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 .