Rejuvenation Update - Part III

April 11, 2004

Is Partial Rejuvenation Here Now?
    Today, I reviewed two interviews with Dr. Stephen Spindler to make sure that I hadn't been mistaken about the partial reversal of aging in old mice. But he states exlicitly several times in these interviews that we're talking about partial rejuvenation in the aged, and not just about the slowing of aging. But he's quite explicit about the fact that this is partial rejuvenation and not just retardation of aging, as has been thought in the past. Here's an actual passage from the first interview:

L.E.: So if you see an anti-aging benefit in these mice, it's a true anti-aging benefit, not just a correction of some life-shortening genetic defect. Now, let's attack this from a slightly different angle. Since the animals were already extremely old when you imposed short-term calorie restriction on them, and since their gene expression profiles appeared more like those of young animals after the short-term calorie restriction, it seems inescapable that calorie restriction is not only able to slow age-related changes, but that it is able to reverse age-related changes as well. And it is able to do so over a remarkably short period of time.

S.S.: I think that may be our most significant contribution here.

L.E.: Has anyone else ever suggested that calorie restriction could reverse aging, not just slow it? Or is your finding truly unique?

S.S.: As far as I know, there had been no suggestion in the literature before our study that calorie restriction could reverse age-related changes in gene expression. I think the assumption has been that it prevents deleterious age-related changes in gene expression. It had been our assumption as well, and we've published a number of papers on gene expression where we just assumed that calorie restriction was preventing deleterious changes. What these studies showed for the first time was that in fact that assumption was incorrect. Calorie restriction can reverse the majority of the deleterious age-related changes in gene expression that we found.

L.E.: That's revolutionary and very interesting.

S.S.: There's another issue here too, and that is that we only did two weeks of extreme caloric restriction and two weeks of mild. We're now looking to see if we can find early responding genes, late responding genes and genes that may be in the middle, or genes that may require life-long caloric restriction in order to prevent a change.

L.E.: So, for example, if the short-term calorie restriction were made a bit longer, it might work even better.

S.S.: That's true. I think there's the chance too that if we do this in younger animals, it is possible it will be even more effective, since they will not have accumulated damage throughout their lives beforehand.

L.E.: There would be less damage to reverse.

S.S.: Yes.

L.E.: In general, is it true that caloric restriction started earlier in life, if done properly, leads to longer life span extension and stronger anti-aging changes?

S.S.: There are papers in the literature that indicate that it is true that calorie restriction earlier in life has a bigger impact on lengthening life span and decreasing the onset of age-related diseases than even longer calorie restriction imposed later in life. Nevertheless, our study shows that very late in life in very old animals calorie restriction will rather quickly start to reverse bad changes in gene expression and send them back to youthful levels.

L.E.: So it's not too late for the older folks out there, for people who think they're over the hill, to do something about aging. There's still hope.

S.S.: That's the best news for me.

     How increases in "youthspan" will scale as a function of time spent caloric-restricted, I'm not sure, but it looks as though the benefits for octogenarians can be substantial. While this seems unfair to those who have restricted their calories throughout much of their adult lives, it will broaden the base of public support among those who most urgently stand to gain from such interventions, and who are also best endowed to fund research in this area: our elderly. (Actually, people who start caloric-restriction early in life come close to realizing the full extent of life extension through caloric restriction, which is about twice that of those who start caloric-restriction later on.)

Metformin: Another String to the Bow
    I called my sister tonight and learned that my brother-in-law is taking metformin. My brother-in-law is an adult-onset diabetic, an affliction he shares with his mother and his grandmother. In 1973, he suffered a mild heart attack. He quit smoking, but was in a high-pressure job working for a company that was on its way to eventual bankruptcy. After being laid off in 1988, he suffered a crippling stroke in 1989 that has left him partially paralyzed. Still, that was 15 years ago, and it's a testimonial to something that he hasn't had a second, fatal stroke.
    Dr. Spindler and his associates discovered that the diabetes drug, metformin, produced most of the same genetic aging reversals as caloric restriction.
    No wonder lifespans are going up!
    Anything that can be taken as a simple pill is going to be well-received.

Resveratrol
    Now that Longevinex has made available a bioactive resveratrol capsule, it needs to be tested to see if it can trigger the changes in aging biomarkers induced by calorie restricion. If it is in humans the long-sought caloric-restriction mimetic, then it should generate precisely the same gene changes as calorie restriction. What will be required will be a randomized, prospective, placebo-controlled, six-month pilot test.

IGF-1
    Another promising target for age remediation might be Insulin Growth Facotr-1 (IGF-1). I don't know enough about it to be dangerous just now, but perhaps in a few more days, I can put mistate what it's all about.

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