**Rejuvenation
Update - Part I**

**April
7, 2004**

__Tonight's Calorie Restriction Presentation on
CBS' Evening News__

Tonight, on the CBS Evening News with Dan Rather, there was
some footage on calorie restriction at the end of the broadcast "Fewer Calories, Longer
Life?".

__Partial Rejuvenation__

A few weeks ago, I joined the Calorie Restriction Society.
I've learned a lot from being on the CR e-mail lists. One subject that has
become clearer is that of the partial rejuvenation that caloric restriction
provides. I didn't figure this out for myself, but I can't quote from the e-mail
of the very-smart individual who did because what appears on e-mail lists is privileged
information.

__An Interpretation of Dr. Spindler's Latest
Study__

In Dr. Spindler's latest study, his mice ate their fill, and
aged normally until they were 19 months old... the human equivalent of "60
to 65". Then they were put on a diet that restricted their calories 44%. In
human terms, this would be equivalent to dropping from 2,600 calories a day to
about 1,450 calories a day.. Finally, he followed them until they died. What Dr.
Spindler found in his latest "*Proceedings of the National Academy of
Sciences*" paper was that the remaining lifespan of the average
caloric-restricted mouse increased from 11.8 months to 16.8 months, give or take
a bit. In other words, caloric restriction increased the lifespan of the
average mouse by 5.0 months. So the average lifespan of his mice (presumably in
his control group) was 19 months + 11.8 months = 30.8 months. If we divide the 5
months of additional lifespan that caloric restriction bestows upon the average
mouse by the 11.8 months of the average mouse' additional lifespan, we arrive at
a lifespan increase for the average mouse of 42%, which is what has been quoted
in the press relases reporting on this study.

A second (and in my opinion, very important) fact that Dr.
Spindler discovered is that after his caloric-restricted mice had been
caloric-restricted for 2 months (and were 21 months old), their mortality rate
had dropped by a factor of 3.1.

__Shifting to Human Calenders__

Now I'm going to try to convert this into human equivalents
because my next number involves human mortalities. Also, in the end we're going
to want to know what this might possibly do for us, rather than what it does for
mice.

The articles about Dr. Spindler's results, quote the "60
to 65" equivalence for 19-month-old mice. That leads to some mighty
long-lived mice, but these mice were already "state-of-the-art" in
terms of natural longevity.

If I equate 60 human years to 19-month-old mice, I get a
mouse-to-human conversion factor of 60/19 = 3.15 human years/"mouse
month".

If I equate 65 human years to 19-month-old mice, I get a
mouse-to-human conversion factor of 65/19 = 3.42 human years/"mouse
month".

But the important thing is the approximate value of this
conversion factor, although it would be good to have a more accurate number.

The 2-month mortality reduction period in mice translates
into 6.3 to 6.84 years to reduce mortality by a factor of 3.1 for humans
starting caloric restriction at 60-to-65.

In other words, a human being starting caloric restriction at
60 would be 66.3 years old before caloric restriction fully reduced his mortality by a
factor of 3.1 A 65-year-old would be 71.84 years old before caloric restriction
fully reduced her mortality by 3.1.

Although it would take 6-to-7 years to fully effect the 3.1:1
reduction in mortality, I suspect that the lion's share of this mortality
reduction may occur within six months.

__Converting a 3.1 Reduction in Mortality Rates
to a Reduction in Effective Biological Age__

Now in humans, the mortality rate doubles every 8 years. This
is probably not exactly true, and it may break down in old age, when the
doubling time may change, but I'll use this number for the purposes of this
calculation since I'm trying to arrive at a concept more than a precise number.
(Of course, these studies are probably still preliminary, and there's nothing
that says that their results have to be directly transferable from mice to
humans, but we have to start somewhere. My guess is that they may agree somewhat
closely.)

Now if mortality doubles in humans every 8 years, and caloric
restriction reduced the mortality rate by a factor of 2, we could say that, from
the standpoint of mortality, we've subtracted 8 years from the biological age of
a 66.3 to 71.84-year-old human.

If caloric restriction reduced the mortality rate by a factor
of 4, we would have effectively subtracted 16 years from the "actuarial
age" of a human.

In practice, it reduced the mortality rate (in mice) by a
factor of 3.1. So how many years does that represent in human terms?

We could write:

3.1 = 2^(t/8).

Then if we take the decimal logarithm of both sides, we have
log(3.1) = t/8 * log(2). But

log(3.1) = 0.49136

log(2) = 0.30103, so that

0.49136 = 0.30103 * t/8, or

t = 8 * 0.49136/0.30103 = 8 *
1.6323 = 13.058 years = ~ 13 years

So from a mortality point of view, the CR diet should back up
humans aged 66.3-71.84 time frame by **13 years**.

Now mortality rates are an acid test of location along an
aging (survival) curve.

The 13-year figure-of-merit derived above would be the number
of years of rejuvenation that elders might be expected to reap if they started
caloric restriction at the beginning of old age.

__Converting the Remaining Lifespan of Average
Mice into Human Terms__.

Another, more-direct way to arrive at the overall effect of
late-in-life caloric restriction is to multiply the extension of the average
lifespan... 5 months... by the conversion factors 3.15 to 3.42. Presumably, this
number is greater than the rejuvenation effect because the caloric-restricted
humans would be aging slower going forward as a consequence of their caloric
restriction.

This gives a total lifespan extension of 15.75 to 17.2 years.
This would put the average caloric-restricted lifespan among humans entering
caloric restriction at the theshold of old age at, perhaps, 100.

__The Lifespan of the Longest-Lived 10%__

For the mean lifespan of the longest-lived decile of Dr.
Spindler's mice, caloric restriction extended their lifespans from 37.6 months to
43.6 months, or about 6 additional months. In human terms, that would correspond
to 18.9 to 20.5 years. If I take the mean of the longest-lived decile in humans
to be 88 (I'm making a wild guess), then CRON started at the beginning of old age
would take these survivors to 107 to 108.5 years. (I'm certainly finagling here.
37.6 months multiplied by 3.15 translates into the awesome age for the mean of
the longest-lived human decile of 118, and 37.6 months times 3.42 leads us to
129 years! These numbers are much too high for the mean of the longest-lived
human decile even if, like the mice, they were placed on an optimal diet! And a
CRON diet, started at 60 to 65, would be expected, for the longest-lived decile
among humans to 137 and 149 years, respectively.)

So it seems to be true: going on a caloric-restricted program
late in life can subtract more than a decade from your biological age! What a
windfall! Of course, this is all counting chickens, but it's nice to have something
to dream on.

Sounds great. It has my vote. Bring on the cake and
cookies--oops! How about hot chocolate with green tea in it?

I think the Life Extension Foundation can take great pride in
having sponsored Dr. Spindler, and having sponsored a watershed discovery that
should do wonderful things for the world.

**Part II
Part III**

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