Rejuvenation Update - Part II

April 9, 2004

Partial Rejuvenation Is Here Now!
An Absolute Bombshell?
    I think this is an absolute bombshell. The fact that people of all ages can back up their ages by, e. g., 13 years, and can reduce their risk of dying to 1/3rd its value (as of 6 years in the future) is a windfall. Furthermore, I suspect that most of the gains in risk reduction are made in the first six months. When you stop talking about "mortality", and start talking about protection from cancer, heart attacks, strokes, Alzheimer's disease, Parkinson's disease, and adult-onset diabetes, I suspect it's going to reach out and grab a lot of people once they grasp what this can do for them. How much would it be worth to you to reduce your risk of all types of cancer by a factor of 3? Heart disease likewise? People strain at gnats to get a 20% or 30% decline in cancer prospects. Somebody who's 35 and at risk of heart disease could reset himself to 22, and postpone his prsent risk by 13 years. (Actually, he would be 41 before he got full coverage, and he would be resetting himself to 28, with the stipulations about six months possibly providing partial benefits, as mentioned in Part I.)
It's Been There All Along
    In retrospect, it's been there all along, but I wasn't smart enough to tumble to it. In Dr. Walford's "Beyond the 120-Year Diet", his table on Page 44 lists some parameters that improved for the eight members of the Biosphere II crew after six to eight months on a caloric-restricted, optimal nutrition diet. At the top of the list is a 14% weight loss. Then there is a list of other parameters such as blood pressure, fasting blood sugar, cholesterol, triglycerides, and a bunch of other less-well-known indicators such as fasting insulin levels.My first thought when I saw it was, "Well, that's probably because of the weight loss." Now I'm thinking that there's a lot more happening than just weight loss. People who are lean as a rail and can eat everything in sight without gaining weight wouldn't enjoy all these advantages (although I'm sure being trim and slim does its part for parameters such as blood pressure). As I've mentioned elsewhere, if caloric restriction merely slowed the rate of aging, these indices would simply deteriorate more slowly, but wouldn't back up.  
The World Hasn't a Clue That This Can Be Done
    Right now, there are probably only a handful of people in the world who know that caloric restriction can partially rejuvenate anyone. It takes some digging to pull this understanding out of the research papers. This is like special relativity in 1910, or general relativity in 1920. I predict that when this message gets out to the general public, it will create a furore. This is not to say that a lot of people will adopt caloric-restriction. It's been estimated that only one in a thousand has the psychological profile necessary to keep their weight down to that of young adulthood, and to eat just enough food to keep them from losing more weight rather than trying not to eat so much food that they regain their weight. But there will be some, and the very fact that this can be done should stimulate widespread public interest and amazement.
Question:  Are you saying that it makes no difference how old you are when you start caloric-restriction, or how long you've been on it, everybody will enjoy the same age reduction (~13 years), and the same extension in life span?
Answer:  That's my interpretation, I'm basing it on skimpy data. Dr. Spindler's 2001 study showed that 4 weeks of caloric restriction (2 weeks at 20% restriction, 2 weeks at 40% restriction) caused, in 35-month-old mice, about 70% of the gene changes seen in a long-term caloric-restricted, 27-month-old control group that had been caloric-restricted since weaning. 
    There are three other, caloric-restriction-later-in-life studies that began at 12 months of age (lower 30's in humans?). 
    One of them involved roly-poly-fat mice (Krispy Kreme addicts?) put on 41% caloric restriction that exhibited 31- and  40.6-month normal (fully fed) lifespans for the average and long-lived mice, respectively, and 36.9- and 45.1-month lifespans at 41% caloric-restriction. (Caloric restriction brought them down to normal weight.) The lifespan increases were 5.9 months for your average roly-poly mouse, and 4.5 months for the mean lifetime of the longest-lived decile. Both the caloric restriction and lifetime extensions were similar to those seen in Dr. Spindler's group, below.
    The second study featured mice that wre 26% caloric restriction, and were living relatively high-on-the-hog. The average lifespan among the fully fed mice was 30 months, with the longest-lived living 37.7 months. The caloric-restricted mice lived, on average, 33.2 months, and among the longest-lived decile, 41.8 months, for life extensions of 3.2 and 4.1 months, respectively. 
    The third study is Dr. Spindler's study described in Part I.
    All three of these studies seem to me to point toward similar lifespan extension numbers and similar measures of (partial) rejuvenation. It's too bad that some of Dr. Spindler's calorically-restricted 35-month-old ladies couldn't have lived out their lifespans to see how much longer they would have lasted, but he probably didn't have enough mice for that, or a reason to expect that they would, possibly, have lived unexpectedly longer. (Who would have thought it?)
Question:  So why not live it up until you're old and then adopt caloric restriction when you turn 60?
Answer:  Uh--before you put on your party hat and head for the food bar at Sirloin Stockade, you might want to contemplate how little is known about this yet. These are just the first early phases of these studies. I suspect that people who start a CRON diet at an earlier age will be well-rewarded for their diligence. For example, mice that are put on a CRON diet at one month live about twice as long (10 months, equivalent to 30+ years) as those who begin a CRON diet at the 19-month threshold of old age (5 months, equivalent to 15+ years). Mice that are placed on caloric restricion at maturity accrue 90%-100% of the benefits of mice on lifelong caloric restriction, so these young CRONers may reap much greater benefits than Johnny-Come-Latelies like me. Also, throughout their lives, the CRON dieters will be strongly protected against cancer, heart disease, etc. And to the best of my knowledge, there haven's yet been any studies of what happens to the mortality of mice placed on a CRON diet at, say, 30 months of age. Will they awarded the same rollback in aging biomarkers as 19-month old mice.
    The only idea that makes me at all sanguine about that are the genetic changes that Dr. Spindler found when he "autopsied" his 35-month-old mice. 
Will This Sweep the World and Kick-Start the Field of Aging Reversal Research?
    I believe that this may jump-start the field of applied aging reversal, pumping in money for research. How can you make a case for pouring billions upon billions into cancer research when you could cut the risk of all types of cancer by a factor of 3 just through caloric restriction? Ditto for cardiovascular disease.
    As a 23-year NASA researcher, I believe it will take a few years to develop and expand a line item in federal budgets, but in my experience seeking and disbursing research funds, after a few years, worthwhile programs tend to become somewhat institutionalized. 
    And that brings us to the case of aging reversal pills.... pills that will produce the effects of caloric restriction, perhaps, without having to reduce caloric input (although, as I've said elsewhere, I suspect that if you get your metabolism operating in the efficient mode that characterizes caloric restriction, you're going to have to restrict your caloric input in order to avoid putting on weight). These pills exist right now and I'm taking them. I have a box downstairs in the refrigerator... Longevinex' resveratrol capsules. Longevinex resveratrol capsules are being studiously ignored by anti-aging companies and universities  because they want to develop their own patentable products that they can submit to the FDA as potential drugs. 
    What is needed are tests of Longevinex resveratrol with people who aren't on caloric-restricted diets to see if resveratrol triggers the same effects as caloric restriction. These tests will probably have to run for at least six months in order to measure the declines in the various biomarkers. Tbey may already be underway, but if not, they should be started.
    If resveratrol capsules can cut the risk of cancer, cardiovascular disease, diabetes, Alzheimer's disease, and Parkinson's disease by a factor of 3, who wouldn't want to take them?

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