. So for multicellular organisms to survive with minimal risk of cancer, regeneration had to be confined to germ cells (sperm and egg) and stem cells.

In short, you age because as an embryo, some of your cells chose to become specialized organs so that the sum total of your cells could do more, and more amazing, things. To keep the team together, they all “agreed” to stop dividing for their own purposes, and settle in as a community of mature cells, each doing specific jobs as tissues and organs, to make you. The price of that choice was that your mature cells would age, get damaged by time and life, and need to be replaced by something else (since they can no longer divide by themselves, per their “contract” with each other).

So, a few “freshmen” are kept around the liver (and all other organs and tissues). These are “stem cells”, and just like you lose old professionals to illness, injury and retirement and need to replace them, so stem cells are on call to replace lost and damaged specialized cells. They simply divide, and then finish “liver college” (or whatever organ they are becoming). Over time, though, the “freshmen” too can be damaged by life, and lost. As you lose your pool of “freshmen,” your stem cells, it gets harder and harder to replace the old, injured, and retiring mature cells in organs and tissues.

And the inability to properly and fully repair the damage of life over time is aging.

The way that happens, at a molecular level, is control of TERT, telomerase reverse transcriptase. In cells that have chosen to specialize, TERT is down regulated. In stem cells, germ cells and most (if not all) cancer cells, TERT remains very active. What TERT does is protect the ends of chromosomes, which have a specific repetitive sequence of DNA called a telomere. There is some heritability to the length of telomeres, but the key thing to remember is they function as a sort of counter. Every time a cell divides, it loses one unit of telomere. If it loses enough, the cell will start eating its own useful DNA as it divides, and so enters an inert state called “senescence.” Every cell, regardless of its metabolic rate, can divide only so long as it has intact telomeres—and enough telomere units to spare at the end of its chromosomes. So on graduation from “liver college”, our differentiating liver cell agrees to shut off TERT. When it does, it is now stuck with the number of telomere units it has. So if the liver starts running low on “freshmen” (stem cells), and professional liver cells try to divide to repair the damage, they won’t be able to do it long before they are out of telomere units. When they are, ain’t no mo’ division. And no mo’ repair of the damaged liver, which now starts to look “old.” Chronic injury, taking out freshman and/or forcing the limited number of “fill in” divisions that mature liver cells can do in emergency, hastens the process of aging.

Also important to note that telomeres are damage prone portions of the chromosomes. Oxidative damage is a particular problem, and high oxidative stress can burn telomere units even without dividing, and reduce the regenerative ability of the cell and organ.

In contrast, the freshmen (stem cells), germ cells, and cancer cells keep TERT on. TERT will replace lost telomere units, so there is no significant penalty to these cells dividing. As soon as they spend a telomere unit to divide, they simply make a new telomere unit at the end of their chromosomes. The “switch” that turns TERT on or off is epigenetic. That’s a fancy way of saying that switch can be turned off and turned on—it’s not necessarily permanent. In fact, as you can guess, most cancers are cells which have found a way to turn TERT back on—and then picked up additional DNA damage that causes them to grow uncontrollably.

There are other ways to delay the damage and changes associated with aging on a cellular level. For example, dietary restriction (extremely low calorie diets) have been shown to prolong lifespan in many different species. Dietary restriction reduces insulin/IGF-1 signaling, reduces mTOR activity, and increases another class of proteins called sirtuins (more about them in a bit) and AMPK. All of that is a fancy way of saying that the metabolic load and profile of the organism is shifted, and in a way that delays the onset of aging—most likely by reducing chronic injuries to cells, tissues and organs. There are drugs that can affect those same changes (usually just one of those per drug). Metformin has been getting some longevity buzz—like dietary restriction, it reduces insulin and IGF-1 signaling by improving sensitivity of cells to insulin, so less insulin is needed to have the desired effect. Rapamycin is an mTOR inhibitor (in fact, mTOR stands for mammalian target of rapamycin). Sirtuin activity can be influenced by levels of its cofactor NAD+, and AMPK increases were actually a major focus of Soviet era studies to improve performance of power athletes.

In brief summary, aging happens because you are a complex critter, and your cells choose career paths to become various organs and tissues. To pay for their degree (and minimize your chance of cancer), they agree to turn off TERT, which means they have only a limited number of telomere units to spend dividing. Chronic injury can deplete your pool of stem cells, or “freshmen” you keep around with active TERT to divide and replace damaged cells in organs and tissues. Chronic injury can then force your “professional” cells to burn their last telomere units and become senescent (a special sign of aging we will cover shortly). Aging is thus a reversible process on a cellular level, characterized by a loss of the already limited regenerative capability of your body. To reverse the process, you must force reactivation of TERT (to create more stem-ness, or “freshman” like cells with more telomere units)—but the chief risk of that will be cancer. To delay the process, you can reduce chronic injuries to cells so you use up your regenerative reserve slower. We are in the early stages of identifying interventions that may help reduce chronic cellular injury.

Alright, still with me?

Good. Because I want to switch to the cellular “symptoms” of aging—in particular, cellular senescence. Normally, when a professional organ cell is damaged, but there are enough “freshmen” still around, that cell is removed entirely by apoptosis. The “freshman” then finishes organ college and fills the gap. When there are not enough freshmen anymore, and the cell is getting damaged, instead of apoptosis, the cell makes a different choice. This choice is senescence and it has consequences. Instead of getting removed, the senescent cell actually gets a little larger. The senescent cell is no longer as effective as a professional organ cell, and even worse, will “ping” for a freshman it never finds, sending out signals that promote inflammation (the aging of inflammation, also called “inflammaging” in their literature), angiogenesis and cell proliferation.

Yes, that’s right, it will damage its neighbors and try to encourage them to burn their emergency telomere units to replace it. Even though the senescent cell isn’t actually going anywhere.

Also, if you have heard of inflammation, angiogenesis and cell proliferation as processes involved in cancer—you’re right! That you have more time to have accumulated cell damage, with more depleted freshmen, and thus more cells in senescence with these cancer promoting signals getting spewed may help explain why cancer incidence tends to increase with age.

The inflammation has a very distinct “flavor” as well. IL-6 is a major cytokine involved in “inflammaging.” As you age, levels of IL-6 measured in the blood tend to go up. in fact, IL-6 levels correlate so strongly to aging that elevated IL-6 levels are predictive of impending age related disabilities like frailty, decreased walking speed, and overall mortality. “Inflammaging” is also especially adept at recruiting fibroblasts, for an inflammatory response that most closely resembles wound healing and scarring. That happens to be the same type of inflammatory response that tumors prefer for the normal support cells they will co-opt to help the tumor grow, and the type of response that seems to be occurring when cancer cells metastasize. All in all, probably not the best kind of chronic inflammation.

The main drivers of senescence are either DNA damage, or metabolic crisis. DNA damage is pretty self-explanatory. Ordinarily, the cell either repairs the damage, or if the damage cannot be repaired, removes itself by apoptosis. If, for some reason, apoptosis is blocked, the cell will go senescent. So you can think of senescence as a “Plan B” if a cell is damaged in a way that makes the cell think it might turn into cancer. While Plan B is useful to have, this particular Plan B comes at high cost. So high that there is probably a way to reverse senescence or at least repair the block to apoptosis that occurs naturally. Hopefully someone is working on that.

The other way senescence is triggered is metabolic crisis. In this situation, the cell notices that it is running out of energy. The sensor for this is AMPK (whom you may recall from just a few paragraphs ago—elevating AMPK may reduce symptoms of aging). AMPK is activated when there is not enough ATP around. ATP is simply the fuel that all cells run on—it’s the energy for everything. If AMPK notices there is not enough ATP, it activates pathways to 1) make more ATP from glucose and emergency energy stores and 2) make more mitochondria, the power plants of the cell, so more ATP can be made more quickly. At the same time, AMPK throws the brakes on the cell cycle and mTOR (also from a few paragraphs above). If the cell cannot generate enough ATP to make AMPK happy again, the brakes stay on too long, and that is a signal to the cell to go into senescence.

AMPK’s trigger to make MOAR mitochondria is important (2). One of the hallmarks of senescence is increased numbers and size of mitochondria. The problem in the fully senescent cell is that none of those mitochondria are working especially well. Age related damage to mitochondria and/or damage to mitophagy, the “power plant safety inspection” program of the cell, is broken. This leads to reduced ATP production, despite having more mitochondria around. To try to compensate, the broken mitochondria work as fast as they can—but they’re broken. They are not making ATP cleanly any more, and like an old, worn out factory are just spewing out dangerous byproducts out of their smokestacks. These byproducts are reactive oxygen species (ROS). Just like oxygen rusts iron, all of these ROS get spewed inside the cell and damage everything. DNA, proteins—everything “rusts.” This is why you keep hearing you should eat more anti-oxidants to “fight aging” and “prevent cancer.” To handle all the rust, senescent cells increase autophagy—basically, they have to constantly fix broken, rusty pieces. As you can imagine, a broken rusty cell, or cell having to spend most of its time fixing broken, rusty pieces is not doing its normal job as a lung or liver or brain cell well.

Broken mitochondria cranking as fast as they can also accumulate NADH, which is a different form of another molecule called NAD+. In fact, as you age, your levels of NAD+ in the blood decline. Part of that may be consumption, but there is also intriguing evidence that damaged mitochondria are just not processing it as well. More numbers of senescent cells as you age, with more mitochondria, and more broken mitochondria, per senescent cell may cause the NAD+ to get “trapped” in the mitochondria as excess NADH. This is bad news, because NAD+ is needed by a bunch of proteins called sirtuins (also mentioned a few paragraphs ago). They cannot use NADH—they have to have the NAD+. If more of the NAD+ is converted to NADH and “trapped” in crappy mitochondria factories, the sirtuins can no longer work. That’s bad news, because the sirtuins help with cell metabolism, apoptosis, senescence, and DNA repair. Sirt1 levels in the blood, for example, tend to decline as you age, probably due to age related NAD+ starvation as the NAD+ is increasingly trapped as NADH. Sirt1 is lowest in patients with neurodegenerative diseases like Alzheimer’s. Fortunately, it make take the loss of a lot of NAD+ availability to see much of an effect—the sirtuins may be able to make do with very little NAD+ around. Mice with an 85% reduction in NAD+ in skeletal muscle had only mild deficiencies in muscle mass and function into early mouse adulthood. But eventually a tipping point is reached, and that tipping point may be different in different tissues.

Lastly, having a bunch of broken mitochondria around in the cell appears to promote the release of mitochondrial DNA. When the immune system detects mitochondrial DNA in the blood stream, it tends to freak out a bit. This, too, may be a major trigger for “inflammaging”—and this chronic inflammation can in turn create more damage, causing more cells to reach a damage or metabolic crisis, and choose senescence. As well as force the pool of “freshmen” stem cells still around to deplete, either through use or damage to them.

All of this appears to become a vicious cycle for a senescent cell. There is either damage to a bunch of mitochondria or loss of the “safety inspection program” and damaged mitochondria accumulate. They don’t make ATP well, so ATP levels fall, triggering AMPK. AMPK causes an increase in mitochondria, but more and more of the mitochondria getting made are poorly inspected, heavily ROS producing polluters. These crappy factories trap NAD+ as NADH, so sirtuins don’t work as well, with loss of important protections of the cell’s DNA, apoptosis, senescence and metabolic pathways. In addition, the ROS rust everything, and the cell spends more time fixing rusty parts than its usual job. Broken pieces of the crappy factories leak into the bloodstream as mitochondrial DNA. This provokes inflammation, and the cell itself, now mired in a terminal loop of senescence signals also signals inflammation, angiogenesis and proliferation. As more and more cells get trapped in this cycle over the years, your tissues and organs “age.”

So to block this, you can do things like fast or reduce your caloric intake. As we mentioned, dietary restriction triggers a lot of the antitheses of these pathways. Dietary restriction appears to improve mitophagy, the “power plant inspection program”, reduces insulin/IGF-1 signaling, reduces mTOR activity (a “choose senescence” signal), and increases AMPK signaling to make more, but well inspected, mitochondria and increases sirtuin production. Note that none of this actually increases TERT, which directly increases the lifespan of your cells. But what it -will- do is reduce the amount of cells choosing senescence, prolonging the ability of your tissues and organs to absorb damage and regenerate. The hope is this -improves- longevity and how effective you are in older age, since fewer cells, organs and tissues should be stuck in senescence death spirals. If you like to eat, there are medications (as we mentioned) that are currently being investigated for anti-aging effects, all hitting different parts of this senescence spiral to try and slow it down. Some of the research on increasing AMPK via a very specific method of resistance training may overlap—just remember, this method was studied to improve athletic power (maximum force in minimal time) and has not, to my knowledge, been studied for effects on aging. Studies on these types of interventions, working on the biochemical pathways that are the biochemical symptoms of aging, is where Aubrey De Gray believes we will make progress in the next 5-10 years. As those trials move into humans, they will hopefully show beneficial effects reducing symptoms of aging.

That’s worth noting in bold. You can find some of these interventions, or very similar ones around already. Human clinical studies are not complete, and the full range of risks and benefits are not completely known yet. Be careful, and talk to your physician before trying any kind of supplement or medication.

And the effects may take years for you to notice anyway—besides the problem of an N of 1 study. There is no control “you” to get placebo and see how you would have aged without that supplement. That’s why we will need some controlled studies to get a better idea of how effective (if at all), when, and at what risks for these types of interventions.

Otherwise, for the true fountain of youth, you need to manipulate TERT directly to add “telomere units” to cells, and/or increase the pool of “freshman” available to you. This can be done by pharmacologic stimulation of TERT or adding more freshmen with something like stem cell injections. The risk of these type of interventions will be cancer, though, and so a lot more work on them will need to be done over the coming years as well to find best and safest practices for these kinds of interventions.

It may not turn lead into gold, but if any of this research leads into effective prolongation and functional aging, or even reverses the clock, it will make the golden years less leaden.

The Dummies Guide to CBD Oil

If you live in one of the states or regions that has legalized CBD oil, you have undoubtedly seen everyone and their brother advertising they “NOW HAVE CBD OIL!” Even gas stations.

This has led to questions, as a lot of people have no idea what CBD oil is, how effective it is, and what it’s used for. Because of the way the laws are written, you will see it called an oil, and generally not as a supplement or food. We’ll get into that. You will also see very few direct health claims, which is why there are questions about why CBD oil is suddenly everywhere.

So, this is a short version. As always, this is merely a summary of what I could find in the medical literature. It is not medical advice. I am not your doctor. You should consult your physician before beginning any drug or supplement regimen, as especially as there may be drug-drug interactions with specific medications you may be taking. None of these posts, including this one, are intended as diagnostic or therapeutic advice.

Now that we have made the lawyers happy, what the hell is CBD oil Paladin?

Glad you asked!

CBD oil is something of a catch-all for CannaBiDiol (CBD) and hemp oil products. Yes, it’s related to the marijuana. Hemp and marijuana are two strains of Cannabis stavia.

The marijuana strain has been bred for its high(er) [no pun intended] content of TetraHydroCannabinol (THC). This is a phytocannabinoid (class of molecule) produced naturally by the plant when smoked or ingested in purified edible (brownies, gummies, take your pick) that works primarily on CB1 receptors, which it activates. This in turn regulates the release of GABA and glutamate, a couple neurotransmitters. As you might be able to guess, CB1 receptors are found in high concentration in several regions of the brain, including those involved in emesis (puking), satiety, memory, and analgesia. THC is thought to provide pain relief, function as an anti-emetic (medical use is often in patients taking chemo where this is major side effect), and promote appetite. By report, it may function in an anti-anxiety capacity, and may impair memory. All of this is due to CB1’s job blocking release of GABA and glutamate. Glutamate is the major excitatory neurotransmitter in the brain, which may account for THC’s “chill” factor. GABA, on the hand, tends to relax neurons, especially with fear and anxiety, and may explain some of the well known paranoia associated with THC use, if GABA is significantly disrupted by CB1 receptor activation in the “right” places in the brain. GABA is also associated with learning and memory, and downregulation in the memory regions of the brain may account for the stereotypes that Cheech and Chong made a career out of, man. THC is also known to disrupt REM sleep, and chronic users may not be getting effective sleep at night, especially with use before bed.

The other strain, the hemp strain, of Cannabis stavia, is bred for the many uses of hemp, including paper, clothes, food, and a shocking amount of paraphernalia for the other strain of Cannabis. Hemp traditionally makes little, if any, THC. However, both hemp and the marijuana strain of Cannabis stavia produce CBD. CBD has a much more complex activity when taken. The molecule is known to block reuptake of endocannabinoids, which are the signaling molecules your body makes to activate CB1 for CB1’s usual function, as well as other receptors they can interact with. On net, the endocannabinoid receptors all work together to regulate immune function. When CBD blocks reuptake of the endocannabinoids, more of them are “stuck” in circulation, and will generally activate all the receptors endocannabinoids can reach, including CB1 (to some extent). However, it is FAR less potent at CB1 than THC is, and pure CBD does NOT have the “high” of THC as a result. CBD also has an indirect, but potent, ability to activate serotonin 5-HT1A receptors. The Joe Rogan fans in the audience may recognize that family, as the psychadelics DMT and psilocybin are active at a cousin of this receptor called serotonin 5-HT2A. Although in the same family, 1A and 2A are distinct receptors with distinct functions.

Sorry, dude. You are NOT going on the Hero’s Journey with pure CBD.

Serotonin 5-HT1A receptors are targeted by CBD, anti-anxiety medications, anti-depressant medications, and the “atypical” antipsychotics are partially effective at 5-HT1A. So as you can guess, there may be anti-anxiety and anti-depression effects of CBD based on its activity at the serotonin 5-HT1A receptor. However, activation of serotonin 5-HT1A may interfere with sleep and male sexual performance.

There are medications now available based on purified versions of these. For example, the nabiximols are non-synthetic mixtures of THC and CBD, in a roughly 1:1 ratio, and are used for pain control and muscle issues from conditions multiple sclerosis. Dronabinol is synthetic THC that has been FDA approved for use in anorexia in AIDS patients as well as nausea/vomiting in chemotherapy patients. Nabilone is a molecule approved in the 80s for treatment of nausea/vomiting in chemotherapy that has failed other treatments. Nabilone is lab-made cannabinoid that is structurally similar to THC. Finally, Epidiolex was approved in 2018. Epidiolex is pure CBD and is used to treat seizures in a couple rare seizure disorders after other medications have failed.

CBD was de-scheduled (taken off the list of controlled substances) in April, 2020.

The 2014 Agricultural Act in the United States defined “industrial hemp” as any Cannabis stavia with a THC content, on a dry weight basis, of less than 0.3%. “Industrial hemp” may be grown for “research” in the 2014 laws. The reason CBD oil blew up recently is the 2018 Agricultural Act, which made cultivation of “industrial hemp” (<0.3% THC) legal for any purpose. You no longer had to call it “research” and could just grow and sell at scale. BUT because there are drugs on the market that use CBD as an active component, the FDA ruled that you cannot call a CBD product a “supplement” OR legally add it to food. Hence, everything is a “hemp oil” or “CBD oil.”

And definitely, absolutely, unequivocally NOT a supplement or food, especially according to the manufacturer’s legal department. If you call your CBD oil a “supplement,” and their lawyers are in earshot, you are in for a correction, my friend! A prompt, detailed, and emphatic correction I say!

Any labelled health claims would also need a formal FDA submission. I’m not a lawyer, but there are suggestions that transporting CBD products across state lines for sale may not be entirely legal (at least not without formal FDA review), but prosecutions appear to be rare and generally unsuccessful.

Since CBD oils, if they meet the legal <0.3% THC limit, do not have enough THC to get you high, they are over the counter and do not need a prescription. That is, however, ABSOLUTELY enough to pop a drug screen positive, since THC may be present even in trace amounts. Your employer or prospective employer or sports regulatory body may not buy the excuse that it’s your CBD product, and not illegal, or against policy, use of marijuana. So there could very well be professional, personal and legal complications to use to consider.

It’s also worth noting that outside of the named drugs containing THC and CBD above, the “totally not a supplement” oils you see on sale are NOT required to be manufactured under “good manufacturing practices” (GMP) standards, with rigorous, FDA approved and inspected manufacturing.

As you can imagine, there is a wiiiiiide variety of what is actually in the bottle as a result. A review in 2017 found only 45% of 40 tested CBD oils were “accurately labeled” (90-110% of the concentration on the label) for their THC and CBD content. Slightly more products were likely to be less concentrated than claimed, but some were definitely over. The average over or under concentration versus the label was 29% (meaning the bottle contained a little under a third MORE concentrated CBD or a little under a third less CBD than what the label claimed). And that was just the CBD oils they tested. A whopping 75% of vape CBD products contained MORE CBD than the label claimed. And not a little more. Median deviation was 67% from what was on the label. It’s worth mentioning at this point that vaping has been associated with a serious form of lung disease in some users, and in association with some CBD products in some cases. None of the CBD was concentrated to a level concerning for serious toxicity, but 21% of all the CBD products they tested had THC present. In some cases, enough THC to get someone high (especially if a kid got into the bottle). On the flip side, about 1 in 4 products they tested had less CBD present than the label claimed. In some cases, hardly any CBD at all, basically turning it into placebo. This is not a new problem. A number of manufacturers have received warning letters from the FDA going back as early as 2015 for not containing the amount of CBD claimed on their label.

Caveat emptor.

If you do decide to pick up CBD products, you may want to consider the Mayo Clinic’s modified Basic Dietary Supplement Collaboration Checklist:
1) Does the product you are considering meet the following quality standards (depending on country of origin)?
a) Current good manufacturing practices (GMP) from the US FDA
b) European Union (EU), Australian (AUS) or Canadian (CFIA) organic certification
c) National Science Foundation (NSF) International certification
2) Does the company have an independent adverse event reporting program?
3) Is the product certified organic or ecofarmed?
4) Have the products been third party tested, by batch, to confirm THC levels <0.3% and no other contaminants like pesticides or heavy metals?

In fact, because of persistent labeling problems among the CBD manufacturers, the Mayo Clinic recommends use of products imported from Europe, where hemp regulation is more established and the cut-off for THC more strict (must be less than 0.2% by dry weight).

Other product notes. You will see “hemp seed oils” marketed as well. A hemp seed oil comes from the seeds of Cannabis stavia, and does not contain significant amounts of CBD or THC. It’s mostly omega 3-fatty acids. So don’t expect any THC or CBD benefits or activity from “hemp seed” products.

Alright. So that’s what CBD is. Next major questions—is it safe? Does it work?

The best safety data for CBD comes from studies of epidiolex, which is pharmaceutical grade pure stuff. Before starting epidiolex, your doctor should get baseline liver function tests and test again at 1, 3 and 6 months after starting use. In studies of epidiolex, up to 17% of patients experienced an increase in liver function tests, indicating some liver damage may be occurring. The dose of epidiolex may need to be adjusted down if there is evidence of this liver damage while taking the medication. Other common side effects included infection (25-41%) with viral infections specifically in 7-11% of people taking epidiolex. Anemia was seen in up to 30% of patients. Otherwise, sedation, lethargy, and drowsiness were most common (in a little under 1/3rd of patients). Decreased appetite, weight loss, and diarrhea were seen in about 20% of patients. You can absolutely be allergic to CBD (and epidiolex) and should not use the products if you are.

When taken as epidiolex, CBD dosing starts at 2.5 mg/kg twice daily. So a 165 lbs person would aim to start at about 187.5 mg of CBD, twice per day, or 375 mg per day total. After the first week, the dose is doubled to epidiolex’s 5 mg/kg twice daily maintenance dose. So again, our 165 lbs person would take 375 mg of CBD, now twice per day, or 750 mg per day total. Epidiolex has a maximum maintenance dose of 10 mg/kg twice daily, and has been safely used up to 20 mg/kg, albeit with an increase in side effects mentioned above. This is consistent for our 165 lbs hypothetical person for other publications looking at CBD, where 300 mg/day was used for up to 6 months pretty safely, and doses of 1200-1500 mg/day were safe for up to 4 weeks. You should check the label for any CBD product you might use, if not using prescription CBD like epidiolex, for its CBD content and keep these numbers and any label recommendations in mind. Again, discuss with your physician before trying any new supplement or “totally not a supplement” oil. There may be significant risks in pregnancy (not much is really known for sure in use during pregnancy), and I would recommend you check out the epidiolex website for a full discussion of all potential side effects, especially in pregnancy. THIS IS NOT MEDICAL ADVICE.

And again, remember that a shocking amount of the labeling on those “totally not a supplement” CBD products is WRONG in terms of how much CBD is in it.

In terms of efficacy, probably the best resource is Whiting et al.’s “Cannabinoids for Medical Use: A Systematic Review and Meta-Analysis” published in the Journal of the American Medical Association (JAMA), 2015, 313(24) : 2456-73.

The balance of clinical trials suggest use of cannabinoids is effective in pain control versus placebo. More patients taking cannabinoids experienced a 30% reduction or greater in pain using them than placebo arms. However, a MAJOR limitation is the authors were looking at ALL cannabinoids, including THC studies. Most of the published pain studies have been with nabiximol, which as you recall from above is a 1:1 mix of CBD and THC. The single study with the BEST effect on pain control was actually with smoked THC (marijuana). So even though they found evidence in favor of cannibinoids, it is not at all clear how much of that, if any, was due to CBD by itself.

Indeed, for pain control, the authors gave this only “moderate” evidence in favor of CBD and THC. This means they believe that additional research is likely to shift the results a bit (could be better; could be worse), and may change their recommendation.

More recent reviews by Argueta et al. (Front Pharmacol. 2020; 11: 561) and Inglet et al. (Ann Pharmacother. 2020 Jun 2) confirm some evidence for CBD effectiveness against pain. Again, most of the studies are with nabiximol, so confounding with THC cannot be excluded. But Argueta et al. has at least some small, CBD focused studies showing some efficacy in a few of them. I would not call any of them strong evidence, and none of the other authors mentioned do either.

Inglet et al. and Whiting et al. both agree that there is limited evidence in favor of effective treatment of nausea and vomiting (associated with chemo), seizure disorders, and multiple sclerosis associated muscle disorders. Again, a LOT of that data includes THC containing products, so separating the effects of CBD specifically is tough to do.

That said, at least for seizure disorders, epidiolex has proven CBD specific effectiveness.

So, the TL;DR of the story?

CBD is another chemical made by the same plant that brings you marijuana. CBD, by itself, does not get you high and works through a slightly different set of receptors. There is a risk of side-effects from CBD, with drowsiness/lethargy/sedation being most common, although a good number of patients get lab evidence of some liver toxicity. When taken in prescription form, CBD requires baseline liver tests, and tests again at 1, 3 and 6 months to look for that liver damage. There is also a very high risk that the over the counter versions of CBD may be mislabeled for the amount of CBD (and THC) that is in them. The legally allowed, but small amount, of THC in many CBD products can and will pop a drug screen positive. There is some evidence that CBD may be effective in reducing pain, and the prescription form, epidiolex, is proven to be effective in treating some rare forms of seizure disorder. Caveat emptor, and talk to your doctor before starting use, especially if you are, or could become, pregnant while using.

The Poor Damn Bees

Yeah, the poor damn bees. As if colony collapse disorder wasn’t enough, now, this being 2020, Apis mellifera, the western honey bee, now apparently has murder hornets to contend with too.

I have to admit, I thought the bees were starting to rally back from colony collapse. So I was surprised to hear Paul Stamets, famed mycologist, out on a podcast claiming that “this is really an all hands on deck moment.” He also happened to be touting a new product he had developed called the “BeeMushroomed,” and we’ll get into that in a moment.

But I thought it was worth a check on the bees.

Apis mellifera dominates agricultural honeybees worldwide. Although slightly more aggressive than its eastern cousin Apis cerana, the western honeybee, Apis mellifera, produces much more honey per colony. Because of this, even in places like Japan, the western honeybee is the most common bee in apiaries. An enormous range of flower and food crops worldwide are pollinated primarily by the honeybee. The tireless works of a bee colony can collect an enormous amount of pollen over a range of several miles from their nest. If there was a catastrophic loss of Apis, it is not an exaggeration to say that food security worldwide would be significantly threatened.

The primary threat to Apis mellifera is a mite from East Asia. This is the Verroa destructor mite, the TRAVELLER, pictured above. The V. destructor mite (and yes, that is its actual name) presents a couple of threats to infected bee colonies. First, an adult female mite attaches to a bee and enters the hive. Once there, it finds a brood cell and hides. As soon as the worker bees cap the cell, the adult female starts laying eggs, which infect the larva growing in the cell with the mite. The mites preferentially infest cells growing male drone bees. The males take a few extra days to emerge from the cell, giving the mite more time to work. When the new bee emerges from the cell, the mite babies are already attached and feeding, and start to spread within the colony. In fact, their goal is now to hop onto a nurse bee, who tends the brood colonies, so they can infect more brood cells. The mite itself hides on the underside of the bees, and feeds on the bee’s fat (yes, they have fat–I was today years old when I learned that too). That fat is used by bees for energy, making the complicated hormones that control the functioning of the hive, and the bee’s immune system, and so makes the individual bees to weak to work as well, in a hive that no longer communicates as well, and is more susceptible to disease.

Disease is an even bigger threat from the mites than the mite itself. Varroa destructor is a carrier of at least 10 important bee viruses, chief among them deformed wing virus (DWV) and varroa destructor virus-1 (VDV1). The combination of the mites’ parasitism on the bees, especially weakening the immune system for these viruses to wreak havoc, is what causes colony collapse disorder.

As colonies overrun with mites and viruses grow weaker, other bee colonies will now attack them. When they do, they pick up the mite, allowing the mite to spread to new host colonies to infect.

Bee agricultural practices also bear some blame. To maximize honey production, bee colonies are allowed to grow as big as possible. The larger colony size makes it easier for mites to slip in, lost among the shuffle, and a LOT more brood cells to potentially infect. Apiaries also try to prevent swarming, when a new queen emerges and leaves with a group of worker bees to go off and form a new colony. They would much rather keep that queen and new colony, thank you very much. But preventing swarming to maximize a producing colony reduces spread of bee genes, and a chance for some of the bees to “get out” before an infestation of the mite takes over. Lastly, a lot of hive equipment gets re-used among different colonies in the apiary, and can be a vector for the mites if they get on it while a diseased colony is being worked on.

Apis cerana is far less affected by the Varroa destructor mite, having about a century’s worth of experience the parasite already. Apis mellifera, on the other hand, is only just meeting the mite, and does not have a high degree of immunity. The chief defense of the eastern honeybee to the mite is a higher degree of “grooming” behavior. The eastern honeybees have adapted to do more frequent “mite checks” of each other, and pull off the parasite when they find them. They are also able to “sniff out” brood cells with mites growing in them and either entomb them so they never hatch, or crack them open, pull out the baby bee, and kill it and all the mites growing on it.

So the good news for Apis mellifera is that control of the mite can be done. The bad news is that the defenses of their eastern cousin are not as natural to Apis mellifera. Yet. But the bees have us on their side too, and we have some technology to chuck at the mite while natural selection takes hold to select for more mite resistant strains of mellifera. Working in our advantage is that bees have an astronomical genetic recombination rate, so defenses can emerge quickly. The down side is that without constant selection pressure, they might also disappear very quickly too.

As man is want to do, our first strategy was to chemically treat the colonies to kill the mites. There are pesticides relatively safe for bees that are bad for the mite. The problem is that the pesticides are only about 95% effective. The 5% of the mites that survive are highly resistant to the pesticide, and it has not taken the mite long to become completely resistant to these treatments. But new treatments are on the horizon. I mentioned Paul Stamets and the “BeeMushroomed” feeder above. This is device that anyone can hang on their lawn that will attract bees. But its feeding mixture also contains a number of fungi that have shown in vitro activity against some of the main viruses carried by mite. In caged bee laboratory conditions on actual bee colonies with and without this fungal BeeMushroomed treatment, colonies that were treated by “BeeMushroomed” showed a significant reduction in viruses like DWV.

The limitations of this study are significant though. First, and most significant, they introduced the viruses, but not the mites. We have no idea if “BeeMushroomed” is effective against the Varroa mite, and the mite is the bigger problem. If you can chase the mite off, the chance that the colony will need anti-viral treatment is minimal. Second, while the reduction in the viruses with treatment was significant and nominally impressive, it’s not clear if this kills enough virus to be “clinically effective” and stop colony collapse disorder. It may help. But it would have been nice to see “next generation” testing in another round of laboratory tested bees with the surviving viruses and/or in vitro testing of surviving viruses to see if the small amounts of virus that made it are now resistant to “BeeMushroomed.” If they are, “BeeMushroomed” will not be effective against the viruses for long. Third, the colonies were fed the “BeeMushroomed” mixture fairly directly. We don’t know if bees encountering the “BeeMushroomed” device hanging in your backyard would “eat’ an equivalent dose. If they “underdose” by not eating enough, they may not stop the virus, and worse, like underdosing an antibiotic, would actually breed resistance in the virus by constant, sub-lethal exposure to the treatment. In fairness, this does show that directly feeding it to bees with equipment commonly used in hive feeders reduces replication of a number of nasty viruses. I don’t know how often apiaries feed their bees like that, or if this is enough to persuade them to use this product that way. Lastly, long term studies (or at least a couple growing seasons worth) looking for effects on the bees themselves, when treated with “BeeMushroomed”, for honey production, behavior, other health risks, would be useful. Just because the fungi are natural doesn’t mean they are completely safe for the bees, and verification of safety would probably be appreciated by the apiary community. Primum non nocere—especially if the threat to the bees is so grave it is an “all hands on deck” moment. Stamets et. al.’s sole publication on the idea behind the “BeeMushroomed” is “Extracts of Polypore Mushroom Mycelia Reduce Viruses in Honeybees” in Nature Scientific Reports 2018 8:13939 and appears to have been a fee for contract research service for the caged bee testing portion funded by Fungi Perfecti, maker of the “BeeMushroomed”, and used as the basis for a patent filed on its behalf. So while it is a very interesting idea for anti-viral control of some of the viruses introduced by the mite, I am not certain enough work has been done to prove its usefulness just yet. I would be curious to see what the bee hobbyists think of it, but a quick Google search didn’t hit on anything obvious.

Regardless, there is still hope, and hope that does not require drugs. Apart from mandatory inspection for evidence of mite and virus infestation (and required isolation and control measures if they are found) in many places in the world, there are a number of locations worldwide that have identified colonies of Apis mellifera that have evolved resistance to the Varroa destructor mite.

From Russia, to Europe, to Brazil to the US, the western honeybee is fighting back. As you can imagine, the most popular strategy has been to ramp up “grooming” and “hygenic” behavior to levels similar to their Eastern honeybee cousins. These survivor colonies of mellifera find the mite better, and also hunt down and destroy infected brood cells. Like the eastern honeybee, the mites also seem to not reproduce nearly as well in the brood cells of these bees. Some slightly more novel strategies have emerged too. For example, one strain of survivors in New York gets by reducing the size of the colony. A smaller “tribe” is less likely to get infected, and more easily inspected for by its sisters for mites, making the mite less able to infect and spread within colonies of this strain. Several other survivor strains have shorter development times for young bees. They actually grow too quickly for the mites in infected brood cells to mature and mate, and the mites lose their chance. Interestingly, most of the resistance has been found in “wild” western honeybees. But these resistant strains can be cross-bred with their “farmed” cousins to more quickly spread mite resistance traits.

Humanity’s technology is stepping in to accelerate that process as well. Complete genetic sequencing of both the mite and resistant bees has identified a number of genes that may correlate to resistance. Most of them appear to be in antenna and smell receptors, and probably associated with “grooming” and “infected brood cell detection and elimination” behaviors. This kind of genetic testing may allow the bee industry to select queens with lots of resistance genes for cross breeding, and spread mite resistant strains more quickly. There is also a protein-based test, where beekeepers can send some bee antenna in for a lab test. This lab test looks for proteins known to be associated with mite resistance, so again, bee keepers can pick and cross breed those colonies with better mite resistance, and get all of their producing hives less susceptible to the destructor.

So if colony collapse disorder appears likely manageable, especially if we can boost the selection of mite resistant western honey bees near term, what about the murder hornets—2020’s letter of love to the western honey bee?

Again, the headlines screamed of impending bee doom, as “a single murder hornet can kill 10,000 bees by itself!” The hornet is too big, its armor too strong! THE BEE’S STING IS USELESS AGAINST THEM!!!!

That’s cool. Again, Apis cerana, the eastern honeybee, lives where the murder hornets come from. The eastern honeybee may have 99 problems, but the murder hornets generally aren’t one. Also, the western honeybee is grown already in places where the murder hornet is found—and grown successfully. While the murder hornet is a little more successful against them still, both the eastern and western honeybee have been observed using similar anti-hornet strategies.

So the eastern honeybee has two basic strategies to deal with murder hornets. One is to simply have its hive guarding bees display a specific wing behavior. This is thought to do two things. One—warn the hive that murder hornets have been spotted. And two, it lets the murder hornets know they have been spotted. Turns out murder hornets are largely interested only in sneak attack on the bees. This is probably because of basic strategy number two. Even though, indeed, a murder hornet is way too big and its exoskeleton too thick for a bee to take it one on one, the bees don’t fight them one on one. When attacking the hive, the hornets are massively outnumbered. The eastern honeybee, and some western honeybee strains, immediately surround the larger hornet. The don’t bother with the sting. Instead, they literally coat the invading murder hornet in a rolling ball of bee death, and all the bees start furiously flapping their wings. The sheer body heat from all of the bees roasts the trapped hornet alive. Slowly. Inexorably.

Nature don’t play.

It’s not a nice way to die, and why murder hornets appear to leave honeybees alone when they know the bees are ready and waiting for them.

Now, is a western bee colony already heavily infested by mites and viruses likely to effectively mount this defense? Probably not. And not every western honeybee strain has quite caught onto the fact that they can handle heat much, much better than a hornet can. Only a few strains in the literature have been seen forming Voltron to murder murder hornets in a bee ball of doom. The others try to fight valiantly in one on one, stinger based battles with hornets and that is not a game the bee is going to win. So given the prevalence of mite susceptibility, the timing of the introduction of murder hornets to the western hemisphere isn’t great. The hornets have a better chance of finding mite weakened hives that cannot fight back as well. But, only a few murder hornets have been spotted in the Western hemisphere, and there are active programs to find and destroy murder hornet nests. Efforts to quickly breed and spread mite resistance based on the already mite resistant western honeybee strains can be replicated to find and test for genes and traits in western honeybees to both resist mites AND form swirling balls of hornet death.

The bees have a couple big challenges, and are still in the midst of fighting them. But natural selection has already given the bees the tools. The trick now is using human biotechnology to help our little pollinating friends spread tougher bees far, fast and wide, and these challenges can be, and likely will be, met.

So be concerned, because any threat to our bee buddies is also a threat to our food supply. But at the same time, recognize that these are tough girls who have been around a loooong time. They are already finding ways to win, and we are hard at work on ways to help them win quicker.

PREDICT 2 Update

The results from the “personalized” nutrition study, PREDICT 2, that I participated in as a research subject are back, and now comes the good part. In short, this is the study that used standardized meals with continuous blood glucose monitoring, plus periodic blood tests, and a stool test, to see how you, personally, react to various loads of macronutrients and timing of your eating. I posted on it before here and here. They have a nice little report on your personal results, and access to the Zoe app, which lets you track your foods based on how -you- respond to them. The app will also show suggested meals at various likely impacts on you, and will let you know as you are tracking food if you are eating too much sugar or too much fat in a particular meal. Zoe will also recommend -when- you should next eat, to space out fats especially so they have time to be fully processed by your body. The app not only calculates a score for each food, but also for each meal or snack (if snacking on more than one food). You can also enter foods just by scanning the bar code. All in all, although still in an early form, the app works pretty well. If you have used “My Fitness Pal” before, you will be familiar with the food entry and scanning system.

So it turns out my ability to handle sugar is phenomenally strong for my age, but my ability to handle fat is only a little above average. I also discovered that diary is better for me than I thought (based on fat content). As I have been playing with the app and tracking, it turns out my “go to meal” at restaurants, the Cobb salad, is an absolute disaster for me. Time to find a new go to. Otherwise, foods that score well for me and likely to score well for others are unprocessed foods. There is a high emphasis on fruits and vegetables (although some are better choices than others, and may have different individual recommendations), unprocessed food, and chicken/turkey/eggs/seafood instead of pork/beef.

The next phase of the study is to follow a 4 week plan alongside the study team. They are tracking for subjective energy levels, hunger and measured weight loss. The first two weeks you eat only personal superfoods—foods with a high personal recommendation (Zoe score 75+). The idea here is to “reset” over the first two weeks. The next two weeks you are asked to have a high average day score (75+ or better). This means you can include some less recommended (Zoe score 50-75 or so) foods, so long as your daily average comes out to 75+. You can do that either by sticking to vast majority superfoods (75+) or having super healthy meals (high Zoe average) “outweigh” one less healthy meal (Zoe score 50-75) for the meal. There are weekly check ins for weight, mood, energy levels and hunger. I believe the hope is for a bit of weight loss in their first four weeks, without leaving you feeling hungry all the time, drained of energy, and irritable like many crash diets can.

I’m going to go one step further, and track it here for you. I have a Whoop strap, which measures sleep, calories burned per day (via heart monitoring) and combines heart rate monitoring and sleep to calculate your personal “percent recovery” every morning. This can help me keep track of “energy level” (Whoop recovery score), while helping me control for influence of sleep and calories burned on any weight loss that might happen. I’ve also got a Vitagoods scale, which not only tracks weight, but uses electrical resistance to estimate % body fat and % muscle mass. I will also use the Zoe app to track the “macros”: calories in on the study, and protein/fat/carb g per day average. I will consider Zoe a personal success if body fat % gets lower (without drop in % muscle mass), with or without weight loss. I plan to extend the “eat for a 75+ daily average score on Zoe” portion beyond the last two weeks, and run it out another 4 (8 weeks total). I’ll post the weekly numbers here.

Note: I also use intermittent fasting on the regular (I don’t eat breakfast, and eat pretty much from lunch through dinner only).

So to start, here is baseline after a dessert heavy holiday weekend (knowing the “reset” was starting today!):

Whoop Data:
Last week’s average daily strain (29 Jun to 5 Jul): 11.2
Last week’s average daily calories burned: 2,226
Last week’s average percent recovery: 57%
Last week’s average sleep performance: 76%

Vitagoods Data:
Weight: 173.8 lbs
% Body fat: 19.3
% Lean mass: 39.3

Calories and Macros In: To be collected starting this week.

Sure, it’s an “N” of 1 look for right now, but if it works for me, it’s a sneak peek on something that might just work for you too… Either way.

Zen in the Time of Coronavirus

(1) “Cancel culture,” and the witch hunts of the digital mob, can only create Pharisees. Those who say the right lengthy prayers, perform the right and approved rituals, condemn those who violate or do not participate in the same or believe the exact same rigid rules they follow and of course show contempt for those automatically deemed defiled by the nature of their work, or foreign status. The Pharisees were justly condemned, both for using their rules for their own selfish gains, and enforcing them even when a greater mercy or good could have been achieved (i.e. healing a cripple on a Sabbath, or even forgiving sins at all). Most especially, the Pharisees were ju dged hypocrites—since their hearts could be -far- from the purity of their words and rituals. As long as they kept saying the right things, and doing the right rituals, though, their position in society was secure, and their actions could stay far from their true thoughts. This is a miserable way to live, and far from the harmony of thought, being (soul) and action that the ancients defined as “virtue” from time immemorial. It’s also bad for society as a whole. You are far better with freedom of speech—so you can -know- what people are -really- thinking. And know who you need to persuade to change for the better, if their thoughts and deeds are not virtuous.

(2) You can read Pavel’s “The Quick and The Dead” for Soviet research in power sports to trigger AMPK specifically to force production of more mitochondria in muscles

Tagged Aging, Aristotle, Bees, CBD Oil, Happiness, Mites, Money, Murder Hornets, Naval, Peace, Peace From Mind, Peace of Mind, PREDICT 2, Wealth, Zoe