Last Night's Chart Re-Examined

April 22, 2004

An examination of yesterday's chart, combined with prior data in my possession, reveals some interesting insights.
What I'm going to try to adduce from this chart is very, very tenuous because I'm trying to interpret a chart with a straight-edge and an eyeball. (I'm assuming that the chart is computer-generated from a smoothed table of experimental data, since the alternative is to suppose that someone generated the chart with a set of French curves as an objet d'art. Of course, if I'm wrong, and the curves aren't meaningful... well, I guess we'll just have to call the whole thing off. But hopefully, that isn't the case.)
A Fully Fed Population
The y-axis in this chart gives the percentage of mice still alive.
The "Begin CR at start of OLD AGE" arrow at the bottom of the chart is said to represent 60 to 65 years of age in human terms.
The 25% Mortality Level in a Fully Fed Population
The 75th percentile on the survival curve for the normal mice, when 25% of these mighty mice have died, looks as though it corresponds to a human age of about 82 to 89 years of age. This amounts to 22 to 24 additional years of life for an equivalent human population.
The 50% Mortality Level in a Fully Fed Population
The mid-point on the left-hand curve, where half of the normal mice have died, corresponds to a human age of 97 to 105, giving the average human 37 to 40 more years to live
The 95% Mortality Level in a Fully Fed Population
The "prior data in my possession" gives the date of the last normally fed mouse's death (where the left-hand curve drops to zero) as equal, in human terms, to 119 to 129, affording the longest-lived equivalent human 59 to 64 remaining years to live. (These have to be Methuselah mice!)
A Caloric-Restricted (CR) Population
Now look at the red curve... the survival curve for the mice that have gone on 44% caloric-restriction at the human equivalent of 60 to 65.
The 25% Mortality Level in a Population 44% Caloric-Restricted Beginning at Age 60 to 65
At the 75th percentile, the caloric-restricted mice appear to have experienced a lifespan extension almost as great as those at the 50th percentile. If I estimate it at 4/5ths that of the 50th %-tile human lifespan extension of 16 to 17 years, I get a human-equivalent lifespan extension of about 13 to 14 years, and a lifespan percentage increase at least 60% greater than the remaining lifespan for the normally fed population. The equivalent humans would live to be 95 to 103.
The 50% Mortality Level in a Population 44% Caloric-Restricted Beginning at Age 60 to 65
At the 50th %-tile, I know that the lifespan extension for the average member of the population, if caloric-restricted, will be 16 to 17 years, as mentioned above. That would bring the lifespan of the average person, if caloric-restricted at 60 to 65, to 113 to 120.
The 95% Mortality Level in a Population 44% Caloric-Restricted Beginning at Age 60 to 65
The age of the middle of the longest-lived decile among humans who are 44% caloric-restricted at the age of 50 to 65 would be 19 to 21 years later than they would if the hadn't been caloric-restricted. Adding 19 and 21, respectively, to 119 and 129 yields ages at death of 138 and 150.
What This Might Mean
What's important about this is that it looks to me as though there's constant offset of, perhaps, 13 to 14 years, combined with a variable term that's proportional to the time spent on CR.
This 13-year "rejuvenation" fits in with what I had derived earlier for the degree of rejuvenation corresponding to a 3.1-fold reduction in mortality when Dr. Spindler's mice were caloric-restricted "at the beginning of old age", but of course, both of my assessments are on very shaky ground, and for now, I guess, are SWAGs.
Of course, this is crude indeed, but looking at the chart, I'm speculating that the greater part of the lifespan extension brought on by late-in-life caloric restriction consists of a constant displacement in the neighborhood of 12-to 14 years. This would seem to be consistent with the dramatic improvements in every CR practitioner's aging biomarkers that occur within months after the induction of caloric-restriction.

I'm excited by the fact that most of the beneficial effects of caloric restriction seem to come on within months of the initiation of caloric restriction (or of just plain weight loss). This means that experimental regimens can be evaluated in humans within a short time. The question of whether CR works to sizably extend human lifespans can be belabored by the Doubting Thomases for the next couple of decades, but from a pragmatic viewpoint, I think it's history. The point is that CR hugely improves cardiovascular and glucose management parameters, and, I should think, CR no longer needs to be justified on the basis of proven "youth extension". The health benefits alone should pay its freight.
One point I'd like to make is that, at least in my own case, CR has been so easy, comfortable, and natural that I have no need to eat the way I did before I began this Odyssey last summer. (I have to tell you, though, that yesterday, we visited the Jack Daniels Visitors Center in Lynchburg, Tennessee, and sitting in the cane-thatched rockers on the front porch of the Visitors Center, my bony bottom made its presence known. But oh well. It's all in a good cause.)
Anyway, to get to the questions:

• How do such aging biomarkers as total cholesterol, HDL, LDL, triglycerides, blood pressure, and fasting glucose levels vary as a function of BMI (Body Mass Index)? Where do they fall among individuals who can't put on weight on a bet (like the fellow yesterday who said he couldn't put on weight if he swallowed buckshot). These folk can, and often do, eat everything that doesn't get out of the way, and yet, they don't add a pound. (I was that way until I reached my late twenties.) How do their aging biomarkers compare with those of CR practitioners who present the same BMI values.
Presumably, the slim and trim ad libitum eaters don't fare as well as those who practice CR, but the leaner you are, this side of starvation, the longer you live. I suppose blood pressures are lower than they are among the overweight, and there isn't the added burden of carrying around, and nourishing gallons of fat.
Knowing that might allow the teasing apart of the relationship between weight loss and the effects that are uniquely attributable to CR.

• What's the month-by-month time profile of CR changes? (Exact numbers probably aren't in the cards, but a controlled experiment involving a relatively homogeneous population losing weight in a relatively homogeneous way might suggest the shape of a characteristic curve.)

• What aging markers (health parameters?) are not altered by LT (long-term) CR? By ST (short-term) CR?

• Is there a summary of lifespan tests among mice?

• To what extent does losing, say, 20% of body weight have upon the calories required to function? Conversely, how does adding fat increase the caloric requirements?

• Is there a summary of lifespan tests among mice?

• What would be the lifespans of those who start CR very late in life... for example, a group of those who are 98 and who appear to be headed toward becoming centenarians*? If their CR-altered aging biomarkers are taken back to those of someone relatively young, will they nevertheless die within a few years, as predicted by actuarial statistics? (If lifetime calories are all that count, as predicted by the "Lifetime-Energy_Budget" model, we would expect them to experience little improvement in lifespan.)

* - Someone 98, having only a few more years to live at best, might have less to lose by trying CR than someone who is much younger.

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