The Mega Foundation
The Lifetime-Energy-Budget Model
April 20, 2004
Assumptions
Fixed lifetime energy budget. (Age is proportional to total calories* burned.)
Minimum daily calorie requirement for weight maintenance (e. g., 1,500 calories for our man, not including exercise).
Excess calories above this 1,500-calorie daily minimum up to a maximum (e. g., 3,000 calories) are burned as excess heat.
Still more calories above this 3,000-calorie "deadband" ceiling are converted to fat and stored away for a rainy day.
* - "Calories"
refers to kilocalories, per common usage.
Lifespan
Lifespan is inversely proportional to the average rate at which calories are burned.
Halving caloric intake from an average of 3,000 calories a day to an average of 1,500 calories a day doubles average lifespan from 80 years* to 160 years, and maximum lifespan from, viz., 110 years to 220 years..A 60% calorie reduction would lead to a 200-year average lifespan and a 275-year lifespan maximum lifespan.
Lifespans fit an accelerating hyperbolic curve (see curve below), increasing 11% with 10% calorie restriction, and rising to a 100% lifespan extension with 50% calorie restriction.
Master athletes (beginning as swim team members in childhood?) burning 6,000 calories a day would age at twice the normal rate, needing reading glasses in their early 20's, and looking like, and suffering from the age-related diseases of the average 80-year-old by the age of 40. Virtually no master athlete burning 6,000 calories a day would survive to the age of 50.
* - I'm assuming that the
average lifespan for our hypothetical male might be 80 years if he were immersed
in the same kind of controlled and protected environment that we provide
for animal models.
Effect of Caloric-Restriction upon Flowering, and Reproduction
None. Calorie restriction merely eliminates the burning of calories as wasted heat.
Effects of Caloric-Restriction upon the Sizes of Growing Children
None.
Genetic Changes with Caloric-Restriction from Birth
All genes that show age-related changes will change proportionately slower with caloric-restriction.
Effect of Caloric-Restriction upon The Shape of the Survival Curve
Same shape as that for the fully fed, except stretched along the abscissa... e. g., 100% for a 50% calorie restriction..
Calorie Restriction Late in Life
Will slow the rate of aging the same amount at any age. How much this extends lifespan will depend upon how many calories have already been burned.
For someone who is already slim, there will be no reversals in aging biomarkers or in aging related genes when calorie restriction occurs. Changes in genes and biomarkers will occur slower than in fully fed individuals.
Calorie Restriction and Weight Loss
There can be no change in aging biomarkers with weight loss.
If there is an improvement in, say, blood pressure, fasting blood sugar, and insulin sensitivity, then these changes must be considered weight-loss-driven, and the so-called "aging biomarkers" must be reconsidered to be not just aging biomarkers, but instead, a function of both aging and weight.
Effects of Antioxidants and Other Biochemical Interventions
Administration of antioxidants, or of antioxidant stimulants should extend the maximum lifespan.
A review of the predictions of this lifetime-energy-budget
model shows that it falls wide of the mark in fitting the experimental
evidence. It's a seductive model. It fits with our intuitive ideas about cars
and other mechanical gadgets... they wear out... but it seems to me to fail to
account for negligibly senescent animals such as the red sea urchin and the
rough-eyed rockfish. In any case, it's at odds with late-in-life gene reversions
when an organism goes on a CRON diet. It's tempting to think of CR in simple
terms of metabolic rates, but that may not be the whole story. ."Selected
Contribution: Long-lived Drosophila melanogaster lines exhibit normal
metabolic rates" and Live
fast, die old - Nature.
So if this isn't a realistic model of caloric-restriction,
what is?
What We Actually Observe with Calorie Restriction
Lifespan vs. Degree of Calorie Restriction
10% caloric restriction yields a 13% lifespan extension ("Beyond the 120-Diet", pg. 49), compared to 11% using a lifetime-energy-budget model..
50% caloric-restriction yields a 42% lifespan extension, compared to 100% using a lifetime-energy-budget model.
Lifespan improvements appear to be increasing at a decreasing rate with increasing calorie restriction. (Graph A on page 48 of "Beyond the 120-Diet" also shows this phenomenon).
Effects of Caloric-Restriction upon the Sizes of Growing Animals
Caloric-restricted animals are stunted and late to mature when calorie-restricted from weaning onward.
Effect of Caloric-Restriction upon Flowering, and Reproduction
Flowering and reproduction are put on hold while an organism is caloric-restricted.
The caloric-restriction response appears to be a "hard-times" survival mechanism, diverting resources from growth and reproduction to repair and preservation of the organism until times improve.
Genetic Changes with Caloric-Restriction from Birth
Some but not all of the genes that show age-related changes will change proportionately slower with caloric-restriction.
Caloric Restriction Later in Life
Caloric restriction when growth is complete (6 months in mice;15-18 years in humans) is as effective in lengthening lifespans as caloric restriction from the time of weaning ("Beyond the 120-Year Diet", pg. 50)
Caloric restriction at 11 months in mice (27-33 in humans) and 18 months in mice (45-54 in humans) is about half as effective as caloric restriction from weaning.
This poses a mystery, since beginning caloric restriction at 6 months (the human equivalent of 15-18) gives the full benefits of caloric restriction from infancy (call it 1 year of age in humans), whereas beginning caloric restriction at 11 months (the equivalent of 27-33) and at 18 months (the human equivalent of 45-54) yield the same 50% in lifespan extension. Why this step-function drop between 6 months (15-18) and 11 months (27-33)? Why is there no difference in survival extension between 11 months (27-33) and 18 months (45-54)? This doesn't compute.
Genetic Changes with Caloric-Restriction Later in Life
Weindruch and Prolla found that caloric restriction slows aging in 84% of the genes that show major changes with aging ("Beyond the 120-Year Diet", pg. 58).
Spindler, et al., found that caloric restriction very late in life produced about 70% of the gene change retardations that occur in mice that have been caloric-restricted since weaning.
This should come as no surprise, since in Biosphere II, six to eight months after beginning CR, the eight staff members show dramatic reversals in various aging biomarkers (pg. 44). Similar changes are observed among those of us who take up CR, presumably at any age. If caloric-restriction merely slows aging from the time it's instituted (as in the lifetime-energy-budget model), then we would expect no changes in the biomarkers of aging when caloric-restriction begins, and only a slowing of aging beyond that point. But if someone who is 80 can return to blood lipid profiles and other aging biomarkers characteristic of a much younger age, it would seem as though their lifespans would be considerably extended. Roy walford says of this (Beyond the 120-Year Diet, pg. 61), "If followed for a long period of time, the CRON diet will retard the rate of aging from whenever in life it is begun---and even rejuvenate the functions of some (not all) of your bodily functions."
It would seem to me that there is something like an age-independent degree of partial rejuvenation. If so, this would extend the franchise to include senior citizens who have the most to gain from the remediation of aging, and who are also best endowed to support aging research. However, how this partial rejuvenation translates into longevity extension is an interesting question.
It might seem at first as though the optimum strategy would be to wait until you're old to embrace caloric-restriction. Why give up pizza before you have to? However, apart from the uncertainties regarding how lifespan extension scales with the age at which caloric-restriction begins, there's also the issue of developing cancer and other debilitating diseases that might be avoided by adopting caloric-restriction early, before the first heart attack or other irreversible trauma occurs. Then, too, would you rather have your age backed up 13 years at 35 or would you rather have your age backed up 13 years at 85?
In
examining this triplet
of curves, it's interesting to note that the rightmost curve, denoting
lifelong caloric-restriction, appears to be stretched out along the abscissa,
whereas the middle curve, representing starting CR at the beginning of old age,
has almost the same shape as the control group except that it's shifted to the
right.
| Home |