Benefits of Intermittent Fasting With Valter Longo, Ph.D

Interview With Valter Longo About The Benefits Of Fasting 

Fasting has been promoted for various reasons for centuries, but it’s only recently that researchers have been able to investigate the health benefits from doing strict fasting for days at a time.

Fasting is thought to induce various changes in the body that help protect the cells from damage that may occur from the environment, and trigger pathways in the body which may increase health and possibly lifespan.

My own experience with fasting

Fasting is something that I’ve done over the years in many forms. I’ve restricted my eating to only a few hours of the day and had long periods where I didn’t eat for up to 16 hours. I’ve fasted for one day of the week for 24 hours for many years. I’ve found that fasting seems to me mentally, to help me focus better.

It was always difficult to objectively tell whether or not fasting was helpful to myself, because I’ve done calorie restriction for such a long time, and this by itself has very good results in terms of improving health markers and improving health.

Fasting has always been pretty easy to to do for me, but I’ve found calorie restriction to be just easier. Not only that, calorie restriction has a lot more data to back up the health and longevity benefits.

There is no doubt that fasting is beneficial to health, but it’s still up for question whether or not it can really extend lifespan significantly without any reduction in calories. That being said, people who fast, may automatically have their caloric intake reduced anyway.

 

The Interview

Dr. Rhonda Patrick speaks to Valter Longo, who was a student of the calorie restriction researcher and pioneer Roy Walford. During the last few years, he has demonstrated that prolonged fasting is able to rejuvenates the immune system so that it is in a more youthful state, as well as induces anti-cancer effects, and helps prevent side effects from cancer therapies in humans. He also mentions how fasting may improve the health or even cure people with autoimmune diseases such as multiple sclerosis. I’ve previously shared one recent study showing how fasting rejuvenates the immune system.

Valter Longo has recently written a book which is not yet available in English. I was just made aware that an English version of his book The Lonevity Diet will be available in January 2018. I’ll be sure to write a review of it when I receive a copy.

Related articles: Is fasting good for you?

Calorie Restriction Diet in Rhesus Monkeys and Humans

Calorie Restriction Diet in Rhesus Monkeys and Humans

Since the 1980s researchers have been conducting an experiment on rhesus monkeys by restricting their calories to see if a calorie restriction diet is beneficial in improving their health and ultimately slowing down ageing, as it does in other species such as yeast, worms, flies, spiders, rats, mice, dogs, cows, among others the diet has been tested on.

Rhesus monkeys live around 27 years on average, and are thought to be the most similar physiologically to humans  — so it’s believed the results would be more translatable to humans. Pending the final results, I’ll go into what the current findings are, what they could mean, and whether or not the work is likely to be translatable to people.

A/B is the monkey eating a standard diet. C/D is the monkey that has been put on calorie restriction. As you can tell, the monkey on calorie restriction looks much younger and is also expected to live longer
A/B is the monkey eating a standard diet. C/D is the monkey that has been put on calorie restriction. As you can tell, the monkey on calorie restriction looks much younger and is also expected to live longer

ISCONSIN RHESUS MONKEY CALORIE RESTRICTION DIET STUDY

The study began in 1989 where they introduced 30 male rhesus monkeys into the study and then a further 30 females and 16 males in 1994. The animals were randomised and then put into either the control group or the calorie restricted group.

Restriction of calories was done in phases: 10% reduction in calories based on individual primate ad lib caloric intake until they reached 30% restriction. Unlike the NIA study, this ad lib group were allowed to eat as much as they wanted.

The animals also received very good care and any conditions that developed during the study would be treated. The median survival for rhesus monkeys in captivity is about 26-27 years and a maximum lifespan of 40 years, with 10% reaching 35 years of age.

In 2009 we got a glimpse that calorie restriction in non-human primates seems to work and extends both healthspan and lifespan (1). Age-related mortality was slashed and control fed animals were 3-times more likely to die of age-associated diseases than the restricted monkeys; although at this point all-cause mortality between groups did not reach statistical significance.

The calorie-restricted animals were far healthier with a complete protection from diabetes; they also had less heart disease, fewer rates of cancer, less muscle loss with age, less brain atrophy, among other benefits. It has been reported that the calorie restriction monkeys also look a lot younger than their well-fed counterparts.

WNRPC rhesus monkey survival2014

An update came in April 2014: The Calorie Restriction diet improved all-cause mortality and age-related mortality in primates (2). Age-related mortality includes deaths from cardiovascular disease, cancer, diabetes, arthritis etc. All-cause mortality takes into account deaths from accidents, anesthesia, gastric bloat (accidentally caused by overcooked batches of food), and endometriosis (a non fatal human disease). Most of these may have been preventable deaths and were not caused by intrinsic ageing and so a separate analysis for just age-related mortality was created to look at the effect of CR on deaths caused by ageing and the diseases that are associated with it.

So far 63% (24/38) of the control animals have died from age-related causes compared to only 26% (10/38) of the calorie restricted group. This indicates that simply reducing calories can have a dramatic impact on the incidence of diseases with age.  For all-cause mortality, the control group had 1.8 times the risk of death from any cause compared to the CR group. Right now there are currently 12 CR monkeys a and only 6 control fed animals alive.

Rhesus monkeys, left to right, Canto, 27, on a restricted diet, and Owen, 29, a control subject on an unrestricted diet, are pictured at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison on May 28, 2009. Photo: Jeff Miller Date: May 2009
Rhesus monkeys, left to right, Canto, 27, on a restricted diet, and Owen, 29, a control subject on an unrestricted diet, are pictured at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison on May 28, 2009. Photo: Jeff Miller
Date: May 2009

CR ‘anti-aging’ protocol: Although calorie restriction has improved average lifespan in the study at WNPRC, the effects of the diet on the monkeys metabolic, lipid and hormonal profile has been inconsistent with the changes that are observed in mice, rats and humans. Reasons for this could be that the reduction in calories was not sufficient to signal low energy availability to activate the pathways and responses that are involved in retarding ageing in mammals. However, even with the inconsistent results, the monkeys still benefited from a reduction in calories and stayed leaner, healthier, and younger for longer.

table

A sweet disaster: To understand why there might have been a longevity advantage in the CR group relative to the control group, even though the CR monkeys did not display the CR-phenotype, we have to take a look at the diet used in the study. The monkeys in the Wisconsin study were fed a semi-purified diet which comprised of 65% carbohydrates with 28.5% coming from sucrose and the remainder from cornstarch vs the NIA study where the monkeys chow comprised of 56% carbohydrates with only 3.9% coming from sucrose (3).

The high level of sucrose in the diet that the Wisconsin monkeys received could explain why there were more cases of diabetes in the controls of this study compared to the NIA controls; although interestingly there were two cases of diabetes in the young onset monkeys in the NIA study whereas the WNPRC study reported a complete protection from diabetes in the CR animals. Also, although blood glucose levels were lower in the WNPRC monkeys, they had very high levels of insulin in the controls and the CR diet brought it down to more appropriate levels.

In contrast with the NIA monkeys which had lower levels of insulin but slightly higher levels of glucose. Before the monkeys began the diet, they were monitored for a 3-6 month period to assess their caloric intake when they had free access to food so that the researchers could establish an individual baseline from which to reduce the calories from. Given that high sugar diets stimulate appetite, the monkeys ate a generous amount of food during this period. Later in the study the researchers found that the difference between the calorie restricted group and the control group dwindled to only 18% difference because the monkeys in the control group voluntarily reduced their calorie intake. Monkeys normally do this with age, but this was fairly early in the study, so the researchers lowered the intake of the CR group further to establish a 30% difference once again. Although there were some exceptions, as not all monkeys had their intakes reduced further because of the appearance of the animal and was deemed too risky to the animals health. No further reductions in calorie intake in the CR group is being performed at this stage of the study, even if control animals still continue to decrease their intake in old age.

It was reported that 5 of the 38 monkeys of the Wisconsin control group developed full blown diabetes vs only 5 out of 64 in the NIA control group (11% vs 8%). Diabetes incidence does have a strong correlation with increasing weight. The NIA monkeys weighed less at all ages than the WNPRC monkeys. (2). In humans, the prevalence of diabetes (diagnosed) in the UK is as high as 5.8% in England, with the national average at 4.6% in 2013 (4). Earlier reports say at least 12% of deaths in the UK are a result of diabetes and its complications. This means that the control group in this particular study represents more closely a typical western population  in terms of diet and disease incidence.

controlvsrestricted-1-

Longevity phenotype: A lot of research has gone into the biology of ageing in recent years. What is clear is that there is a specific phenotype that is common among long lived individuals and families. Typically, they will have low levels of glucose and insulin. (diabetes cases being rare in those who reach 100). Studies have shown a decreased functioning of the IGF-1 receptor and/or decreased levels of IGF-1 levels — which could be achieved by lowering protein intake to recommended daily levels of 10% of total calorie intake coming from protein (17) — leads to protection from diabetes, cancer and extends lifespan (5-8).

Lower levels of thyroid hormones have also been found in people with exceptional longevity: lower fT3, lower T4 and high-normal TSH can be exceptionally long lived. (9,10). Higher HDL is protective; as well as lower levels of LDL cholesterol and triglycerides. (11). Table 1 and 2 shows the Wisconsin and NIA monkeys failed to display the changes that are a typical with CR. In the Baltimore longitudinal study of Aging, men with lower insulin, lower body temperature and high DHEA were found to be longer lived. Humans who voluntarily do CR (myself included) do display these changes with the exception of changes in T4 and TSH thyroid hormones which is mixed in humans.

Overall, humans seem to be responding more favourably to calorie restriction and more closely matches the phenotype displayed mice and rats that have a dramatically extended lifespan. I believe in order to understand the relevance to studies on ageing, we must first understand if the study group actually responding properly to CR, like rodents and humans do.

A little extra weight is not good for you; dispelling the ‘myth’ that being overweight reduces the risk of mortality: Several reports have come out in the last few years suggesting that being overweight decreases mortality. They typically either show a J-curve or a U-curve for BMI, which basically meant that being thin was associated with greater mortality, and being obese is even worse; but being slightly overweight was  actually good for you. (12). They came to this conclusion by looking at a large number of people and excluding all obvious causes of being thin: smoking, alcohol abuse, and pre-existing diseases were controlled for to see what is the optimal BMI in humans. Unfortunately these studies fail because of serious methodological flaws and the inability to control for leanness because of healthy lifestyle, rather than poor diet and ill health.

Healthy individuals eating a diet that is rich in vegetables, fruits, nuts, seeds, and fish are likely to represent a very small fraction of lean individuals. Indeed, one study that was conducted by Cardiff university found that only 15 men out of  2,235 men ate more than 5 fruits and vegetables a day. Less than 1% followed all 5 healthy behaviours.  Following a ‘healthy lifestyle’ is not common here in the UK (13). This indicates that being thin in the general population is more likely to be a result of poor lifestyle choices  and/or underlying diseases than to a healthy lifestyle — which in many studies has been correlated with lower rates of mortality. In fact, just recently it was reported that eating 7 more more fruits and vegetables a day is associated with a 42% reduction in mortality. And the more fruits and vegetables consumed, the lower the BMI. (14).

If we agree that this study does not represent a true ‘anti-ageing’ study because the CR group were not restricted enough to elicit many of the CR responses that drives its ‘anti-ageing’ effect; and that the controls were also overfed, then this study represents what the general population could expect if they were to reduce their calories a little and maintained a healthy body weight.

Both the Wisconsin and the NIA primate studies show that lowering body weight is very important to health and lifespan. And whether or not there is diminishing returns in the effect CR has on lifespan as body weight is progressively decreased, there should be no doubt that excess body weight is bad news when it comes to diseases of ageing such as diabetes, cardiovascular disease, and cancer. These are some of the biggest killers in western countries today.

These studies show that changing dietary habits can have a dramatic impact on your disease risk, and that you have more control than you might think. You are not destined to develop the same diseases as your family and friends if you act now to live a healthier lifestyle. As this study shows, you could potentially add years to your life. And you’ll see the effect on quality of diet plus staying lean is even greater still!

NIA RHESUS MONKEY CALORIE RESTRICTION STUDY

Calorie restriction in rhesus monkeys NIA

In this study they had two groups on the diet to establish what effects CR has on health in young animals and old old animals. The study conducted at NIA was more in-line with rodent experiments where control group were restricted by 10% to avoid the effects of obesity, whilst the CR group are restricted by 30%.

Energy intakes were calculated from tables of energy intake requirements for the rhesus monkeys by age, weight, and gender. Both groups received a relatively healthy diet that was also supplemented with 40% extra vitamins and minerals to insure that the calorie restriction group met the recommended daily intake for all nutrients. However, as the control group also received the same diet, this meant they were super-supplemented. The NIA-1-87 formulation.

The diet is also natural based and contains many phytochemicals and other micronutrients that are beneficial to health and could in synergy with CR to improve health. During the course of the study, measurements were made to see what effects CR had on the monkeys health.

table2

Young-onset: In the CR’d male monkeys there was no effect on glucose levels compared with the controls. In the females there was only a very slight reduction. Triglycerides tended to increase with age across all groups; interestingly, young-onset CR’d females experienced a significant increase in triglyceride levels compared to the control female group (15), which is bizarre, because in humans, there are no differences by gender in the response to CR when it comes to the dramatic lowering of triglycerides.

The monkeys also failed to exhibit several other distinct changes that usually occur with CR: There was no reduction in testosterone or estrogen as we see in rodents and humans. And no increase in the stress hormone cortisol. Serum triiodothyronine (T3) was reduced by 14% in the young and old CR’d female monkeys and very little effect in males. In humans practicing vigorous CR there is a major reduction in T3; but this was not observed when  overweight people who had lost weight to get within the healthy BMI range like those in the CALERIE study (more on that later).

Old-onset: In males there was a significant decrease in cholesterol in the CR’d group. Glucose was also reduced significantly, while there was only a modest effect was seen in CR’d females. Triglycerides were significantly reduced in CR males, and modestly reduced in CR females. (15). Blood pressure was not affected in the monkeys; which is inconsistent with the data in humans, as we see a dramatic decrease in blood pressure from average values for their respective ages to levels that of a child: approx 100/60. (16) Indicating once again that humans respond better than monkeys to CR.

CR has a dramatic effect on cancer if started young: It’s worth noting that one significant effect has been found in the young-onset monkeys: so far none of the calorie restricted monkeys have developed cancer (CR 0/40 vs  6/64 AL) Calorie restriction initiated early in life is powerful in protecting against cancer in rhesus monkeys and possibly humans. This is one effect that is consistent with what we see in rodents. Unlike old-onset rhesus monkeys, the young-onset do see reductions in IGF-1 levels, which may partly explain this effect (although not entirely). In humans pracitcing vigorous CR with protein restriction (10% of calories), both young and old see significant reductions in IGF-1. (17).

Longest lived rhesus monkeys on record: Although survival was the same for both groups in the old-onset group (35.4 years), this was significantly longer than previous reported median lifespan of just 27 years for a rhesus monkey in captivity. (15). Not only that, of the 20 male monkeys in the old-onset group, 4 monkeys in the calorie restricted group have lived beyond 40 years and only 1 control monkey. 40 years is considered the maximum lifespan for a rhesus monkey. Researchers analysed data on lifespan of 3264 rhesus monkeys, and only two 40-year old monkeys has ever been documented.

According to researchers, one year for a monkey is roughly equivalent to 3 human years. (1). So 35.4 years for a rhesus monkey would correspond to about 106 human years? Rhesus monkeys in this study in both old-onset group gained 8 years extra life; equivalent to 24 human years. As the study is still about 10 years away from being completed, I would expect that we could see a few more 40-year old monkeys in the young-onset group.

Calorie restriction slows aging in rhesus monkeys

The NIA group had fairly significant survival advantage over all groups in the WNPRC study. With a 10% restricted healthy diet, the NIA cohort broke longevity records. Is it possible that the 10% reduction in calories with a very healthy diet that was rich in vitamins, minerals, phytochemicals, omega-3 fatty acids was additive in its effects with CR, so that the 10% CR group effectively got the same benefit as the 30% restricted group? As these monkeys have lived far beyond what is typical for a rhesus monkey, it’s clear that quality of diet matters a lot; and being lean is very beneficial for health and longevity.

In studies on rodents, 10% CR can effectively extend lifespan as much as 30%; but this is not true of all strains. In most, the lifespan gained is in proportion to the degree of restriction and the length of time the animal has been restricted.

Translation of ‘moneys years’ to ‘humans years’ might not be exact; it’s just a rough estimate.

CALORIE RESTRICTION DIET IN HUMANS

At least 18 people practicing calorie restriction with optimal nutrition have been studied by Dr Luigi Fontana at Washington University in St Louis. In a study published in 2004, medical records were collected of the participants previous health data which included things such as: body weight, blood pressure, glucose, cholesterol etc to see what effect years of calorie restriction has had on health. Those doing calorie restriction were very lean with a BMI of 19.6 ± 1.9  vs  25. ± 3.2 kg/m2  for the western diet group. Average time on CR was 6 years ± 3 (range 3 to 15 years).

Just recently participants from the CR society had their muscle biopsied and analysed to look at gene expression profiles compared to that of 30 year old controls and age-matched controls (58 years); and also they compared the molecular changes in rats on 40% CR. They hypothesised that CR in humans would have induced a down-regulation of the Insulin/IGF-1/FOXO pathway which has been linked with longevity in animals and humans (20-22). What they found was a very significant down-regulation of the Insulin/IGF-1/FOXO pathway at the transcriptional and post-transcriptional level. The key changes in skeletal muscle gene expression profile that are observed in long-lived rats are also observed in humans.

So not only are humans responding at a physiological level to CR as animals do; but the molecular adaptations seem to mirror that of mice and rats. They also looked at SIRT 1 and AMPK: these two energy-sensing pathways were significantly up-regulated in people on CR. FOXO3A and FOXO-4 were significantly up-regulated: these are known to modify many ‘longevity genes’ in animals and increase activities such as DNA repair, antioxidant defenses, immunity, protein turn over, and cell death genes. (22). Autophagy, which helps remove dysfunctional cell components to recycle was also significantly up-regulated by CR.

Looking at (Figure 1b (23)), it looks as if people on CR had more similar gene expression profiles to the younger individuals in the study. The ‘gene expression’ of people on CR is more like that of a 30 year old than the age-matched 58-year old control group. This is a very important finding to see if the same response to CR is conserved across species to humans.The study found that major risk factors for cardiovascular disease were reduced significantly in people on CR. The average Total cholesterol and LDL-C concentration for the CR group was in the lowest 10% for people in their age group (50 years). Also, even more dramatic, the levels of triglycerides in the CR group were lower than 95% of Americans who are in their 20s. And their HDL (good cholesterol) was higher than 85-90% of people in middle age.

Fasting insulin was 65% lower than the western diet group and glucose was also significantly lower too. People on CR have also been found to have lower body temperature, lower thyroid hormone T3 as well, but people who exercise vigorously and maintained a similar BMI did not see these reductions. (29,31)  Participants of the study also had extremely low blood pressure, equivalent to that of a 10-year old. They had almost non-detectable or very low levels of inflammation measured by c-reactive protein. The IMT carotid artery thickness was measured and found to be 40% less in the CR group compared with the controls: 0.5 ± 0.1 mm in the CR and 0.8 ± 0.1 mm for controls. None of those eating a CR diet had any evidence of atherosclerotic plaque.

To show the powerful effect  that CR had on their health, the researchers were able to gather medical records from 12 of the individuals in the CR group and show that just like the western diet group, values for the CR group were average (50th percentile) before embarking on the diet. Possibly even more impressive was results showing that CR in humans might possibly slow down aging of the heart itself. They looked at the diastolic function of the heart and its ability to relax and fill the left ventricle, and found that people on CR had hearts that were similar to those who were 15 years younger.(17). And those on the diet also had the heart rate variability of a person 20 years younger. (18)  It looks as if CR must have had a rejuvenating effect on heart function and wasn’t just merely slowing its decline in function and performance.

WIll calorie restriction work in humans?

Looking at the data we have thus far from mice, rats, rhesus monkeys, and humans, we are able to make comparisons to see the differences between each species in how they react at a molecular level and at the physiological level to CR; and also how they react to the various degrees of calorie restriction. It’s clear that people on a calorie restriction diet do display a more CR-like state than either the NIA or Wisconsin rhesus monkey studies.

Not only that, people in the CALERIE study who were overweight and merely reduced their body weight to a ‘healthy’ weight from a BMI of 27 to 24 with 25% CR, never exhibited several CR signatures, nor did they have as significant reductions or changes in total cholesterol, LDL-cholesterol, triglycerides, inflammation, thyroid hormone levels, testosterone, estrogen, IGF-1 and cortisol.(26-28).  All of these are strongly influenced in people studied at WUSTL who are from the CR Society and practice moderate-severe CR. (16-19, 23). Many of these signatures that were not observed in the CALERIE study were also either not observed in the CR primate studies, very inconsistent, or modest in their change or effect. (25-28). This indicates that the level of CR in the primate studies, as well as the CALERIE human study were insufficient to elicit the key changes that are responsible for the age-retarding effect of CR.

Apart from the CR being insufficient to elicit these changes, another possibility could be that the declining difference between energy intakes of the NIA rhesus monkeys (20% less than ad lib for males and only 12% for females) could be the reason why little differences were seen. It was reported also that the calorie restricted monkeys did not exhibit much sign of hunger during the study either; another argument pointing to the fact that the CR group needed to be restricted further.

Before embarking on this very long study, it may have been wise to restrict monkeys to various degrees to see if there is a ‘cut-off point’ to where CR does not improve their health further. If they display the CR-phenotype in a more consistent and powerful way, then establish this level of restriction for the CR group for a lifespan study, as long as the level of restriction was not inhmane and the animals did not display poor health from it.

Fortunately we have a lot more control over our own diets, exercise and supplements than animals who are subjected to these diets. The interactions between all of these are only just now being discovered. It’s only a matter of time before we’ll have reliable markers of ageing which we can use to see if our diets are working. In response to the results we see with the diet, we are able to change accordingly to get into the most optimal and CR’d-like to have the best chance for living longer and healthier lives.

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24. Luigi Fontana, Samuel Klein, John O. Holloszy, and Bhartur N. Premachandra
Effect of Long-Term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones
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Canto and Owen – Two Rhesus Monkeys on CR

Below are some high resolution pictures of two rhesus monkeys around the same age, Owen is a couple years older than canto. Canto is 27 years of age right now and still looks like a youthful rhesus monkey. This is achieved by a reduction in calories alone.

I expect people who start CR at an early age, they could look extremely youthful in middle age and beyond.

People always think I am younger than my age — usually people guess around 16-17 years old. I am actually only 3 months away from being 25!  I guess the difference can only grow over time. Is it possible to look only 25 at 50 years of age??? Maybe that might be pushing it, but it will be an interesting to see.


CLICK ON PICTURES FOR BETTER DETAIL

NORMAL DIET

CALORIE RESTRICTION DIET


Comments on the Rhesus Monkey study

Comments on the Rhesus Monkey study

CALORIE RESTRICTION REALLY DOES WORK IN MONKEYS

Over the past few days I’ve been looking around on the internet, checking out the CR Society email lists and the talk among the life extension community to see what others think of the study and whether or not this does really support calorie restriction working in non human primates and possibly humans. First lets look at the survival curve for overall mortality and non age related mortality. First if you haven’t read the first post I did on this, scroll down to check it out first.


As you can see there is a big difference in survival in survival curve which excludes deaths from certain causes that are thought not to be caused by diseases and aging. Seven of the control Monkeys and Nine CR Monkeys died of non–age-related causes, which included complications of anesthesia, gastric bloat, endometriosis, and injury.

Anesthesia – The monkeys every year go through a cycle of tests, in order to perform some of these the monkeys have to be sedated. Sometimes even if the monkey was otherwise healthy, things can go wrong. The question is what has this got to do with aging, and should it be included when looking at the life extending effect of Calorie Restriction. Since the monkeys I believe are put under anesthesia quite frequently, possibly at least once a year (although I need to check on this to make sure) then there can be a risk when doing this. But if a monkey dies from anesthesia it tells us absolutely nothing about whether the animals aging was being slowed down or not by calorie restriction. Most humans do not go under anesthesia once or twice a year to have extensive medical tests done on them, in humans more care is probably taken as well in order not to kill the patient. If however there was a trend that as the monkeys aged they were more suceptible to death from anesthesia then I could understand including it in the age related mortality survival. Also taking into account any chronic diseases the subject might have had prior to going under anesthesia. The fact is these deaths could have been very well preventable. The researchers also never noted any increased risk of anesthesia deaths for the calorie restricted monkeys.

Injury – Accidents cannot be totally prevented. If someone fell and suffered severe head trauma, does this again tell you anything about whether or not calorie restriction has slowed down (or not) aging? Clearly the answer is no. One can possibly argue that the rhesus monkey might have been weak from aging and fell. But we don’t know the details of how the injury occured, so we can only speculate. However the fact is accidents happen to ‘anyone’ and they do not tell you anything about aging other than when we see increase risk of falls from elderly humans which result in hip fracture and death. Should injuries be exlcuded? Absolutely! I have yet to see a good argument why they shouldn’t.

Gastric bloat – I do not know how many monkey died from this but again this is a totally preventable death! From an article published in 2002 in the Wall Street Journal when refering the survival of the monkeys;

“Those figures exlcude monkeys whose deaths wree deemed accidental, such as when a batch of overcooked food caused a fatal stomach ailment called gastric bloat”

This is something that can happen at absolutely any age and should have been prevented, there is no reason at all to include it in the survival curve, and once again does not show whether or not CR was working. It was simply a preventable accident that can happen to any healthy monkey, both CR’d and Ad lib.

These are all deaths which I am very comfortable with the researchers excluding from their survival stats. They really do not tell us anything about aging and can happen at any age, and they were not increasing in frequency with age. In fact quite a few of the deaths seemed to be in the early stages of the study and later on the carers were better able to prevent more deaths from the causes above. In time I suspect that the overall mortality curve will show statistical significance. As there are three groups in the study we cannot tell what the average lifespan of the calorie restricted and ad lib groups are, but this data should be in quite soon. All animals are now apparently 27 years of age which is about the lifespan for a rhesus monkey, with the maximum being 40 years. So we could be waiting quite a while yet if a few of the monkeys reach 40 and beyond. So far almost all of the control monkeys have age related conditions that could eventually result in death, whereas in the CR animals a large percentage of them are in good health. As you can see below, througout the course of the study the control animals are experiencing more cancer, more cardiovascular disease, and big problems regulating glucose. Monkeys are particularly suceptible to age related diabetes than humans are, but calorie restriction seems to completely prevent this and even in two of the rhesus monkeys it reversed pre diabetes stage when they entered the study.

This tells us one important thing that all of us wish to have, a good quality of life. When on CR we are likely to spend more years with good health and then less time with ill health before death. It’s not uncommon that people today spend decades with chronic health conditions that could be almost completely preventable. There has been some commentary about this study on the CR lists, this was one interesting point.

Michael Rae says; “This is the best of the 3 nonhuman primate studies, and still has some flaws: the actual differnce in Calorie intake has dwindled down to almost zero, because none of the animals are very engaged with their rather monotonous and restricted lives; the food isn’t the best; there were definitely nutritional problems (such as excessive retinol, early on) in the diets; we don’t *really* know how how to best care for and feed nonhuman primates, nor how long they can live in captivity, because so few have been studied; and above all, there’s evidence that the AL group probably should’ve been restricted a bit more and the CRed animals restricted even further in turn (no effects on menstruation in the females, and probably some of the AL diabetes is related to modest overweight).”

Researchers are usually careful to make sure that the control group are normal weight and not affected by issues largely releated to being overweight. So animals are usually restricted by 20% from their true ad lib intake to avoid these complications. Michael is saying that the both groups should have been restricted more. I do believe the researchers found problems with restricting calories more severily in the CR group, they were deemed to be too thin and possibly pose future health problems which might cause issues further on in the study. I think the researchers were right to er on the side of caution here because the last thing we want is a complete failure because of health complications. There might have been none and most of the monkeys apparently were fine but like other studies in dogs, they increased the calories of some of the rhesus monkeys. I’m unsure if the information about there not being a difference between the both groups in terms of calorie intake, I heard this was an issue at the NIH study but not wisconsin. Maybe Michael has communicated with the researchers at Wisconsin or other people who knows about the situation there. And finally the food the monkeys are given, they are given monkey chow which is not the best food but it would be extremely difficult to give them anything else. With humans we can control our own diets, it’s quite easy, and we know more in terms of what we need to stay healthy.

If anything the humans will respond even better. We have good access to health care (although the monkeys did recieve good health care also), we are not stuck in cages all our lives which would surely leave all of us quite depressed. The human data is pretty strong, even taken at face value and not comparing to the control groups, it’s still very impressive. Almost every marker of health is improved by CR. Maybe now people should stop using the saying “It doesn’t make you live longer, it just seems like it”. Because this is not true 🙂

Calorie Restriction is still the best way we can extend our lives, it’s the best way to reach 100 and beyond, and it’s the best way to ensure that you reach the point when medicine has advanced enough to slow and reverse aging.

If anyone has any good objections and why they should include the deaths I mention above, I’d love to hear it. So far there has been no good reasons why they have any indication or not whether CR is working.

EDITED: 13:30 15/07/2009 —


IN RESPONSE TO JUNK FOOD SCIENCE BLOG

Responding to some things from JunkFoodScience where I seen that there were many mistakes and misleading words.

Sandy Szwarc says;

“The non-aging-related causes of death included monkeys who died while taking blood samples under anesthesia, from injuries or from infections, such as gastritis and endometriosis.”

The monkeys did not die from infections or gastritis. They mostly died for prentable causes and more care should have been taken i.e Not overcooking batch of food and killing the monkeys with gastric bloat. Anesthesia and injuries I already explained.

Sandy Szwarc says;

“As the supplemental data explains, 16 deaths from “non-age-associated causes were censored and their age of death used as the time variable in the regression”

She words it so the average reader without looking more into it would probably assume these 16 deaths or much more of them were all from the CR group. When is was 9 deaths for CR and 7 for ad lib.

Sandy Szwarc says

“but they could realistically be adverse effects of prolonged calorie restrictions on the animals’ health, their immune system, ability to handle stress, physical agility, cognition or behavior.”

Well no there is no data that supports immune systems were weakened in monkeys and actually there is evidence monkeys have better immune systems under CR. They never died from infections in the study. The CR animals usually are able to withstand greater stress as seen in other lab animals, the CR monkeys were reported to be in better shape physically, as you can see by their posture and the way they move on videos. And in terms of cognition, it seems the CR monkeys are doing better from an earlier paper which showed better cognitive skills and problem solving. Not much behaviour differences were noted in the papers on the primates.

Then she makes this claim

“the control animals were overfed 20% more than their usual diet, while the CR monkeys’ diets were adjusted to keep them about 30% less than the control monkeys.”

The control group were not as I recall fed 20% more than their ad lib intake, and they also had their food taken away from them also after the period of feeding time was over. She doesn’t supply any references to support what shes saying. Then she assumes that the CR monkeys were fed 10% less to achieve a 30% reduction [after the 20% increase in control group] in calories? No, each CR monkey had its baseline intake calculated and reduced by 10% each month until reaching 30% below its normal calorie intake. The ad lib calorie intake was not increased by 20% to achieve this 30% reduction. The Ad lib monkeys were not true eat your brains out ad lib group, this was done at a previous study in Maryland where the control grop only reached 25 and CR group 32, but the ad lib intake in this study was also somewhat restricted to prevent obesity. Although it might have needed to be restricted a bit more and the CR group more also. All animals have a feeding period of about 8 hours, and food is removed from both groups and counted. So two differences in the Rhesus monkey studies. The NIA study reduced calorie intake from tables of how much each monkey should each should eat for their age and body weight, and the Wisconsin study reduced CR animals by 30% from their baseline intake after recording it for 3 – 6 months before starting the 10% reduction in calories every month for 3 months until reaching 30% restriction.

This presentation about the study shows that the female restricted group are now around 20% restricted comapred to the control group, whereas by their own baseline intake they at are 30% fewer calories. The males are able to stay around 30% restriction over time. This is the food intake for CR and Control group, they have their food measured everyday.

Some final thoughts

Now a suggestion to everyone. When reading blogs around the internet please try to be aware of false information, do a bit of research into it yourself. Many people have their own agenda usually don’t actually read into the science properly, and they try to use clever words and twist stories around. Sometimes the mistake is genuine, but bottom line is look into yourself if you’re not convinced. As for the JunkFoodScience blog, there were many obvious mistakes even after my first quick read through. Unfortunately for the average person reading they might easily be persuaded by people like her. My job here is to try and give you the latest information and media on CR, trying to be as honest as I can, and report the latest studies on health and try to give the correct data and not ‘twist’ stories around.

Thanks to a comment I recieved earlier you can read about Ms. Szwarc HERE . From looking at her funding sources, like McDonalds, she isn’t exactly the kind of person you wan to listen to. She defends obesity, junk food, she claims obesity makes you healthier and a bunch of other crap. She is quite a good writer and can easily convince some people, don’t be one of them. Also check another post about Szware HERE .

Calorie Restriction Extends Lifespan in Monkeys

CALORIE RESTRICTION WORKS IN MONKEYS

Just before I left for work earlier today I had a google alert that read something like “Calorie Restriction extends lifespan in Primates”. Well not much of a surprise, but happy to read the paper when I can. The article I first looked at was from wired.com. Here is what they said;

“Up until now, all the clear-cut evidence that caloric restriction slows aging has come from lower organisms,” said John Holloszy, a Washington University gerontologist who studies caloric restriction in people and was not involved in the current monkey study. “This is the first study to show that caloric restriction slows aging in a primate species. And of course, we’re primates, too. It’s a lot more relevant to humans than the mouse.”

Click image to enlarge (best quality pic of Canto and Owen)

“All the surviving monkeys are now at least 27 years old, the rhesus equivalent of old age. Those fed a calorically restricted diet have dramatically lower levels of cancer, diabetes, heart disease, brain atrophy and lean muscle loss. Just five of the 38 restricted monkeys have died from age-related causes, compared to 14 of 38 in the control group.”

Click image to enlarge
The CR monkeys seem to be looking youger and also keeping a nice fur coat as is quite clear in this picture

Does this make you more confident that CR will work in humans? For me the answer is yes. They visually looking younger, they’re also showing big differences in survival.

Source; WIRED

Calorie Restriction Protects rhesus monkeys from sarcopenia

Well according to that abstract it significantly slows the decline. We see the same with various hormones, and bone with CR too. Start off at a lower level, but the decline is much slower.

There was an interesting study a little while back on rodents. An article states;

“Scientists from the University of Calgary found that rats fed a nutritious, calorie-restricted diet maintained their muscle mass much better than rats that ate a normal amount of food. “It’s the equivalent of an 80-year-old rat with the muscles of a 20-year-old rat,” said Russ Hepple, a physiologist at the University of Calgary.”

It seems very likely the same effect will be seen in humans. The fact that CR preserves muscle mass is very nice because not only could we expect to be more functional with age, but also have much less chance of bone fracture.

People with better muscle function and mass tend not to be as susceptible to falls as old frail people with poor muscle function, coordination…

Even at 18y the CR group had a higher ESM than the ad lib group at 10 years!

Heres a direct link to the graph from the paper

Attenuation of sarcopenia by dietary restriction in rhesus monkeys.
Colman RJ, Beasley TM, Allison DB, Weindruch R.

Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Ct., Madison, WI 53715. rcolman@primate.wisc.edu.

Sarcopenia, the loss of muscle mass with normal aging, devastates quality of life-and related healthcare expenditures are enormous. The prevention or attenuation of sarcopenia would be an important medical advance. Dietary restriction (DR) is the only dietary intervention that consistently extends median and maximum life span, as well as health span in rodents. Evidence suggests that DR will have a similar effect in primates. Furthermore, DR opposes sarcopenia in rodents. We tested the hypothesis that DR will reduce age-related sarcopenia in a nonhuman primate. Thirty adult male rhesus monkeys, half fed a normal calorie intake and half reduced by 30% in caloric intake, were examined over 17 years for changes in dual-energy X-ray absorptiometry-estimated skeletal muscle mass. Body weight-adjusted skeletal muscle mass declined somewhat in both groups but was far more rapid in the control group. We have shown that moderate, adult-onset DR can attenuate sarcopenia in a nonhuman primate model.

PMID: 18559628 [PubMed – in process]

See related articles:

Benefits of CR