Exercise mimetics, fasting mimetics

I have spent a lot of time following the latest research on all sorts of interventions to increase lifespan and healthspan. I am now ready to say that virtually all this time has been wasted.

I guess it hasn’t technically been wasted, in that I’ve come to understand the latest research, and that’s of some value. But when it comes to choosing interventions that might help me, it turns out there’s nothing new beyond the obvious healthy lifestyle recommendations of 20 or even 30 years ago.

There are a bunch of chemical interventions that are interesting—they have definitely been shown to increase healthspan and lifespan in animal models, and have had some very promising results in humans as well. However, it is becoming clear that virtually all of them are either exercise mimetics or fasting mimetics—drugs that activate (some of) the metabolic pathways activated by exercise or fasting.

From a public health perspective, perhaps this is of some interest. Given a population of sedentary people with poor diets it’s easy to foresee a mix of these drugs delaying mortality and morbidity—people will live longer, and during their extended lifespan they’ll have less disability, less illness, and require less medical care.

From my perspective though, it’s completely uninteresting. I would much rather just exercise than take a drug that provides a subset of the benefits of exercise. Similarly, I’d much rather just eat good food than take a drug that simulates some of the effects of doing so.

Do you want to live a long, healthy life? Here’s an plan for you:

  1. Eat a whole-food diet that’s low in sugar and refined carbs. Try to include a couple servings of salmon (or other fatty fish) per week.
  2. Finish supper at least 3 hours before bedtime, and make sure there’s at least 12 (preferably 13 or 14) hours between the end of supper and the start of breakfast.
  3. Get at least 2 resistance workouts a week where you exercise your big muscles (glutes, quads, hamstrings, pecs, traps, lats) until they are briefly very tired.
  4. Get at least 2 endurance workouts a week where you spend an hour or so exercising at a pace that’s a little more intense than a brisk walk.
  5. Get 1 workout a week where you raise your heart rate to 80% of its maximum for 30 seconds, rest for 30 seconds, and then repeat for a total of 10 rounds.
  6. Spend some time outdoors at least several times a week.
  7. Sleep until you wake up naturally almost every night.

That’s it. Unless you are sick with a diagnosed condition for which there is treatment, I very much doubt there is anything modern medicine—or even bleeding-edge longevity research—can do for you that you won’t get from this plan.

I’m sure my brother is very amused that it has taken me this long to come to this conclusion.

Hang out with healthy biomes

Everybody knows that you come to be like the people you hang out with, and most people understand that you can take advantage of this to improve your life. If you want to be more productive, hang out with productive people. If you want to be an intellectual, hang out with intellectuals. If you want to be healthy, hang out with healthy people.

I rather suspect this last is something hardwired in our brains, probably explaining part of the stigma faced by people who are disabled or disfigured. Probably strongly selected for in circumstances where infectious disease is a major cause of mortality.

I have always assumed that this is primarily mediated by lifestyle, with the shift largely produced by adopting pieces of the lifestyles of the people you hang out with. Hanging out with people who read a lot normalizes reading a lot. Hanging out with runners normalizes taking up running.

It should have been obvious—maybe it is obvious to everybody else—but it only recently occurred to me that a large part of this may well be mediated by microbiomes.

Your microbiome will shift to converge with the microbiome of people you hang out with. (Of course, theirs will also shift to converge with yours.) If you share meals with someone, your intestinal microbiome with shift toward theirs—probably more so and more quickly if you share a kitchen, utensils, or food prep tasks, and probably more so yet if you share a bathroom. If you share a touch with someone, your skin microbiome will shift—again, more so and more quickly if you share a bed with them.

Actually, an anecdote on this last: When I met Jackie she had a fungal infection of the skin that she’d picked up in India, and that had persisted for years. She treated it with tolnaftate, which worked adequately to knock it down when it became annoying, but had not cleared it up, either in India or after she came home. However, a few years after we got married I noticed that it seemed to be gone. With no evidence whatsoever, I’m inclined to take credit for this, figuring that my skin microbiome contributed useful organisms that her skin microbiome integrated in a way that eventually let it displace the fungal organisms.

So far, all the efforts to find an “optimal” microbiome have foundered, probably because the problem is intractably complex, being inextricably connected with the genes of the host, multi-generational epigenetic history, the immune system (and its lifetime history of chemical and biological insults), along with all the obvious factors—what organisms initially seeded the microbiome, history of antibiotic use, diet, etc.

Because of that, I’m much less interested now in interventions such as probiotics. More and more I’m inclined to prefer what used to be pretty obvious: Trust your immune system to cultivate a healthy microbiome (and hang out with healthy people to give it a little extra to work with).

Off all meds

For years I took drugs for high blood pressure, and for almost as long for allergy symptoms. This post is just to mention that going low-carb has gotten me off all of them.

I got off the allergy meds first. I got on them gradually. For years I said I didn’t have allergies. Then for years after that I said, “Well, for a couple of weeks in the spring and a couple of weeks in the fall, I get a little snuffly.” Then I started being snuffly all spring and all fall. At some point I started taking antihistamines (Claritin seemed to provide the most symptom relief with the least amount of drowsiness), and then at some point I started taking Nasacort as well, to manage congestion that otherwise made it impossible to breathe through my nose.

I initially went low-carb specifically to get off the allergy meds. Without the Nasacort I often had to breathe through my mouth—unpleasant, but also a genuine safety hazard while eating.

It worked, and it worked very quickly—in about three days I was off the allergy meds.

Getting off the blood pressure meds (lisinopril) took a while longer, although I saw improvement almost as quickly. Just a few weeks after going low-carb, prompted by some postural hypotension, I cut the dose I was taking first by half, and then by half again.

I remained on that one-quarter dose for about a year. But two months ago the postural hypotension returned. So, in consultation with my doctor, went ahead and stopped taking the bp meds altogether.

I’m especially glad to be off the Nasacort, which although supposedly a topical steroid is known to have systemic effects in at least some people. Claritin is probably not associated with Alzheimer’s (because it is non-drowsy), but people haven’t been taking it long enough to be sure. I’m sure glad I took the lisinopril—I don’t want to think about the shape my heart and kidneys would be in now if I’d had uncontrolled high blood pressure for the past 25 years—but I’m glad to be off it now.

I no longer have to deal with the common side effects (or worry about the rare side effects). I no longer need to make the monthly trip to the pharmacy. It’s going to make things like traveling easier—not to have to carefully pack up the necessary doses for each day of travel, not to have to worry about getting separated from my meds.

It’s a really nice feeling.


Letter to Rodney Davis on the Affordable Care Act

Below is the letter I just sent to my congressman.

I undoubted spent way more time drafting this letter than it was worth. I have no illusions that my congressman will read it and be swayed by my logic. As a practical matter, the best I can hope for is that someone on his staff will look at it carefully enough to add one tick to the column for “constituents opposed to repealing Obamacare.”

And yet, I think it was worth the effort I put into writing it—partially for my own benefit, as a way to clarify what I thought the most important points were, and partially for any local folks who might read it and be moved to weigh in with their own thoughts on the matter.

The Honorable Rodney Davis
1740 Longworth House Office Building
Washington, DC 20515

Dear Congressman Davis:

I am writing to urge you to preserve three key elements of the Affordable Care Act, which Speaker Paul Ryan’s “A Better Way” agenda does not protect: that policies cover the full range of essential care, that coverage be available at standard rates regardless of preexisting conditions, and that credits be available to help lower-income people buy health insurance.

With the Affordable Care Act’s rules, it’s possible to buy an insurance police and know that a full range of important care is covered. The “more choices” supported by Speaker Ryan’s plan would mean that people could “chose” to buy insurance with incomplete coverage. I have first-hand experience with how much work it is to analyze and compare insurance policies, trying to read between the lines to see what essential coverage is missing. The result of the Speaker’s plan would be many people who thought they were getting a good deal on their insurance would face bankruptcy because of hidden gaps.

With the Affordable Care Act, the last four years have been wonderfully free of the anxiety that any illness could turn into the “preexisting condition” that would make health insurance unavailable. Speaker Ryan’s plan to condition this on “continuous coverage” is a poor substitute. Sometimes people suffer a financial catastrophe and are temporarily unable to afford to maintain their insurance. It is terribly cruel to compound such a catastrophe with the additional penalty that health insurance—once they can afford it again—be unavailable or unaffordable.

My wife and I have modest incomes, and make some use of the credits available through the Affordable Care Act, which have made my insurance much more affordable. Speaker Ryan’s plan would eliminate these credits and replace them with a single credit which would probably be much smaller—and if as large, would be enormously generous to people with high incomes who scarcely need help affording their health insurance. The current means-tested credits seem much more likely to advance to goal of making health insurance available to everyone.

I urge you preserve these key elements of the Affordable Care Act.

Yours sincerely,

Philip M. Brewer

There are plenty of other things I might have included as well. For example, under the Affordable Care Act an older person can only be charged 3 times as much as a younger person for the same policy, whereas the Speaker’s plan would increase the multiple to 5x. If enacted, that change would cost me a lot. But I thought these were the most essential points: That insurance actually be insurance, that it be available, and that it be affordable.

Theory and Practice of Neurogenesis

Even though I’m finding my self-care regimen for seasonal depression pretty adequate these days, I’m always interested in more tools. One thing that caught my attention recently was an interview with Brant Cortright in which he talked about his book The Neurogenesis Diet and Lifestyle.

Cortright has a bunch of interesting things to say, one of which I already knew: that depression is not a disorder of serotonin deficiency. According to him—and this I did not know—the way SSRIs work is by promoting neurogenesis. In the interview he said that depression turns out to be caused by a lack of neurogenesis, as are several other disorders (e.g. Alzheimer’s).

I checked the local libraries for copies of his book without success, but in my searches I happened upon this article: Successful brain aging: plasticity, environmental enrichment, and lifestyle by Francisco Mora, which seems to cover pretty much the same ground.

People are looking very hard at drugs besides SSRIs to promote brain plasticity, but the whole idea sounds problematic to me, so I’m interested in the various non-drug interventions suggested by Cortright and Mora. Fortunately, it seems that neurogenesis is easy to increase, by doing the obvious things we already know about:

  • Environmental enrichment
  • Calorie restriction
  • Aerobic exercise
  • Adequate levels of certain nutrients (omega-3s, vitamin E).

I think of my artist dates in particular as environmental enrichment, but of course time spent in nature counts as well. The parkour I do probably counts double, because there’s learning how to execute the moves, but there’s also learning to see the environment as a place where those moves are useful.

My weight loss practices have been substantially motivated by the science around calorie restriction as a way to improve health generally, with additional neurogenesis just one factor.

My experience over the previous 30 years convinced me that approaching calorie restriction in a numerical, analytical fashion—tracking what I ate, estimating the calorie content, aiming for some target X% below maintenance—would be unsuccessful. Instead, I came at it from the other direction: If I’m losing weight, I must be restricting my calories.

The caloric deficit implied by my weight loss over the past five years is just about 100 calories per day. Maintenance for me is probably around 1800 calories per day, so I’ve averaged about 5.5% below. It would probably be more accurate to say that I’ve averaged about 10% below maintenance for about half that time, as I’ve generally lost weight during the summers while maintaining a stable weight through the winters. Either number is well shy of the “20% to 40%” reduction that’s been shown to decrease the rate of aging of the brain, but I rather suspect that the benefit exists even at these lower levels—with the added bonus of being sustainable over a much longer period of time. (I mean, how long can you maintain a 40% deficit below maintenance before you simply waste away?)

According to Mora, aerobic exercise seems to increase neurogenesis by the same chemical pathways as calorie restriction. According to Cortright, it has to be aerobic activity of substantial duration—some twenty minutes or more. In particular, the sort of HIIT workouts so beloved of the paleo/primal folks don’t seem to produce the same effect. That’s fine with me: Humans are much too well-adapted for endurance running for me to buy into the idea that primitive humans didn’t do marathon-distance runs when they needed to. Besides, I enjoy long runs.

Of course, neurogenesis is reduced by the obvious things:

  • Neurotoxins (mercury, lead, pesticides, etc.)
  • Traumatic brain injuries (concussions, etc.)
  • High blood glucose levels
  • Stress.

My parents made a considerable effort to keep me and my brother free of neurotoxins, and I have managed to avoid concussions so far. I’m sure I subjected myself to excessive blood glucose levels for years, but I think I’ve got that under control now. I also subjected myself to excessive levels of stress for years, due to the vicious circle of my seasonal depression making me unproductive, my lack of productivity making me stress about losing my job, and the stress no doubt worsening my depression. I’ve got that under control now as well.

Really then, this whole neurogenesis thing doesn’t so much give me new strategies for staving off depression, as provide a conceptual framework for organizing the strategies I’m already using.

Even just that seems worthwhile.

(The image at the top is of these great doors at the Environmental Education Center at Kennekuk County Park. The branching trees reminded me of neurons, a little.)