Friday, September 15, 2017

Longevity: Superhumans vs. CRONies

There are, broadly speaking, two very different paradigms, or approaches, to longevity.  Or, you could say, approaches to longevity can be split into one of two different general camps. I'm going to roughly lay out both of them, but please remember, both camps represent a set of philosophies - not every researcher or doctor or longevity enthusiast who supports either side is saying exactly the same thing; there's variation within each group both on exactly what people are supposed to be doing and the reasoning or explanations about why they should be doing it.

CRON: Caloric Restriction, Optimal Nutrition

The first, in the sense of being more popular and better known in the popular media, is CRON, or Caloric Restriction/Optimal Nutrition. People who follow CRON are sometimes called CRONies,

The CRON paradigm is, at its most basic, that humans can achieve greater longevity by restricting caloric intake below what is considered maintenance levels. The CRON approach is almost always constant - that is, CRONies will find their basic caloric needs, then restrict themselves to some number of calories between 15% and 40% LESS than that number, forever. They believe that doing so will increase their maximum lifespan, and presumably their average lifespan (in other words, CRONies tend to think that consuming so few calories, forever, will help them live longer, at least longer than the average person and possibly longer than even very long lived 'normal' people).

In the earlier days CRON was really CR - focusing on Caloric Restriction - but nowadays most proponents of this lifestyle are careful to emphasize optimizing nutrition. After all, if you eat many fewer calories than you need each day, that means you have to eat less food overall, so you have to be extra careful that the food you DO eat has a high nutritional value, so you don't introduce nutritional deficiencies that might increase chance of disease or degeneration, counteracting the benefits of plain CR.

Reasons to think that CRON does, in fact, work:

The CRON plan is based on some very solid science. In a large variety of lab animals, like worms and mice, controlled studies have shown that chronic CR (caloric restriction that lasts the animal's entire adult life) extends average and maximum lifespan. I don't mean to shortchange the importance of this evidence by making this list so few words - it's exceedingly relevant that in many living things, CRON (or, more specifically, CR) increases lifespan.

The general idea is that CRON extends lifespan using one or more mechanisms that can be loosely grouped like this:

  1. Prevent the damage that seems to cause aging by slowing the metabolism and slowing activity, which should slow the production, for example, of reactive oxygen species or free radicals.
  2. Prevent or slow the processes that might contribute to cancer formation by reducing the signalling that activates them (for example, high protein activates mTor pathway, which might increase cancer growth; to prevent that, eat relatively little protein). In other words, prevent growth and growth promoting mechanisms.
  3. Engage the body's catabolic 'cleanup' mechanisms (like autophagy) that remove old cells and damaged proteins by mimicking a famine state.

Reasons to Doubt that CRON works:

  • CRON isn't really proven in humans, or even well studied in primates, because longevity studies in long lived animals is really, really time consuming. Just think - it would take 100 years to do a really good CRON study, and that means you'd have to find a test population willing to half starve themselves for 100 years. This same criticism goes for every other longevity program, of course.
  • CR is hard to do. It's physically very demanding (try staying on a strict diet for the rest of your life - if it were easy, we wouldn't have an obesity epidemic in the first world). You get cold, irritable, thin, listless, and so forth. A common joke about CRON is that it may not work, but it certainly seems to, because the suffering makes it feel like you're living longer. So the chances of finding people who can stick to CRON in the numbers you'd need for a valid study are really small.
  • Nobody knows exactly why CRON works in smaller animals. One popular study stated 400 hypotheses about why CRON works. The truth is that the key to CRON's success might be in any one or any combination of those 400 hypotheses. Maybe it's reduced oxidative stress from reduced basal metabolic rate. Or increase in autophagy. Or an increase in protein recycling caused by chronically limited protein intake. Or a huge slowdown in mTOR activation. The fact that we don't know why CRON works in animals makes it very hard to study why it might or might not work in humans - if we knew it was mTOR deactivation, we might measure that in a shorter term study. But we don't.
  • CRON seems quite antithetical to many quality of life markers that people who want to age well are concerned about. A big reason many aged people have poor quality of life is related to sarcopenia (reduced muscle mass). Chronically restricting calories is not a good way to preserve, let alone increase, muscle mass as one ages, in two ways. First, reducing calories encourages the body to burn muscle tissue directly. Second, reducing calories reduces activity levels, and it is activity which causes the body to retain and increase muscle mass. Living longer, but being either too weak to get out of a chair or at least finding it hard to do so, might not be a very high quality of life.
Basically, CRON is all about reducing calories, increasing catabolism (breakdown of tissues), reducing metabolic rate, slowing biological processes that might contribute to aging, all in an attempt to increase the deleterious effects of time on the body. It's not eas

Is there another option?

The Superhuman Paradigm

I take the name of this paradigm from Carl Lenore, host of a radio program called Superhuman Radio. Carl is the person from whom I took the core ideas of what I'm calling the Superhuman Longevity Paradigm, but I'm not saying he's the first or only person to propose them, only that he's my personal source for the idea. Also, I find Carl's politics abhorrent, to the point where I think if we met we'd end up punching each other, so please don't think that I'm in Carl's corner generally. But I find his stance on longevity very interesting, and very different from CRON.

Roughly speaking, the Superhuman Paradigm is sort of opposite to the CRON paradigm.

The Superhuman Paradigm is focused on quality of life, not quantity. It's less about avoiding death by old age and more about avoiding the deleterious effects of aging. It's about increasing physical capacity and restoring youthful abilities more than about slowing the deterioration of those abilities.

In the Superhuman Paradigm, it's great to live a long time, but the real goal is putting off for as long as possible the point where you are infirm, in a wheelchair, stuck in a nursing home. The Superhuman Paradigm isn't opposed to a long lifespan, but it's more interested in being physically vigorous and able for as long as possible. I should say that people invested in this paradigm usually believe that this lifestyle will ALSO increase lifespan, but that isn't the sole driving factor.

How does the Superhuman Paradigm work?

The Superhuman Paradigm is focused on building those physical qualities that usually deteriorate with aging. For examples: strength, muscle mass, bone density, power output, maximum heart rate, sex hormone levels, and glucose tolerance. How are those qualities increased? With increasing emphasis on the activities that we already know will improve those things. In other words, do the same things (roughly) that powerlifters or bodybuilders or Olympic weightlifters (or even crossfit athletes) do, but continue to do them as much as possible as aging continues (unlike traditional athletes, who transitioned from those activities to gentler training as they aged).

The Superhuman practitioners focus on lifting relatively heavy weights, often explosively. They eat a surplus of nutrients, especially protein, though careful not to increase bodyfat levels too much. They might engage in supplemental nutrition or medical interventions, like hormone replacement therapy, but the goal is to get closer to a young person's profile.

While the CRONie is eating 1500 kCal/day, the Superhuman is doubling that, spread across 6 meals, and banging out an hour of walking in the morning and a heavy deadlift session in the afternoon. While the CRONie is trying to minimize activity (with no choice, because you can't work out heavy in a high caloric deficit), the Superhuman is struggling to reach personal records in the heavy lifts.

Reasons to think Superhuman Plan does work:

There is indirect evidence to suggest that the Superhuman lifestyle will increase health and lifespan (but also indirect evidence that it won't). We know weight training increases bone density. We know that increased bone density is preventative for major breaks (like fractured hips). And we know that breaking a hip does bad things for your lifespan. But there isn't a lot of (or any) real data on the health or expected lifespans of 60 year olds who can deadlift 450 lbs.

Reasons to think the Superhuman Plan won't work:

Heavy weight training might not be sustainable for many decades, because of the wear and tear on the joints. There are certainly many people who have lifted heavy well into advanced age, but not entire populations of such people, so those who have done so might be genetic anomalies.

Of greater concern, the Superhuman plan is highly pro-anabolic - that is, you're doing many of the things that increase anabolic signalling in the body (like activating mTor and increasing IGF-1) both through diet (high protein and moderate to high carbohydrate), hormones (activities that increase anabolic hormones, and possible hormone supplementation), and exercise. And there is some indication that increasing anabolism might increase the rate of cancer formation or cancer growth or both. 

It is also unclear what the relationship is between some pro-anabolic signals and endothelial health. We know that people who abuse anabolic steroids (rasing androgenic levels in the body to superphysiological levels) increase their risk factors for some kinds of heart disease. Does that mean that stimulating anabolic hormones for decades, but keeping them in ranges that are normal for younger people, could have a similar effect? We aren't sure.

But Joe, what should I do? Which Paradigm is better?

It's probably obvious, but my heart lies with the Superhumans, not the CRONies. Living longer as a lethargic, weak, fragile person is not my idea of a goal worth pursuing. I am much more afraid of life as an invalid in a nursing home than I am of death.

However, and this is a fairly big 'however,' cancer is not fun, and dying young but leaving a jacked, muscular corpse is not my idea of a goal worth pursuing either.

Ideally, we could find some way to combine the benefits of both approaches. But this isn't a simple case of following both protocols - it's not as if one group was saying, "get enough sleep!" and the other group was saying, "take resveratrol supplements!" Then you could conceivably do both. But you can't reduce calories to 25% below maintenance and still lift heavy - it's just not physically possible.

A Shining Hope: The Sidekick Longevity Plan (intermittent fasting, maybe?)

The best hope we have for some lifestyle that could combine the benefits of CRON with Superhuman living is some kind of intermittent or periodic fasting.

What's the idea here?

Ideally, you could spend periods of time eating in a caloric surplus. You'd have loads of energy, and extra fuel in your system to support building lean muscle tissue and increasing bone density. You'd be strong, dense, and have a high physical capacity.

Then you'd spend periods of time eating less or no food at all. You'd be temporarily depleted, which should kick in the body's repair mechanisms, the same mechanisms that get rid of damaged proteins and cells, that clears small cancers from the body, that restore insulin sensitivity, and so on.

Yes, you'd probably lose some muscle while fasting, and promote some undesirable growth while feasting, but if you could get the proportions right, you could build or maintain muscle while still minimizing the risks of cancer growth. Or, get them wrong, and promote cancer while losing lean body mass.

Is this remotely feasible?

There is actually plenty of evidence that short term fasts promote mechanisms that prevent muscle loss - in other words, a short fast probably doesn't carve up as much muscle as people think (a fast often seems to really destroy muscle, because even a short fast will deplete glycogen levels, making your muscles look significantly smaller, but it's not real muscle tissue that's been burned off - once you take in surplus carbs again those glycogen stores are replaced within hours).

So how does this work?

A fast can mean:
  • No food at all (but plain water is fine, and maybe water with some flavoring - nobody really favors limiting fluid intake altogether); or
  • Significantly reduced food intake (think 60-80% below maintenance); or
  • Normal energy intake but highly reduced protein and/or carbohydrate intake (reduce protein to reduce mTor activation and induce autophagy; reduce carbs to reverse problems related to insulin overproduction).
Done for:
  • 14-20 hours daily most days (so you fast from the end of, say, dinner on one day through the beginning of lunch the next) - this is usually 'no food at all'; or
  • 24-36 hours at a time, once or twice per week - this is usually 'no food at all' or significantly reduced food; or
  • A 3-5 day fast repeated at most once per month, either full fast (be careful!) or reduced protein or ketogenic; or
  • Periods of time spent in ketosis each year - ketogenic diets are high in fat, low to moderate in protein, and very, very low in carbs. You can follow this diet indefinitely, but there are good reasons to think that spending a couple of weeks or a month every year or so might have some benefits, while staying in ketosis long term might have drawbacks.
There are some other protocols, but you get the idea.

What's the best one?

Sadly, I don't really know. My strongest hunch is that mixing things up is best. Try to do 16-20 hour fasts a few days a week, a 24 hour fast every 2 weeks, and go very low protein for a week once a year. The damage you'll do with a strategy like that is pretty minimal (as long as you don't use these fasts as an excuse to overeat when they're over).

Hopefully, as time goes on we'll get more research showing specifically how different fasting methodologies can impact different health markers more specifically.

Now; why do I call this the Sidekick Plan? Answer: because I can't turn down a chance to make a bad pun. Crony + superhero = sidekick. I am sorry.

Implementing the Sidekick Longevity Plan:

A few caveats:
  • If you're under a lot of stress (if your sympathetic nervous system is highly activated) then fasting is going to potentially be such a big stressor that it's going to negatively impact your health. How can you tell? Well, if after starting some trial fasts you feel anxious or jittery or find that you're not getting good quality sleep, you might want to ease back on the fasting.
  • The idea that the Sidekick Longevity Plan will actually improve your lifespan or your health is not well supported by science. It's a good guess, based on lots of disparate pieces of data. The fact is, there is almost no good direct science on this, or almost any other, plan for increasing longevity. We're all just guessing (but they're educated guesses).
  • Monitor your lean body mass and overall body mass carefully. If you're losing muscle, then you're fasting too often or eating too little during non-fasting periods. The goal here is to maintain a lot of excess muscle so that as you age, any incidents that occur (accidents, illness, etc.) don't deteriorate your body to the point that you're incapacitated. The goal is to be able to get really sick, lose 30 lb. in the hospital, and still come out able to deadlift one and a half times your bodyweight.
  • If you're sick, acutely or chronically, start fasting only under a physician's care. Especially if you have some kind of metabolic illness.
  • Pregnant or nursing? Don't fast. It's possible that pregnant or nursing moms can fast safely under certain situations, but we aren't sure, and to be honest that research is NEVER going to get done. And the cost benefit ratio here is terrible. 
Now, if you've decided to try fasting, there are plenty of resources around (google intermittent fasting). There are many different plans - I've tried lots of them.

I recommend starting with a 16 or 20 hour fast. Have a solid dinner, finishing, let's say, at 8PM. Eat no food before bed. Skip breakfast the next day. Eat lunch around noon. Congratulations - that's a 16 hour fast. If you can eat a late lunch or skip lunch altogether, you can push that to 20 hours.

Keep an eye out for jittery feelings and poor sleep. If you're overstressing yourself you're probably not doing your body any good.

Plan your fasts to avoid being around your heavy workouts. For example, if you hit the weights hard on Tuesday and Friday morning, you should eat normally Monday and Wednesday dinner and Tuesday and Friday all day. If you want do do a 36 hour fast, do it Sunday, so you have Saturday to recover from Friday's workout and Monday to reload for Tuesday's. If you do a are doing some 20 hour fasts, do them Wednesday and Sunday. So don't hit the weights hard Tuesday morning, then come home and NOT eat. Your goal is to get whatever calories your do eat into muscle tissue - which means focusing your food intake into time periods just before and for a while after your workout.

Lastly, keep your eyes out on the research. shorter fasts (16-20 hours) seem useful for increasing insulin resistance and weight loss. Longer fasts, either total fasts or simply low-protein fasts, seem to be needed to get the cancer fighting benefits. But all of this is very speculative, at least for now.

On ANY calorie reduced plan - CRON or Sidekick - you should probably be extra careful to eat nutrient dense food. That is, focus on foods that have a lot of micronutrients (vitamins, minerals, phytochemicals) and the critical macronutrients (Omega 3s like DHA and EPA, high quality animal protein, monounsaturated fats, fiber). That's the 'ON' in CRON. When you're in a large caloric surplus, you're just eating a lot of food, even if the food is slightly lower in quality you're still likely to get the nutrients you want. The less you eat, the more particular you have to be about what you're eating.

NEVER RESTRICT WATER. "Drying out" can make you look leaner, but there are NO positive health effects to dehydration (that I'm aware of) and NO evidence that dehydration could complement any of the beneficial mechanisms of fasting. Fasting is very safe - unless you're a Type I diabetic taking exogenous insulin, skipping a few meals or a few days of meals will NOT kill you - but dehydration is NOT SAFE.

For the Martial Artists:

Obviously, CRON is a bad choice if you care at all about physical or athletic performance. Sustained caloric deficits do NOT work with hard training. 

But the Sidekick Lifestyle can work with martial arts. Plan your fasts to be on rest days, make sure you aren't losing muscle mass, and train during times when you're getting in plenty of fuel.

For the CRONies, Superhumans, and Sidekicks alike: EVERYONE DO THIS

The basic tenets of CRON and Superhuman and Sidekick lifestyles are at odds, but there are many factors that seem to contribute to extending lifespan that we should probably all be doing. For examples, in no particular order, of lifestyle tips that seem to coincide with long lifespan and with health:
  • Get enough sleep, primarily at night.
  • Get adequate sunlight exposure.
  • Do lots of socializing.
  • Reduce stress (yoga, meditation, whatever).


Nobody has great direct evidence supporting any particular plan for living a very, very long time. There are two approaches that represent a best guess, based on what works to increase longevity in animals and based on ways to improve health indicators that are indirectly related to lifespan. One is to restrict calories dramatically. The other is to increase calories, combined with heavy, tissue building exercise. A third approach that might provide benefits of each of these other plans is to alternate periods of caloric surplus and heavy training with periods of caloric deficit. I call this the Sidekick Plan, because I can't resist bad puns.

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