Science Thinks Out of the Box to Extend Lifespan…
Long life is a perennial yet elusive goal. Ancient writings, including the Bible, abound with stories of people living far beyond today’s lifespans. Longevity was considered an award for virtue, or an endorsement by God (or, by the gods).
We don’t want just any long life, of course. We want a long life in top health, with full mental faculties and without pain. This is a state we sometimes call healthspan.
The ultimate in life extension is to become immortal. We have previously discussed how you and I might attain immortality. We covered both high-tech and non-tech approaches. But these paths to immortality may strike you as improbable (if taken literally) or insufficient (if taken figuratively). In which case, you might settle for simply long life.
If so, you are in good company. George Burns’ How To Live To Be 100 advocates prunes and oatmeal, and it worked for him! But that’s only one book of the thousands that advise you how to have long life gracefully and happily. How about the science?
Scientific Approaches to Long Life
Medical science has not been asleep. But conducting research into long life is almost as complicated as understanding life itself. There are simply too many possible threads to unravel. For example:
- Achieve long life by defeating the diseases that most often end it: cancer and heart trouble.
- Promote healthy long life by tackling the diseases of old age, such as dementias including Alzheimer disease.
- Replace organs and body parts that wear out, with mechanical, lab-grown or donated substitutes.
- Substitute, or control the action of, genes that we believe limit long life.
Progress is so impressive that Google’s chief futurist guesses that by 2029, medical advances will add one more year, every year, to your life expectancy. You shouldn’t bet money on one optimistic prediction, but it’s nevertheless true: medical science is already making significant progress toward long life.
Three Radical New Ways to Address Long Life
Today’s blog is about none of the above. Instead, we’ll discuss three radical new approaches to achieve long life. They are superficially quite different, yet have an inner theme that unites them. Each is a long shot and not endorsed by the medical establishment. Nevertheless, each is the subject of ongoing research by bona fide credentialed scientists, and may turn out to change medicine’s understanding of how to achieve long life.
Here are the three paths being pursued for long life:
- Senolytics, meaning drugs that facilitate the removal of dead cells.
- Supplementing the diet with L-serine, a specific amino acid.
- Nutrition control, embracing calorie restriction, fasting and intermittent fasting.
The Zombies Within You
These three approaches are quite different, yet they relate to the same underlying problem: zombie cells.
Zombie cells, also called senescent cells, are a central feature of the problems of old age: arthritis, frailty and diseases like Parkinson’s and Alzheimer’s. Zombies are cells that no longer carry out normal functions, yet they are not completely dead. Therefore, the body does not clear them out and they accumulate. Animal studies have shown that removing zombie cells, or prompting the body to do so, can improve health and long life.
Senolytics Tackle Senescent Cells
Senolytics is a term coined by researchers at Mayo Clinic to describe drugs that target zombie cells. The Kogod Center on Aging at Mayo, led by Dr. James Kirkland, is conducting human studies using drugs that target senescent cells.
In the first published results, scientists treated 14 patients suffering from idiopathic pulmonary fibrosis (IPF), a progressive, fatal disease. The patients consumed two drugs for nine days spread over three weeks: 100 mg of dasatinib, an anti-leukemia drug, and 1250 mg of the natural flavonoid quercetin.
You might ask, why would anyone think that using an anti-cancer drug plus a nutritional supplement would be effective against a progressive dread disease? As far as we can judge, it’s something like this sort of thing:
- The underlying cause of IPF is thought to be cellular senescence.
- The Mayo team tested a wide range of drugs to see which ones successfully killed senescent mouse cells in the laboratory.
- The combination of dasatinib and quercetin, called DQ, turned out to be most effective against several types of mouse and human zombie cells.
Despite the small number of participants, this study was remarkably successful. Participants improved their physical strength and endurance, lung function and other measures.
Researchers plan additional studies using DQ and similar drugs to test whether they are so effective in clearing out zombie cells that they are able to combat some of the universal illnesses of old age, as our first new approach to long life.
Senolytics are a promising direction to address long life. However, at this time, there are many drug options to try, yet a limited understanding of their long term effects.
Note added February 2022: For more about the relationship between cell cleanup (senolytics) and dementia, see my later blog.
L-Serine, a Possible Secret of Okinawan Longevity
Fortune magazine recently highlighted yet another researcher pursuing the secrets of long life. Paul Cox is an ethnobotanist, a scientist who studies how native people use and consume plants. Yet he is also the leader of a privately-funded research lab looking at the long life potential of one of the amino acids, L-serine (empirical formula C3H7NO3).
How did he conclude that an amino acid that the body manufactures and uses naturally might also hide longevity secrets? It’s a long story (how long do you have?…)
- Cox studied the diet of the Chamorro people of Guam, hoping to learn why so many of them develop symptoms of both ALS and Alzheimer’s disease.
- He found that they catch and eat a local flying fox (fruit bat) and consider it a great delicacy. However, the foxes feast on the seeds of local cycad trees and accumulate in their bodies a neurotoxin called BMAA. Basically, the bats are highly poisonous.
- Trying to understand the poison, Cox hypothesized that BMAA might masquerade as an amino acid and be incorporated into protein chains in the brain.
- Further study showed that BMAA was imitating the amino acid L-serine.
- Cox hypothesized that neurological diseases like ALS and Alzheimer’s might be triggered by neurotoxins occurring in the environment, including BMAA.
- He reasoned that if BMAA does its mischief by pretending to be an amino acid, perhaps it could be countered by flooding the victim with that same amino acid. Cox conducted a study of vervet monkeys and showed that the poisonous effects of BMAA could be offset with a big dose of L-serine.
- A subsequent study of ALS patients showed that high doses of L-serine (30 grams per day) seemed to alleviate ALS symptoms. Continuing studies are looking at both ALS and Alzheimer’s patients.
From ALS to Longevity
- Cox then studied a village that seems immune to “old age” diseases – Ogimi, in northern Okinawa. He analyzed their diet, which emphasizes tofu and seaweeds. He found that the villagers consume more than three times as much L-serine as do typical Americans (8 grams/day versus 2.5 grams/day). Thus the L-serine could be one of the explanations for their remarkably long life.
Based on the ALS results and the Okinawa data, L-serine and perhaps other amino acids might help long life by protecting against neurological diseases. Analogy with the BMAA studies suggests that L-serine supplementation might protect neural processes from degradation. On the other hand, since Okinawans generally consume fewer calories than Westerners, their long life might also be a result of calorie restriction.
What’s the mechanism? If environmental neurotoxins operate by creating zombie cells, then L-serine may act by reducing the number of senescent cells that form. Thus it potentially acts to prevent zombies rather than to help clean them up.
Digression: Pharmaceutical grade, US-manufactured L-serine is readily available from The Serine Store. (I mistrust low-cost substitutes from overseas.) A 5-gram dose would bridge the gap between the US and the Ogimi diet. As a potential bonus, a study has shown that a 3-gram dose improves sleep quality. With the approval of our doctor Nola and I are trying one teaspoon (3.4 grams) as a dietary supplement before bedtime.
Fasting Casts Off Its Murky Origins
Now let’s talk about food. Not about eating food, but about not eating food. And I don’t mean starvation. I mean the choice not to eat food that we have.
Choosing not to eat comes in several forms, such as voluntary calorie restriction, complete or partial fasting and intermittent fasting. But let’s use fasting as a generic term.
After eons of searching for and chasing after food, how did we crazy humans get the idea of choosing not to eat food that we had? I have not seen a pre-history analysis, but we can at least trace fasting back to the Greek physician Hippocrates around 400 BCE.
Among the medical treatments recommended by Hippocrates was fasting: “to eat when you are sick, is to feed your sickness.” The ancient Greeks tried to learn by observing nature, and had noticed that most animals don’t eat when they are sick. It was not much of a stretch to believe that fasting might help a sick human too – especially since sick humans often just don’t feel like eating.
Fasting Becomes Religious
If fasting could restore health in a sick person, then it might confer benefits even to a healthy person. The Buddha advocated skipping the evening meal to convey feelings of “buoyancy and strength.” And there is hardly a religion that does not advocate fasting. In fact, religious fasting may pre-date Hippocrates: the Torah’s advocacy of “self-denial” during Yom Kippur is typically interpreted to mean not eating or drinking during the entire day.
Largely because of its religious connection, fasting is often considered to be an act of cleansing and holiness. For that reason, some modern diets have introduced limited fasting as a way to detoxify the body and promote its good health.
The further idea of fasting for long life seems to date to Luigi Cornaro, a Venetian living around 1500. At age 35 Cornaro’s health was failing due to gluttony, so he adopted a very restricted diet which he credited with giving him a long healthy life. (He died at 102, so it must have worked!)
Calorie Restriction Promotes Long Life
Scientific study of fasting for long life dates from the calorie restriction studies of 1935. Clive McCay and colleagues at Cornell University found that by limiting rats to 70% of their unrestricted food quantity, their lifespans were increased by 33%. They obtained the same results with guppies, spiders, protozoa, flies and yeast.
Why does calorie restriction encourage long life? We can address this question two ways: from a Darwinian survival-of-the-fittest approach, or in terms of molecular processes in the body.
The Darwinian answer is that low food availability causes an organism to postpone reproduction, waiting for better conditions. The animal puts its energy into maintenance rather than reproduction, and therefore lives longer.
However, the molecular mechanisms supporting improved long life are much less certain. A review article mentions several possibilities:
- A slower rate of cell division, discouraging late-in-life cancers.
- Less glucose in the blood, causing less damage to long-lived proteins.
- Fewer free radicals, thereby reducing damage to mitochondria.
Intermittent Fasting Also Supports Long Life
At this time, it’s unproven whether voluntary calorie restriction would lead to long life in humans. What is known is that reducing our calorie intake by 25% or more can lead to health problems, and moreover is viewed by many as “a way to extend life by making it not worth living.” For these reasons, today there is more interest in fasting, in particular intermittent fasting, which provides long life benefits with fewer downsides.
The word breakfast (break + fast) labels a meal that ends a night of fasting, when we are presumably sleeping rather than raiding the fridge. If you are not a continual nosher, you are in fact an intermittent faster.
Long life takes a long time to measure, but there are more immediate ways to see whether your body is responding to a brief fast. A mere 10 or so hours of fasting does not have much effect. However, a fasting period of 18 to 24 hours reduces blood insulin. This in turn increases lipolysis, the breakdown of fat. Intermittent fasting may also increase autophagy, a recycling of cellular material that relates in a complex way to cell senescence and aptosis.
These lengths of fast are not too impractical. After all, if you finish dinner by 7 pm and not eat until a 7 am breakfast, that’s a 12 hour fast. Skip breakfast and you can make it 16 hours. Skip both breakfast and lunch and you can manage a 24 hour fast.
Specific Intermittent Fasting Proposals
There are many proposals to incorporate fasting into the human diet with minimum pain and minimum risk to health:
- A 12-hour fast, 5 days in a row, carried out 3 times a year.
- The 16 to 24 hour fast referred to above. This is similar to “time-restricted feeding” in which all food is consumed during a 6 to 8 hour time period each day.
- The 5:2 diet – each week, on two non-consecutive days, you consume only 25% of your normal calorie intake.
No one knows whether any or all of these may support long life. Due to the lack of long-term studies on humans, no one should embark on a long-term fasting diet without guidance from a physician or nutritionist.
Note added 7/26/19: A news article reports new research indicating that eating only between 8 am and 8 pm can reduce hunger and control weight.
Three Pathways to Future Long Life
This discussion has touched on three approaches to long life. Each is a radical departure from studies that attract the biggest research dollars: defeating serious diseases, replacing body parts, and genetic manipulation. Each may turn out to be a dead end, with only limited practical application. Nevertheless, one or more of these may turn out to be part of an accepted future recipe for attaining long life.
What’s your attitude toward little-tested long-shot ideas for long life? How much evidence would you want to see before trying one of them yourself?
L-serine molecule adapted from Crystallography Open Database
Other images from pixabay.com:
– Watches by Couleur
– Skull / lightning adapted from ronymichaud and Clker-Free-Vector-Images
– Eating cookie by RyanMcGuire
– Herbs by kerdkanno