Slowing the aging process in mice slows the development of a mouse model for Alzheimer's disease.
Therapies that can keep us younger longer might also push back the clock on Alzheimer's disease, suggests a new study of mice in the December 11th issue of the journal Cell, a Cell Press publication.
"There's something about being youthful that protects us from Alzheimer's disease," said Andrew Dillin of The Salk Institute for Biological Studies. "People say that if you live long enough, you get Alzheimer's. But if that were true, mice that live longer should get the disease at the same rate. That's not what we found."
Biogerontologist Aubrey de Grey expects results like this one. He believes the most effective way to deal with the diseases of old age is to not grow old in the first place. A young immune system, cardiovascular system, et cetera will prevent lots of diseases that accompany old age. Stem cells and gene therapies that repair some of our aging pieces will prevent dysfunctions of those and other pieces.
The amyloid plaques still developed but had less of a toxic effect.
The researchers show that mice carrying human genes that cause them to develop Alzheimer's can be protected from that disease by turning down a pathway that is well known for its effects on aging. Surprisingly, the brains of the mice who were spared the cognitive, inflammatory and neural effects of Alzheimer's by reducing the so-called insulin/IGF signaling pathway were still riddled with amyloid plaques. However, those plaques were more tightly packed into larger clusters than they would otherwise have been.
To answer this intriguing question, he slowed the aging process in a mouse model for Alzheimer’s by lowering the activity of the IGF-1 signaling pathway. “This highly conserved pathway plays a crucial role in the regulation of lifespan and youthfulness across many species, including worms, flies, and mice and is linked to extreme longevity in humans,” he explains. As a result, mice with reduced IGF-1 signaling live up to 35 percent longer than normal mice.
Studies like this one make me wonder whether I should take resveratrol. However, one study found no effect on IGF-1 levels from resveratrol in mice. Anyone know of other studies that suggest resveratrol might slow brain aging?
Following two months of dietary intervention, we observed reduced IGF-1 levels in CR mice, but not in resveratrol treated mice (Figure 2B).
But resveratrol does alter insulin signaling pathways.
By Randall Parker at 2009 December 13 12:11 PM Aging Brain StudiesI agree with Aubrey de Grey, you treat the cause (aging) not the effect (diseases of aging).
About a year or two, I asked Michael Rae about resveratrol and he seemed to indicate that later studies showed that resveratrol just caused certain things to eat less, and therefore to experience some *unintended* CR. That was my understanding at least. He knows infinitely more about this than I do. I would follow up with him or Aubrey de Grey (asking him about Rae's views too).
From following link it's not so much that CR lowers IGF-1but it's a diet with low protein:
http://ouroboros.wordpress.com/2008/10/22/calorie-restriction-and-igf-1-in-rodents-vs-humans/#com-head
Also from this link for long life in humans it's not lower IGF-1 it's fewer IGF-1 receptors that is important:
http://scienceandreason.blogspot.com/2008/06/igf-1-calorie-restriction-exercise-and.html
IGF-1 is reduced when diet is restricted in any one of the essential amino acids.
Interesting that histone deacetylase inhibitors, like niacinamide, seem (in some animal models, and now in human trials) to improve memory in aged animals - especially since it appears to oppose effects of histone acetylases, such as some of the sirtuins and resveratrol.
Also interesting that another histone acetylase, CREB-binding protein (CBP), appears to be central to the anti-aging effect of caloric restriction. See:
"Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling"
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000245
Also, I recall at least one other paper showing extended longevity in some simple lab organism fed histone deacetylase inhibitors.
Very, very confusing. Maybe there is some optimal cycling of histone acetylation/deacetylation required to extend life span and stave off dementia?
All:
Kip, I think you're confusing something I said about resveratrol with some other supplement, here. I have no reason to think that it suppresses appetite, but I *do* have very good reason to think that it's of no great benefit -- and certainly, does not retard aging or mimic CR -- to normal, healthy mammals. Resveratrol got -- and, surprisingly, still gets -- lot of folks excited, based on tantalizing-looking preliminary research done in overweight, high-saturated-fat-and-sucrose-fed, diabetic mice, and also in mutant, cancer-prone ones; but when tested in normal, healthy mice, resveratrol reduced the burden of a small number of specific health parameters, but had no benefits in extending youthful lifespan:
http://www.eurekalert.org/pub_releases/2008-07/nioa-rft062708.php
http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413108001824
This failure to extend life in the face of some gains in specific health parameters is probably a mixture of two things: a failure to protect against *real* cancer (which kills an awful lot of mice), and probably a 'dark side' to resveratrol and/or its possible "target" in the body, the SIRT1 protein, such as some of the effects suggested in some of my Forums post, or this one on brain health:
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=113625
http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413108001824
Even before this study came out, there were already reasons to be skeptical of the claims for resveratrol, even in flies and worms, for reasons outlined on the Foundation's discussion forums:
http://www.methuselahfoundation.org/forums/forumdisplay.php?f=48
See also this post, which addresses a couple of rebuttals and very quickly cites some more recent unfavorable data:
http://www.imminst.org/forum/index.php?act=findpost&hl=&pid=343914
Some readers may react to this by saying that even if res didn't affect LS, it still affected health, which is still a good outcome. But the relevance of those specific outcomes to human supplementers' health is dubious. Resveratrol has some estrogenic effects, both directly as a phytoestrogen and indirectly as an aromatase modulator, which makes me nervous for reasons discussed in the prostate cancer thread in that methuselahfoundation post, and the bone protection may be through this very mechanism. Some of the other effects may also be artifacts, since the rodents' control chow lacks ANY polyphenols, so this may just constitute artificial replacement of effects people eating a basically healthy diet would already be getting with no supplements. And last, if they're protected from these diseases and age-related declines, why aren't they living longer? Normally, healthy animals don't just drop dead: you have to be sick first, and die of SOMETHING. So if they have a reduction in these health problems and don't live longer, is there something *else* going wrong to counterbalance the positive-looking effects?