Breaking News! Exciting Discovery of a 2,000-year-old Tibetan Root

Last month, a group of geneticists from UC Irvine published an article about Rhodiola root, confirming that feeding it to fruit flies makes them live 20% longer, and reporting a negative finding about how that might  work:  benefits of Rhodiola appear to be entirely separate from the response to hunger, the “CR Effect”. Why was the article featured in the prestigious journal, PLoS One, which is targeted at a broad audience of non-specialists?


You might imagine that if living longer was as simple as eating an herb that has been known to traditional medicine since the time of the ancients, then this would have been validated by Science some time in the last hundred years, and health food store would be advertising it and every doctor recommending it.  Curiously, it hasn’t worked that way.  To study life extension in people takes too long, so a preliminary screening is done in mice.  To test a single candidate treatment costs about $100,000 and takes over two years.  Because herbal medicines can’t be patented, there is no company motivated to put up the money, and aging has never been a high priority for government grants, and the Federal budget for science has been dwindling.

(Stephen Spindler of UCLA has taken on the project of testing dozens of compounds to see if they extend the lives of mice, and has advocated that it’s just too slow and expensive, and we might gather information more quickly and cheaply by looking at how the compound effects the mouse’s gene expression.  This is expected to work because we know that gene expression changes in some characteristic ways in older mammals, and this is thought to be causally connected to aging.  Is anyone asking, “Why don’t we try to artificially engineer a youthful profile of gene expression?” Well, yes …but that’s a digression for another column.)

Only a handful of compounds are known that have been documented to extend life span in mice:  Deprenyl, metformin, melatonin, and rapamycin are three that come to mind.  They are all prescription drugs.  Melatonin is widely-available and cheap, useful for regularizing sleep and adjusting to change in time zones.  Metformin is a genuine anti-aging compound, in my opinion.  Its benefits are clearest for people who are overweight or diabetic; though I am neither, I take it myself, in subclinical doses.  Rapamycin is not ready for prime time.  It is a powerful immune suppressant and its long-term effects in humans have not yet been charted.  Deprenyl (= Selegeline,Eldepryl, Emsam, or Zelapar) has been around for decades and its side-effects are better charted.  It is a stimulant, a cousin of methamphetamine, and it will change the texture of your experience, in ways that you may like or may not.  A fourth compound is a Vietnamese herb called dinh lang, for which I’ve been able to locate just this one intriguing study from 1992.

Fruit flies are much easier to breed and quicker to produce results.  The tradeoff is that they are more distant from humans.  It’s a striking and quite general finding from the science of aging in the last 20 years that genetic mechanisms of aging tend to be similar, conserved over great stretches of evolutionary time, so that there is reason to hope that a genetic pathway that affects aging in flies will have a corresponding pathway in people.  There are more compounds known to extend life span in flies, and studying them for potential human therapies is one more promising, underfunded research project.  Stem Cell 100 is a product that claims to induce very long life span in flies in experiments also conducted at Irvine.  I’ve asked, but have been unable to find any peer-reviewed confirmation of this claim.)


The herb Rhodiola has a venerable history

Rhodiola has a legendary history dating back thousands of years. In 77 A.D., the Greek physician Dioscorides documented the medical applications of the plant, which he then called rodia riza, in his classic medical text De Materia Medica. The Vikings depended on the herb to enhance their physical strength and endurance, while Chinese emperors sent expeditions to Siberia to bring back “the golden root” for medicinal preparations. The people of central Asia considered a tea brewed from Rhodiola rosea to be the most effective treatment for cold and flu. Mongolian physicians prescribed it for tuberculosis and cancer.   (Herb Wisdom)

The new paper starts with a quick summary of what is known about Rhodiola from modern experiments with animals.  Reading it, one might garner the impression that experiments have been haphazard.

The root extract of Rhodiola rosea, also known as the golden root, has been widely used in traditional and integrative medical practices in Europe and Asia, where it has been purported to mediate a variety of beneficial effects in humans, such as improved mood, improved physical and mental stamina, and enhanced protection against high altitude sickness [1]. The extract has also been reported to protect against tumor progression in mice, improve endurance in rats, improve blood glucose profiles in diabetic mice, and protect snail eggs against oxidative stress, heat, and heavy metals [2][5]. Our group has previously reported that R. rosea can extend the lifespan of the fruit fly, Drosophila melanogaster, protect flies and human cultured cells against oxidative stress, and decrease the production of reactive oxygen species in isolated fly mitochondria [6][8].

(Does the prose remind you of the Findings page from the back of Harpers magazine?)

Why we might raise an eyebrow

The authors of this paper raise the possibility that Rhodiola ought to be of interest for further investigation whether it might be a candidate for human life extension.  There are two reasons for optimism.

 First: Treatments that extend life span almost always increase stress resistance as well.  Animals that are pre-treated with caloric restriction prove to be much hardier when exposed to toxins.  Any compound that increases stress resistance becomes an interesting candidate for experimental investigation for life extension potential.

In one experiment, mice were exposed to a 100% lethal dose of gamma radiation..  But among those mice that were prepared with Rhodiola 30 minutes beforehand, 90% of them survived the same treatment.  The mechanism for such a dramatic protection is not completely understood.  The gamma radiation acts like the proverbial bull in the body’s china shop, randomly breaking apart the delicate and complex molecules on which life depends.  It’s unlikely that Rhodiola can do anything to stop that process.  However, the body has its own chemical machinery for repairing the damage, and it is likely that these are upregulated in response to the Rhodiola.  This makes sense at least on the surface, but it leaves you wondering:  if there is such a survival advantage to enhanced presence of these repair enzymes, why does the body wait until it sees Rhodiola in order to produce a little extra?

Second: Most of the known interventions that extend life span in animals have proven to be related to the biochemical pathways that the body uses to resist stress and stave off aging during periods of starvation.  CR mimetics are chemical or other means to harvest this potential without suffering hunger.  But the potential for using these is in danger of become saturated in humans because we already have several good ideas for mimetics.  Already 8 years ago, Aubrey de Grey was warning us that caloric restriction works much better in short-lived animals than in long-lived animals, and that the potential for extending human life by eating less (and mimetics) might be limited.

Bottom line

Rhodiola is interesting for all these reasons, and the fact that it is reported to increase energy, enhance concentration, and counter depression has tempted me to try it.  I’ll let you know.

Dietary Salt: Medical Science Corrects a Long-Standing Error

The Federal Center for Disease Control (CDC) commissioned a review of the health benefits of reducing salt intake, and a draft of the final report is available on line.  The take-home message is that salt, in the quantities consumed by most Americans, is no longer considered a substantial health hazzard.  The average American eats about 1½ tsp. per day.  What the CDC study reported explicitly is that there is no benefit, and may be a danger, from reducing our salt intake below 1 tsp per day  But even above 1 tsp, the evidence is tenuous and inconsistent.  It may be that we’re better off with more salt than less, up to 2 or even 3 tsp per day. How did it happen that such standard medical advice drifted astray, then went un-corrected for so long?

This review by the National Academies Institute of Medicine (IOM), commissioned by CDC, considered dozens of studies, from cross-cultural (less reliable) to prospective, randomized with control (most reliable).  Most studies showed no relationship between salt intake and any health outcome.  Some seemed to indicate that more salt had a beneficial effect.  Gina Kolata of the NYTimes published an excellent summary of the report a few weeks ago, and I won’t try to improve on her article.  Here’s an excerpt:

One 2008 study the committee examined, for example, randomly assigned 232 Italian patients with aggressively treated moderate to severe congestive heart failure to consume either 2,760 or 1,840 milligrams of sodium a day, but otherwise to consume the same diet. Those consuming the lower level of sodium had more than three times the number of hospital readmissions — 30 as compared with 9 in the higher-salt group — and more than twice as many deaths — 15 as compared with 6 in the higher-salt group.

Another study, published in 2011, followed 28,800 subjects with high blood pressure ages 55 and older for 4.7 years and analyzed their sodium consumption by urinalysis. The researchers reported that the risks of heart attacks, strokes, congestive heart failure and death from heart disease increased significantly for those consuming more than 7,000 milligrams of sodium a day and for those consuming fewer than 3,000 milligrams of sodium a day.

To translate this last study into teaspoons: the finding was that anything between 1½ and 3 tsp of salt per day is just fine, and there were adverse effects from eating more than that or less than that.  Most Americans who are not consciously restricting salt fall in this range (1½ to 3 tsp).  People who are on low-salt diets for medical reasons are getting as little as ½ tsp, and they’re well into the range where dearth of salt is harming them.  The worst impact of low salt is on insulin sensitivity. Loss of insulin sensitivity is a big risk factor for all the diseases of old age.


Comments and Context

Perspiration is the biggest source of variability in individual requirement for salt.  Given that our need for salt varies widely with exercise and with temperature, it’s surprising that most of the studies proceeded blindly with a “one-size-fits-all” model.  A few tested for salt excreted in the urine, which is a better measure than the amount consumed.

The IOM finding was heralded by a great number of alternative web health sources which have told us for years that salt has been falsely demonized (Dr Mercola, Dr Weill, Adele Hite)

How did the medical community fall into such a large error, lasting so long?  The medical research community gets a lot of things right, and when they make major errors, you can usually see the trail of money leading them astray (Vioxx, hormone replacement therapy…).  But there was no Pharma Giant making hay from people who ate less salt, so how did this happen?  I have a personal theory:

Blood Pressure and Clogged Arteries – Chicken and Egg

The central problem (I believe) is that the causal association between salt and heart disease was and still is based on faulty logic.  The error is in the connection through blood pressure as an intermediate variable.  The new review does attempt to look for direct evidence of a link between salt and CVD (cardio-vascular disease), independent of blood pressure, but the IOM review also echoes the faulty reasoning, perpetuating the old error.

As Kolata writes: “Until about 2006, almost all studies on salt and health outcomes relied on the well-known fact that blood pressure can drop slightly when people eat less salt. From that, and from other studies linking blood pressure to risks of heart attacks and strokes, researchers created models showing how many lives could be saved if people ate less salt.

Here’s the logical fallacy:  High blood pressure is associated with increased risk of heart attack.  Salt causes blood pressure to increase.  Therefore, (the community consensus concludes), salt increases the risk of heart attack.  The problem with this thinking is an example of the old warning, “correlation is not necessarily an indication of causation.”  In this case, there may be no causation at all.  Here’s why:

Atherosclerosis is the most common precursor to heart disease.  In atherosclerosis, arteries lose their elasticity and also become clogged with inflamed fatty deposits. The deposits can break off and block blood flow.  If this happens in the brain, the result is a stroke, and if it is in a coronary artery, the result is a heart attack.  So we understand why atherosclerosis implies a big risk of heart attack and stroke.

It’s also true that atherosclerosis causes elevated blood pressure.  This is a simple mechanical effect.  When you have a narrower tube, it takes more pressure to drive the fluid through it.  Atherosclerosis causes high blood pressure and also causes risk of CVD.  And most people are subject to atherosclerosis as we age.  So it’s no mystery that high blood pressure should be correlated with CV risk.  But that doesn’t mean that high blood pressure causes CV risk.

Eating salt causes the body to retain water, and the swelling increases ambient pressure in surrounding tissues, and blood pressure increases in response.  So salt increases blood pressure and atherosclerosis increases blood pressure, but they work via two very different mechanisms.  There’s every reason to believe atherosclerosis causes CV risk, but no reason to think that salt should lead to CV risk, even though it increases blood pressure.

It’s clear from epidemiology that atherosclerosis is correlated with blood pressure.  It’s clear from simple physics that atherosclerosis causes high blood pressure. (A => B.) But maybe there’s a causal link in the other direction as well (B => A).  This is what doctors and medical researchers have long assumed: that high blood pressure causes a mechanical strain in the arteries, and that in some unexplained way the body’s response is atherosclerosis.  It’s a long-standing theory.  And if it is true that B causes A, then of course we’d have reason to think that salt, which raises blood pressure, would also increase severity of atherosclerosis.

This hypothesis (B =>A) was first confirmed in an experiment on rabbits in 1989.  The experiment seems questionable, with hindsight.  Perhaps the researchers were looking too hard for  evidence to support an important and popular theory, and they were fooled by confirmation bias.  This is the well-studied tendency of all of us – with and without scientific training – to easily take in new information that fits well with what we already know, but to ignore or cast aside information that doesn’t fit with our existing beliefs.  When experiments don’t turn out the way we expect, we take it as a failure, and often we try to “fix” the problems, until the experiment “works”.

The 1989 study was by a senior team of researchers at Boston University, headed by Aram Chobanian  (who subsequently served as University president). They operated on young rabbits, removing one kidney and constricting blood flow to the other with a tight-fitting band around the artery.  About half the operated rabbits developed hypertension, and the other half either died or were excluded from the study.  The remaining rabbits, all of whom had high blood pressure, developed atherosclerosis – the result they were looking for.  The Chobanian study made a big splash, and has been cited hundreds of times since 1989.

But could it be that the experiment came out the way it did for a different reason entirely?  (This is my own thought, and I haven’t seen it in print.  You’re the first to read it.)  Restricting kidney function can lead quite directly to atherosclerosis, independent of the blood pressure connection.  Atherosclerosis is known to be elevated in kidney dialysis patients.  A 2011 study comparing autopsies of heart patients and dialysis patients found that the arteries of the dialysis patients were even more clogged than those of the heart patients.  This is not B=>A but K=>A.  Maybe the idea that B=>A has been a long detour into the wilderness.

Surveying web sites that offer the best in standard medical advice, I’m surprised to see that all of them embrace the logic (B=>A) without any acknowledgment that (A=>B) is the expectation of elementary physics, and that evidence for (B=>A) is tenuous and indirect.  None of them have yet updated their advice on salt to comport with the newly-recognized reality.

Crystal Ball

Given what we know about confirmation bias, it was rather brave of the IOM to report conclusions that were at odds with medical advice of the last 50 years.  Officially, the recommendation to reduce daily intake below 1 tsp has been lifted, but some of the studies cited seem to show that our bodies need more than this to avoid impaired insulin sensitivity.  Now that IOM has made it respectable to take a different view of salt, we can expect a sea change in the medical establishment’s attitudes toward salt, as the force of confirmation bias has been shifted to the other side of the scale.

How to be skinny

We know that cutting calories has multiple health benefits and makes you thinner. But suppose we play tricks to be thinner without eating less – is there still a benefit for health and longevity?  This week we review Irvingia, Metformin, Pycnogenol, Green Coffee Extract, Acarbose, and old-fashioned amphetamides for weight loss. Also avoiding carbs and increasing fiber, intermittent fasting and bursts of exercise before eating.

Weight loss drugs have a bad name from the days when people were a little too eager to lose weight for appearance’s sake, and willing to take risks with their health to do so. Early weight loss drugs were stimulants, with all the associated risks: they make you feel good, they keep you from sleeping, they let you down, they’re habit-forming. Now we know that keeping weight down is an increasingly important part of staying healthy as we age. There is a new generation of drugs and supplements that work through different channels than the old ones, and some of them have long-term benefits independent of weight loss.

I’m coming from a perspective based on the loss of insulin sensitivity as a primary driver of aging. This is the essence of “metabolic syndrome” or “Type 2 Diabetes”, but in a milder form, this is a part of how we all age. Loss of insulin sensitivity causes us to gain fat cells, which exacerbates loss of insulin sensitivity in a vicious cycle. Metabolic syndrome, even in its mild form, is associated with increased risk of cancer and heart disease.  Simply eating less is the best medicine in principle, but a large majority of people who start off well by applying willpower end up actually gaining weight. [ref1ref2]   Hence there are tricks and treatments, strategies and diet fads. My advice (as usual) is to recognize that diet is very individual, to try different diets and diet aids until you find something that works for you. Here’s a brief guide to what’s available.

Green Coffee Extract

Note added in 2015:  I have become aware of fraud in the science behind Green Coffee Extract, and I no longer know whether I can recommend it.  Here is the article with retraction notice.
This is the latest among the new generation of supplements that affect the insulin metabolism. GCE slows the absorption of sugar and reduces the secretion of the enzyme (amylase) that turns starches to sugar in the digestive tract, and also blocks the enzyme glucose-6-phosphatase that makes sugar in the liver. Overall less of the food energy passing through the intestine is absorbed into the body, and to this extent taking green coffee extract should be expected to have the same benefit as eating less.

The primary active ingredient may be chlorogenic acid, but its effect has not been separated from other phytoesters included in the extract. The extract contains no cafeine*. In the best results to date, subjects lost an average 8 kg over 22 weeks, without consuming less calories.  A 2011 review (before this latest study) found clear evidence that GCE is effective as advertised, but bemoaned the fact that all the research in the field was linked to companies that stood to pofit from the sale of GCE.

Chlorogenic acid is also found in sunflower seeds and prunes.

Leptin is a hormone that signals your brain that you’ve had enough to eat, and signals your fat cells to burn up their fat stores. As we age, we lose sensitivity to leptin (as to insulin). Irvingia is the extract of an African bush mango, purported to increase leptin sensitivity.

There are reports of large weight loss in a short time with irvingia, [ref1, ref2] ,  but the studies are short-term and there are ambiguities in their design, so results are often summarized by reviewers as “inconclusive”.  [ref1, ref2]

Other ways to prepare the insulin system before eating
There are several other foods reported to help prevent the insulin spike from a meal, when taken 20 before eating anything else. These include cinnamon, vinegar, and grapefruit.

Lowers blood sugar after eating, effectively improving insulin sensitivity. This is a supplement in the same class as others mentioned here, and may offer long-term health benefits including longevity, but no effect on weight reported.

Previously reported on this page, metformin is a prescription drug that has been the treatment of choice for diabetes for over 40 years.  It lowers cancer risk so effectively that we speculate it might be useful for non-diabetics as well. Weight loss from metformin is primarily by appetite suppression. Blood sugar is lowered by metformin, and yet people feel more satisfied and eat less. The reported weight loss in studies of metformin is modest compared to irvingia, but it tends to stay off (irvingia studies are all short-term) and the studies are well-controlled. [ref]

This is a prescription drug that slows sugar absorption from the stomach, mimicking a low-carb diet without restriction of carbs. It is effective in avoiding diabetes, and shifts the body toward a “younger metabolism”. But no weight loss has been associated with acarbose, perhaps because the slow sugar absorption leads to slow signaling of satiety.

Other tricks to lose weight
Exercise is #1. A few minutes of exercise just before eating signals the body that “this food is to be burned, not stored”.  Intermittent fasting has been mentioned in this column, and works for some people. Filling the belly with high-fiber food is a favorite trick of mine. I eat mountains of green leafies, and half a cup of raw wheat bran every day. It’s my impression that wheat bran has “negative calories” in the sense that food goes through me faster and less of it is absorbed when I eat large quantities of bran. (I have seen no studies on this, and have only my personal experience to report.) I suspect that nutrients are adsorbed on the bran and excreted with the stool, so I try to take my supplements in a different meal from the bran. I’ve adjusted to bran and it doesn’t give me the runs, but, not to put too fine a point upon it, let’s just say that I don’t worry about constipation.

The most promising of the new generations of supplements that affect absorption of calories are green coffee extract and irvingia. Weight loss from the two seem to be large and of similar magnitude. And the evidence for both suffers from suspicion that the researchers had financial ties to the companies that sell these products. (Someday, I want to live in a country where taxes pay for independent medical research, so that we all have unbiased information about foods and drugs that is not linked to their sponsors.) In addition to aiding with weight loss, both are likely to have positive long-term benefits for health and longevity.

Metformin has the disadvantage of being available only by prescription, but it is better-studied than either of the two supplements, it has been around for 50 years, and is known to be safe and effective. It works by a slightly different mechanism, but is also likely to produce supplementary benefits for long-term health.

There is a huge amount of individual variability in all these studies. It makes sense to experiment on yourself to learn what works for you. You can’t judge by your weight loss from one day to the next, because that is dominated by water retention and salt intake. But if you weigh yourself daily in the morning and stick with a trial for at least two weeks, you will be able to tell what is working and find a program that’s effective, and that you can live with.

* Cafeine may have benefits and costs for insulin sensitivity as well as costs for cardiovascular health. Many epidemiological studies have identified a net effect of lower mortality rates in people who drink modest amounts of cofffee.

Short Takes from the 2013 AGE meeting, Baltimore June 1-3

I’ve been at the annual meeting of the American Aging Association this weekend. Here are some brief take-home messages from the presentations I’ve attended.

Growth Hormone

Several talks involved growth hormone one way or another. Growth hormone is hyped as an anti-aging remedy by many supplement sources, but its benefits are likely to be short-term, and there is substantial risk that it actually increases mortality risk in the long run. Holly Brown-Borg made this point quite explicitly. Her research is centered on two strains of mice, a dwarf strain which has a genetic defect for growth hormone, and lives 50% longer, the other is genetically engineered to have extra growth hormone, and it lives 50% shorter than ordinary lab mice. The dwarf mice are super-healthy and don’t get cancer, but you can make them sick by giving them growth hormone.

Ames Dwarf Mouse

Ames Dwarf Mouse

Valter Longo reported on his research with the little people of Ecuador. Their distinctive genetic endowment is called GHRD for “growth hormone receptor deficiency”. They never get cancer, and have lower rates of cognitive decline with age. Many of them love to eat and drink, and despite their habitual Bachanalia, maintain their insulin sensitivity with age and don’t get diabetes. Many people enjoy the effects of HGH in the short run, and like what it does to their body image, but it’s likely to be pro-aging in the long run.


Greg Fahy is knowledgeable, innovative, courageous, and looks 15 years younger than his chronological age, and is my friend as well as colleague in this field. He suggested that a short course (<1 year) of HGH might be used to regrow the thymus, and is seeking funds for a pilot experiment with ten subjects, age 50-65. The thymus is a small organ behind the breastbone that trains our white blood cells to distinguish “self” from “invader”, and which shrinks steadily over our lifetimes. “Thymic involution” is closely associated with aging of the immune system. If Greg is able to follow through, I’ll let you know how this works out.


Blueberry Man comes to these meetings, and cites dozens of studies for diverse health benefits from eating blueberries. He talks about being on crutches with degeneration of his joints a few years ago, from which he recovered completely after starting to eat two cups of blueberries a day.


The research of Eric Smith is centered on glutathione, and its precursor, a gene called nrf2. Glutathione is an anti-oxidant working throughout every cell, detoxifying especially the liver. We need glutathione more as we get older, but our bodies make less of it. Centenarians and people on calorie restriction both have more glutathione than the rest of us. In genetically modified animals, glutathione is associated with longevity. I have been down on dietary anti-oxidants in the past, but I believe that up-regulating our own glutathione is a good thing for longevity. Unfortunately, we can’t take a glutathione pill. It doesn’t make it through the digestive system, and it doesn’t last in the body, as it is continually being used and recycled. There is a supplement called NAC (n-acetyl cysteine) which is a biochemical precursor, and some people take it to try to induce the body to make more glutathione. SAMe has also been demonstrated to increase glutathione levels. Nrf2 is a gene important to the synthesis of glutathione, and there is a commercial mixture of herbs called Protandim that purports to stimulate the body’s production of nrf2. Interesting to me is that the first ingredient in Protandim is also the first ingredient in Product B, which I take as a telomere activator. That is silymarin, or milk thistle.


This is a prescription drug that slows the body’s uptake of sugar, so blood sugar doesn’t spike after a high-carb meal and then plummet back down afterward. I believe these cycles are related to the loss of insulin sensitivity that is a common characteristic of human aging, leading to diabetes and higher risk of all the diseases of old age. I have heard of many treatments to promote insulin sensitivity, and promise to do some reading and write a post about these herbs and drugs soon. In the meantime, there’s background in my article on metformin.



In 2009 came a sensational report from David Harrison’s group at Jackson National Labs. Mice received a short course of rapamycin late in life, and still showed a 15% life extension (measured from birth). Researchers have been excited about its anti-aging potential, and in three short years, there have been 10 more studies documenting life extension up to about 25% in various strains of mice. There were several major presentations at the conference focused on rapamycin. Rapamycin binds to two sites, called TORC1 and TORC2 (TOR stands for “target of rapamycin”). Joe Bauer reported his theory that TORC2 holds most of the benefits, and TORC1 most of the dangers of rapamycin, and he is working to separate the two effects. Arlan Richardson offered an hour-long advertisement for rapamycin as a cancer treatment, for cardiac health and prevention of cognitive decline. He reluctantly admitted that it also causes cataracts, slows healing, and contributes to Type 2 diabetes. Conference consensus (including this author) is that rapamycin is an exciting new vehicle for studying aging, but as a general tonic, it’s not ready for prime time.

Dueling Monkeys

There have been two ongoing studies of caloric restriction in rhesus monkeys, at University of Wisconsin (UW) and at National Institute of Aging (NIA). Last year and the year before, these two groups came out with their preliminary conclusions from the 25-year project. Newspapers picked up the UW results, and reported: CR Study in Primates Shows Positive Results! The next year, the NIA report was summarized: CR Study in Primates Shows Negative Results! At this meeting, Julie Mattison of NIA and Roz Anderson of UW charmed us with a well-coordinated presentation seeking to clarify the differences between the two studies. Both studies found that the CR animals were healthier, suffered less disease, were more active and looked better than the control animals. (Interesting that Sai Krupa Das summarized the CALERIE study <of CR in humans with almost the identical words.) Both studies found no difference in overall schedule of deaths in the two groups. But when they separated aging-related deaths from accidental deaths, the UW group reported that there was a big difference, with CR animals living far longer on average. Meanwhile, the NIA group reported that there was little difference between the life spans of the two groups. Some of the difference is due to the fact that the UW diet was heavier in sugar, and monkeys assigned to the control group got to eat as much as they wanted. Meanwhile, the NIA group fed both groups of monkeys more protein, less fat, and complex carbs instead of sugar. They also limited the food intake of the control monkeys (though, of course, they ate more than the CR monkeys). It’s still not clear that these are the crucial differences between the two results, and since the total number of monkeys was so small, it is conceivable that the difference was only a statistical fluke.

Fasting before Surgery or Chemotherapy

Calorie restriction not only increases life span but dramatically improves resistance to many kinds of stress. Valter Longo had the idea that it might help the body to withstand the shock of chemotherapy. What he found was promising beyond his expectations, but resistance among doctors and patients has been frustrating to say the least.

I’ve known Valter Longo for 10 years, since he had to work like heck to convince the biology community that yeast cells commit suicide, for altruistic reasons. In the 1990s, he proved that yeast colonies, when starved, partake of a remarkable adaptation in which 95% of them commit suicide, digesting their cytoplasm into food for the other 5%. Most curious is the fact that these animals are genetically homogeneous. How do 5% of them choose themselves as survivors? How could such an adaptation evolve, when there’s so much motivation to “cheat” and bias the odds to be among the 5% beneficiaries rather than the 95% martyrs?

 Longo has worked the last several years to establish that fasting before chemotherapy (and radiotherapy) doubly pre-conditions the body. Cancer cells become more sensitive to the chemo, and are killed with more certainty. Meanwhile, the rest of the patient’s cells become less sensitive to chemo, and they survive the insult much better. Patients who fast before chemo report that their nausea and fatigue are greatly reduced. At first, Longo found it was a tough sell to get patientswho are willing to try fasting for two to three days before chemo. Even tougher was the opposition from oncologists, who not only advised against the procedure, but (in the worst cases) found that their patients’ blood sugar was “too low”, and put them on intravenous sugar before chemo! But in the last three years, his idea has taken off, and there are now many, many chemotherapy patients in which the technique has been successful.

 James Mitchell of Harvard reported on parallel work with mice, demonstrating that pre-conditioning with fasting protects mice against surgical trauma, dramatically reducing risk of death and improving recovery time. He also experimented with reducing protein only, making up the difference with carbohydrates, and was able to get much of the same protection. Combining calorie restriction and protein restriction worked better than either separately. Mitchell recommends fasting, or perhaps juice fasts before surgery of any kind, except if the patient is frail or emaciated to begin with.

The title of his paper was “Calorie restriction and essenial amino acid restriction contribute additively to the benefits of short-term dietary restriction in mice.” Previously, there had been a lot of speculation whether the mechanism by which calorie restriction worked was really just that the animal was starved of protein, and the mechanism by which protein restriction worked was that the animal was just starved of one essential amino acid (usually methionine). This was the first demonstration I have seen that the effects can be separated, and the benefits of both calorie restriction plus methionine restriction are greater than the benefit of either restriction separately


I’ve been attending these meetings for several years, and I continue to find that the meetings are small, there are almost no MDs, and the research seems to occupy a backwater between bench science and medical research. Compared to cancer research or heart or lung disease, the field is way underfunded. Still, research in anti-aging medicine is growing, as policy-makers realize it is a way to address many diseases of old age with a powerful new paradigm.

 For basic information about healthy living for a long life,
see the author’s permanent page at