The Mega Foundation

Questions Concerning Caloric Restriction

July 24, 2004

(1)  What fraction of the protein and fat we consume isn't burned as fuel in the mitochondria, but is employed for turnover of protein and fats in the body? For example, consider a woman who ingests 2,200 kilo-calories on an ad lib diet, of which 200 kilo-calories (40 grams of protein and 4.5 grams of fat) are used structurally rather than metabolized as fuel. Now consider the same woman 50% calorie-restricted, who requires 300 kilo-calories in protein and fat (viz., 58 grams of protein and 7 grams of fat) for structural maintenance. She's functioning on 1,100 kilo-calories of which only 800 calories are oxidized for energy. Consequently, in metabolic terms, she's actually 60% caloric-restricted: (2,000 - 800)/2,000.

(2)  One of the issues that I want to address before it becomes accepted because no one has questioned it is the idea that CR doesn't actually exist as a phenomenon... that it's all just a matter of size and the corresponding calorie requirement (Scott McClatchey) My picture of Scott McClatchey's model is that there's no such thing as a CR effect, and there's no such thing as metabolic efficiency. Everybody's metabolic efficiency is about the same. A woman who is 4' 10"' tall, with a BMI of 20.1 who weighs 95 pounds will, in accordance with the Harris-Benedict estimation formula, require in the neighborhood of 1,579 calories a day, assuming an activity factor of 1.35. Harris-Benedict_Equation.htm There might be modest variations in this woman's caloric requirements depending upon her percentages of fat, bone mass, etc., and of course, there will be significant variations with levels of exercise, but basically, all 4' 10" women who engage in the same level of exercise will require the same number of daily calories. At the other extreme, a 6' 8" Goliath with a BMI of 25 will weigh 228 pounds, and will require about 3,218 calories a day to keep him percolating. Using the conversion factor that Scott McClatchey provides, that a 21% reduction in calorie intake will result in a 13% increase in lifespan, then our 50%-calorie-restricted "Davida's" average lifespan will be 50% times 13/21, or 31% longer than Goliath's. If I set the average lifespan of the "Little Woman" at 82, Goliath's average lifespan would be about 55 (assuming that he doesn't smoke). If I set the maximum lifespan (defined as the mean lifespan of the longest-lived decile, or roughly, the lifespan at which 95% of the population has already died) at 23% above the average lifespan, then our longest-lived one-in-twentieth Goliath would have a maximum lifespan of about 67, and our Davida would have a one-in-twenty lifespan of about 100. (Only about one person in 10,000 makes it to 100.) More about this later. If I use a lower maximum lifespan of 96 for our  "Little Woman", then I find Goliath having an average lifespan of about 52,and a maximum lifespan of 64, requiring reading glasses at, perhaps, 30. If in addition, he burns extra calories through exercise... if, for example, he's very muscular, and works on a construction crew... then he might require reading glasses when he's in his late 20''s, and would be physiologically 65 at 40.

Subject BMI Weight Calories Cal./2,200 Relative Age Avg. Max
4' 10" "Davida" 20 95 1,579 0.7177 1.175 82 100
5' 4" Man 23 134 1,984 0.9018 1.061 74 90
5' 8" Man 23 151 2,199 1.0000 1.000 70 85
6' Man 23 170 2,427 1.1032 0.936 65 80
6' 8" Man 25 228 3,068 1.3945 0.786 55 67



(3)  What happens with people who can eat and eat and eat and not put on weight? (Are there such people? I think I was one of them until I reached my late 20's.) Do they actually eat much less over the course of a day's time than they seem to be eating? Or do they simply not absorb more food than they need? Or do they absorb it into their bloodstreams, but then get rid of it without storing it as fat? Or are they metabolically inefficient, perhaps generating extra heat with their extra calories? Or several of the above?

(4)  For people who have adapted to the temperate and arctic zones (e. g., us), the ability to store fat to last through long hard winters would have great survival value. For people who have adapted to the tropics, this shouldn't be so necessary.
    This raises questions about Aubrey de Grey's argument that the CR effect need only be sufficient to last through a winter or two. In the tropics, that requirement for a CR effect more-or-les wouldn't exist. For that reason, it becomes especially important that caloric-restricted monkeys show extended lifespans, since monkeys are tropically-adapted animals found outside the tropics only in zoos. That seasonal requirement for a CR effect also shouldn't exist for very dark-skinned people who have also adapted to tropical milieus.
    Personally, I think that the results of the Washington University study, coupled with the marked depressions of body temperature that we're experiencing (including my own temperatures in the mid-90's), argue that a caloric restriction effect is occurring in us humans. Whether it's good for two years or twenty eamins to be proven, but the answers to some of these answerable questions should help us find out.

(5)  How do fully fed people with BMI's in the range of 18-20 compare with the CRONers in the Washington University study when it comes to serum lipids, carotid intima thicknesses, and serum glucose and insulin levels? Do they have the same values? Are these remarkable values simply a matter of being slim? Are they shared by all who are equally slim, or are the CRONers' values unusual? (I suspect the answer is that the CRONers are very unusual. Otherwise, the Washington Universty researchers wouldn't have stated their results the way they did.)

(6)  How much of the CRON results are a consequence of the ON part of the CRON diet? (What I'm seeking here is confirmation that a CR effect is taking place that goes beyond everyone who has a BMI of 18 to 20 and good nutrition.)

(7)  In dealing with rates and percentages, we must be careful to remember that rates and percentages aren't additive. Rates are multiplicative, and percentages must be converted back to ratios and then multiplied. For example, 14% + 14% = 29.96%. (1.14 X 1.14 = 1.2996). This means that a linear relationship between calorie-restriction and lifespan is really pointing to a non-linear relationship between true calorie burn rate and lifespan--not to mention the added complication that not all calories ingested are burned (see paragraph 1 above).

(8)  If aging is a result of burning calories, why isn't lifespan inversely proportional to calories burned? If I burn calories twice as fast, shouldn't I live half as long? If I'm 60% calorie-restricted, shouldn't I live 2 times as long?

(9)  One way I can arrive at a model in which calorie-count isn't inversely proportional to lifespan is to suppose that part of aging depends solely upon the calender and is independent of calorie intake. If I assume that 50% of aging is tied to the calender, and 50% of aging is dependent upon calorie intake, then cutting calories by 50% would yield a rate of aging which is 50% + 50% X 50% = 75%. This would lead to a lifespan extension of about 33%... close to the 31% discussed above. However, I know of no reason why aging should be tied to the calender.