Can We Reach Extreme Longevity with a “Natural” Approach?

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by Nils Osmar. May 15, 2022

Imagine that you had the power to bring together several thousand people who were interested in longevity. If you asked them about their approaches, you’d find a lot of variations. In terms of diets, you might find:

  • vegans
  • vegetarians
  • omnivores
  • carnivores
  • pescatarians
  • people eating the CRON diet
  • people eating paleo/ancestral diets
  • and more

Broadly speaking, though, they would break down into just two groups:

In Group One…

… we’d find people interested in living to be 90 or 100, or maybe even 105, in good health, before they die. Their motto might be that people should “age gracefully”. Their goal might be to feel good physically as their aging — to stay healthy, have good energy, and be able to think clearly as long as they’re around.

They might tell you that when when they get too old to enjoy life anymore, at that point, a nice ending might be to pass on quietly in the company of their loved ones. 

Their path forward would be to go natural as much as possible. An ideal image of this, from their POV, would be drinking pure stream water; breathing clean mountain air; and growing their own natural, organic food in their own back yards. Or coming as close to this ideal as possible.

In Group Two…

… we’d find those who are interested in the possibility of physical immortality: ie., doing away with the aging process altogether.

Aging could be regarded as a disease, from their point of view; one that we all unfortunately have. Why not do away with it as a cause of death, just as we’ve done away with, or minimized, some other diseases that used to kill people in large numbers?

Their motto might be, “Why bother aging in the first place?” Or even — “Why die?”

People in this group might tell you that while eating organic, breathing clean air and drinking pure water are all fine, they won’t get us to immortality. From their perspective, something more basic is needed, which would be likely to come from advances in medical technology.

If Pfizer or some other company ever developed an effective vaccine against aging, they’d be first in line to take it.

A Bit of Both?

In reality, I don’t think we can separate the so-called natural approach from the technological.

We can’t all drink pure stream water, but we can get close to the same benefits by using a good water purifier or distiller, which of course is based in technology.

We  can’t all live in the mountains, but we can use air filters and purifiers to remove dirt and dust and noxious gases from our indoor air.

Filtered water and purified air are technological solutions on the path to what many people think of as a more natural way of life.

It Depends On Your Goal

Where the groups differ would be mainly in their longer range hopes or goals. Those in Group Two would have no objection to living to 90, 100, or 105 (as a start). But they’d see those as steps toward a more important long-range goal.

Their question –- and mine –– would be, why stop there? If it turns out that we have the capability, why not live to be 150? Or 200? Or 300 or more?

Aiming for Immortality

Group One might answer, “Oh, get real. If we really could live to be 150 or 200, we’d be so old and frail by the time we got there, we wouldn’t want to live anymore.” 

But what if we didn’t need to get old and frail? What if we could freeze the aging processes at a certain age, or slow it glacially –– or even reverse aging? What if we could be as healthy at the age of 100, or 200, or 300 as we are at 20?

Why “age gracefully” if we may not have to age at all?

If we get cancer, most of us don’t set a goal of coexisting peacefully with it. We don’t talk gently about hoping that we all have pleasant strokes or heart attacks. We don’t tell people they should “die of cancer gracefully”. I suspect that the reason we’re so adamant about the idea of aging may be that we’ve given up on the possibility that we may be able to not age at all.

Is Death Inevitable?

Most of us learned about growing older and dying when we were young. We may have had a pet that died, or a friend or relative.

We asked our parents about it, and were told that everyone and everything dies–– that we may not like aging and dying, but there’s nothing we can do about it, so we should just forget about it, or even try to find the divine inner wisdom of cooperating with the inevitable. 

But what we’re looking at in the longevity movement is the possibility of a paradigm shift ––– that maybe, someday, everyone who wants to will have the option of staying young and healthy as long as they want.

We could still die of other things, of course; if a car hits you or your plane crashes, you could still get badly injured or killed. But if we learn how to prevent aging, we would not grow old or die from old age anymore. 

And we’d be less likely to die from cancer, heart disease or diabetes, because those are all exacerbated by aging.

Some would say that it’s ridiculous to ask whether we might live forever. (It’s unthinkable to them because it’s never been done before.) Interestingly, many of the people who say that are the ones who’ve embraced religions that promise that they’ll live forever on another plane of existence. They’re still interested in immortality, they’re just moving it to another location in their beliefs.

Steps in that Direction

Is the end of aging possible? Or is this all just speculation? The truth is that no one knows, really.

There are signs that aging could be done away with, or at least slowed down. The research is in its infancy. Still it does show some promise.

At the time that I’m recording this, we have interventions that could very likely help us to live 20, 30, or even 40 years longer than the usual lifespan. Animals fed calorie restricted diets or periodically fasted, for example, live up to 50 percent longer than those that are free to eat unlimited quantities of food whenever they want. Certain nutrients and pharmaceuticals are also associated with an increase in longevity.

Longevity Pathway(s)

The research has established that an enzymatic process called AMPK is the longevity pathway. AMPK is associated with autophagy, apoptosis and activation of the PGC1-alpha gene. If it’s activated in lab animals, they live much longer.

They stay healthy well beyond their expected end of life –– and have good eyesight, good energy, and stay mentally sharp and clear. Some mice on the longevity pathway live for three or four years in a laboratory setting, instead of two years like their littermates.

The Growth Pathway

We also know that a different enzymatic process called mTOR is a growth pathway. This pathway can help us to build strong muscles, but if it’s “on” all the time, we’re very likely to die young. If it’s switched off periodically, or kept on a slow burn most of the time, lab animals live much longer.

Some mTOR activity is needed to prevent dementia, keep our immune system effective, and keep our muscles strong as we age. But activating it constantly by incessant nibbling; or eating foods high in leucine at every meal is associated in lab animals with a shorter than usual healthspan.

We know that some drugs, including rapamycin, can switch on AMPK and lower mTOR in mammals. MTOR in fact stands for “mammalian target of rapaymycin.” 

Rapamycin really is a key anti-aging drug, and it’s reasonable to expect that taking it could result in longer lifespans. It has some side effects, but the idea would be to take it and handle those side effects as they come up.

Can We Live Longer Without Drugs?

Can we get to the same place without drugs? To a degree, yes, because what we eat and drink can have a drug-like action.

Eating a diet that’s adequate-but-low in protein, or one that’s high in protein but low in methionine, are ways of lowering our mTOR and switching on AMPK (doing with food what some people do by taking rapamycin). Fasting can turn on AMPK and switch mTOR off too.

When I look at the possibility of “eating for longevity”, I can see paths that might lead in that direction, and paths that might leads to dead ends.

Leucine, Glycine and Methionine

I was vegan for a few years, so in theory should have been activating AMPK much of the time. But for a number of reasons, eating 100 percent plant-based did not work out for me. I actually gained about 50 pounds of excess body fat eating a vegan diet, lost muscle, and ended up feeling sick much of the time.

I began adding back in eggs, then fermented dairy,  then fish, poultry, and later red meat back into my diet. I got lean again, gained some muscle, and the health problems I’d been experiencing when I was vegan all went away.

Some time later, largely out of curiosity, I went carnivore for a stretch of time, eating only animal-based foods. I had lots of energy and great mental clarity during this stretch. But as I learned more about anti-aging, and the problems associated with constant mTOR activation, I realized that I was on a path toward “health without longevity,” so I stopped following a carnivore diet.

So What to Eat?

We do have to eat something; the question is how to retain the right balance. To put it mildly – opinions vary. Most researchers and doctors who claim to that their approaches are anti-aging recommend keeping protein low to keep mTOR mostly “off” and AMPK activation high. But they have very different ideas of what “low protein” means.

  • Dr. David Sinclair has recommended following a diet which is plant-based but includes some animal foods. (He doesn’t currently eat meat, but he does eat some fish, poultry and cheese.) His template is low in protein (to control mTOR); low in carbs (to control insulin and mTOR), and high in healthy fats such as avocados and olives, sources of oleic acid. He advocates sipping breakfast and lunch, being hungry most of the day, then having a bountiful mostly plant-based dinner. Sinclair is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School.
  • Dr. Valter Longo recommends what he calls “a vegan diet plus some fish and other seafood” — a pescatarian approach. It’s a bit higher in carbs than Sinclair’s diet, but is also low in protein and high in fat. Longo is the Edna M. Jones Professor of Gerontology and Biological Sciences and Director of the Longevity Institute at the University of Southern California.
  • Dr. Dom D’Agostino believes that We should probably all be eating Modified Atkins Diets.” (Modified Atkins is a very high protein/animal food based diet which also includes some low glycemic plants such as salads). Everyone should work out. Weight training is essential. Like Sinclair and Longo, Agostino believes in keeping protein “low or moderate” — but his sense of what’s low is very different from theirs. According to D’Agostino, “We need at least 1 gram of protein per pound of body weight. Ketogenic diets have profound health benefits, and may be of key importance to life extension.
  • Dr. Rhonda Patrick: Believes that we should eat the highest nutrient foods available, a balance of animal and plant foods, and not restrict protein. She views both vegan and carnivore diets as possibly being helpful for a short time, but not the best choice long-range. She’s a big fan of fasting. Patrick does not currently take or recommend metformin, NMN, NR. She does take resveratrol. She has noted that we need more protein as we age or if we exercise more. Has stated that activating mTOR shortly after resistance training is not pro-aging. Eats a high-nutrient diet rich in kale, greens, salads, fish, chicken and eggs. Has said that she eats red meat “several times a month”.
  • James Clement: We should alternate between activating mTOR and activating AMPK. (Note: this book was highly recommended by Dr. David Sinclair, in spite of his differences with Sinclair.) It’s dangerous to activate AMPK all of the time. (Clement has spoken recently about people whose health took a disastrous turn for the worse when they went vegan in an attempt to activate AMPK full time) (He has said that many of them now look much older than their biological age but could reverse that by eating meat and activating mTOR).
  • Dr. Paul Saladino, M.D. Saladino is an outlier with contrarian views. He has been a vegan in the past, then a carnivore. He’s currently a carnivore/fruitarian. After advocating eating “only” meat for a few years, he added in honey, then fruit. He believes that we should eat an equal amount of meat and fruit, plus honey, but avoid all plants (never eat the plant itself, i.e., the roots or leaves), because plants, which animals have eaten for hundreds of millions of year, are trying to kill animals. The best longevity diet is a fruitarian/carnivore diet extremely high in protein.
  • Dr. Michael Greger: Dr Greger is an advocate of a salt-, oil-, and sugar-free whole food plant based diet. He believes that we can and should get all the nutrition we need from plants. Greger is of the opinion that people eating diet with no animal foods in it will live longer. The best longevity diet (in his opinion) is 100 percent plant-based… no food at all from animal sources … a 100% vegan diet.
  • Dr. Peter Attia: Attia believes that while vegan diets can be made to work with great effort, animal-based diets are have a higher nutrient profile and should be included in our diets. He believes we need about 1 gram of protein per pound of body weight to maintain muscle as we age. He thinks immortality or even living much past 120 is probably impossible. He takes rapamycin but won’t prescribe it for his patients. He’s stopped taking metformin and views NR, NMN and resveratrol as probably being of little value. Used to do a three day water fast once a month; now has cut back and believes that much fasting may be dangerous.
  • Dr. Gabrielle Lyon: She maintains that muscle is the organ of longevity. mTOR activation is essential. We all need at least one gram of protein per pound of body weight, minimum to avoid Alzheimer’s and other types of dementia. Believes animal based foods are superior to plant-based foods, but a vegan diet can be made to work with effort. Lyon writes of seeing dozens of her elderly patients succumb to dementia when their protein was low; she was able to turn it around in some patients by getting them to eat animal-based protein, one gram per pound.

What I’m Eating

My diet these days is based around optimizing my nutritional intake while alternating between the activation of mTOR an AMPK. I try to keep AMPK activated most of the time, but when it’s time to activate mTOR, I’m not shy about it.

Plant-Based Foods

The phrase “plant=based diet” is tossed around a lot these days, but any two people could use it and mean very different things. My diet is largely plant-based by volume; but it also contains some foods from the plant and fungus kingdoms.

For example, I eat lots of green salads (romaine and aragula), as well as lentils, onions, garlic, green peas, broccoli, kale, beet greens, parsley and celery. I eat some fermented vegetables such as kimchi, and lots of cruciferous and leafy vegetables. Plant-based foods tend not to raise mTOR because as a group they’re low in both protein and leucine (an amino acid that signals to our body that “times are good”).

Fungus-Based Foods

I eat several different fungus-based foods every week, i.e., a variety of different mushroom, some raw, some cooked. Mushrooms are not plants, but are actually biologically closely related to insects. They’re rich in spermidine and other polyamines, associated with a slower aging process and with life extension.

Plant-based foods and fungus based foods both tend to activate AMPK rather than mTOR.

Animal-Based Foods

I also eat foods from the animal kingdom, from both land and sea. They include staples like mackerel and sardines, wild Pacific sockeye salmon, salmon roe, some red meat, and some organ meats –– all of which tend to activate mTOR.

The fish that I eat is low in mercury; the plants foods are organic; the meat is from small family farms where the animals are treated well and allowed to graze on grasslands, not pumped full of antibiotics and hormones or fed grains sprayed with Roundup.

I add the amino acid glycine (or collagen or gelatin, which are naturally high in glycine) to the meals that are high in methionine because of research showing that doing so has almost as much benefit as omitting methionine entirely. The glycine counters the bad effects from methionine, and give us the option of eating protein rich foods. Though again, we still don’t want to overdo protein if your aim is longevity.

Many of the foods that I’ve listed are high in methionine, which does activate mTOR. So I don’t eat them all the time, even when I’m adding glycine to them.  And I have days off when I’m either eating nothing, or eating foods with no protein such as avocados. I’m currently cycling between mTOR activation and AMPK activation, with AMPK activated about 90 percent of the time. 

How Much Protein?

I’ve changed my protocol a few times. I’m currently aiming to eat one gram of protein per pound of body weight on my workout days, but to eat lower protein, more plant-based diets on my non-workout days. I work out three times a week.

My current protocol is to get up in the morning, have some coffee, then have a fasting-mimicking-smoothie, which keeps AMPK activated.

After that, if it’s a workout day, I work out in my home gym for an hour or so, then have a high protein, mostly-animal-based breakfast such as scrambled eggs with mushrooms, broccoli and sardines, or Greek yogurt with whey powder, and blueberries or liver and onions with broccoli and mushrooms.

This “feast or famine” approach –– interspersing meals rich in protein with stretches during which we’re either fasting or eating lower protein, lower leucine plant-based foods –– seems to me to closely mirror what our early ancestors lived through. So in that sense, it’s a natural approach.  My “ancestral diet” includes lots of ancestral fasting, so my mTOR won’t be activated full time.

Will my eating this way stop the aging process in its tracks and make me live forever? I would love for this to be true, but I don’t think it is.

Would my taking rapamycin stop the aging process in its tracks and make me live forever? Again, I don’t think so. But it does seem possible that eating this way, along with keeping NAD levels high, keeping blood glucose low, switch on autophagy and apoptosis periodically, while keeping AMPK activated most of the time, might, possibly, help us reach the point of escape velocity ––– the point at which medical technology has advanced enough that every year of life brings scientific breakthroughs that can bring us more than a year of life.

At that point, we’d be looking at a 100 percent medical, 100 percent pharmaceutical approach. It could well involve genetic reprogramming. It would pretty much have to, I think.

We can still eat organic and try to drink pure water… in my opinion, it would be good to.  But we’d looking at medical, pharmaceutical interventions… ones that may be on the horizon… to take us over that last hurdle.

The point of “going natural”, to me, is to live live long enough that an approach that goes way beyond what can achieved by eating right and taking the right supplements, is available. I’d count taking supplements like berberine or medications such as metformin and rapamycin, as natural approaches. Berberine and metformin come from plant compounds; rapamycin comes from a natural compound which was discovered years ago in the soil. 

There’s no guarantee that escape velocity will ever be reached. It seems likely to me, but not inevitable. But it’s a fun thought, so my feeling about it is, why not try?

Do we have drugs yet which will completely stop the aging process? No, but researchers are working on them. Rapamycin shows that drug-induced alterations to the aging process are possible. I suspect that as time goes on, we will have much more powerful anti-aging drugs building on the same biochemical architecture in the next thirty or forty years.

At that point, aging will have to be recognized by doctors as a disease condition. (We may actually have the cure before the diagnosis.) Doctors will routinely start patients on very powerful anti-aging drugs somewhere in their forties or fifties. The drugs will probably slow aging at first. It’ll become typical for people to live to be about 120, 130 or 150 years old.

Then more drugs will come along which clean up the damage that even a slowed-down aging process can cause. At that point, we might be on the path to no longer dying from old age, because the aging process will have been effectively done away with as a cause of death.

What Kind of Future?

Will this lead to problems such as even more pollution, inequality and overpopulation? It could, but there’s no reason it should have to. Curing heart disease and cancer could lead to overpopulation too, but we’re not arguing against curing them for that reason.  If problems of that sort do occur, we’ll have quite a stretch of time to solve them.

In many countries, the population is actually dropping these days due to a decline in fertility; living longer may end up just balancing out that decline.

Will any of this really happen? I would say, maybe. We don’t know what the future will be.

To me, planning for a future like that would also involve things like cleaning up the environment, making sure people all over the world have clean air, clean water, food that’s high in nutrients, and access to medical care when they need it.

It’ll also involve shifting medicine over to an approach that recognizes that preventing aging is the most effective and cost-efficient way of preventing cancer, heart disease and diabetes.

Including Everyone

It’ll be important, in my opinion, to make sure that life extension isn’t only available to people in relatively privileged groups, any more than other medical interventions should be. You don’t have to agree with this, but I did want to express it here. Just like other forms of medicine, life extending technologies should be available to everyone who wants access to them.

One thing I like about David Sinclair’s approach is that he doesn’t view dramatic increases in life expectancy as being only for the wealthy, but as something that, if it does turn out to be possible, could change everyone’s lives for the better, not just the lives of the very rich. We could have time to do everything, instead of just some of the things we want to, to find solutions to the other problems facing the world, and to really figure out our lives.

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