A new drug that is a thousand times more powerful than resveratrol:
In the study, scientists fed the mice a high-fat, high-calorie diet mixed with doses of SRT1720 for approximately 10 weeks. The mice were given 100 or 500 milligrams of fat per kilogram of body weight each day (a high dose even for humans). The mice did not exercise regularly, although the scientists tested the animals' exercise capacity, or endurance, by making them run on a treadmill. "The mice treated with the compound ran significantly longer," says Auwerx. The drug also protected the animals from the negative effects of high-calorie diets: metabolic disorders, obesity-related diseases, and insulin resistance. It even improved the mice's cholesterol.
It is significant that the drug mimics the effects of a calorie-restricted diet, since this has previously been tied to increased life expectancy, says William Evans, a professor of geriatric medicine, nutrition, and physiology at the University of Arkansas for Medical Sciences.
It's as if the couch-potato mice underwent a strict diet and exercise regime, says David Sinclair, a biologist at Harvard Medical School, in Boston, who is one of the cofounders of Sirtris but was not involved in the current study. The new study "is a major step forward, showing that we can design and synthesize potent, druglike molecules that could slow down the aging process," says Sinclair.
I think that people are going to be amazed at the life-extension and health advances coming along in the next few years. It makes it all the more the shame that we continue to lose people who we might save if they could just hang on long enough.
OK, where can I get a video of these mice on treadmills? Sorry for getting off-topic.
All the medical benefits of calorie restricted diets, and none of the downsides, can be had for the price of skipping a couple meals twice a week. Intermittent fasting is the way to go; no need for drugs.
http://www.proteinpower.com/drmike/intermittent-fasting/
Is there actually any evidence of resveratrol extending lifespan in metazoans? Even the yeast and C. elegans evidence is unconvincing; to my knowledge, no one outside his lab has ever been able to duplicate Sinclair's results. Since the lifespan assay is so prone to experimenter-introduced bias, Linda Partridge actually went through and did a more thorough analysis of the putative lifespan extension, and didn't find anything. (A while back I actually ran an experiment myself using wild type C. elegans and some other worms treated with dsRNA to give them an unusual germ-cell 'cancerous' phenotype...didn't help with aging, or the cancer, for that matter.)
I'd be pretty leery about using large amounts of resveratrol (which is effectively what this new compound is) as a supplement. People have picked up all kinds of low-affinity (~micromolar) targets for it, with a variety of mechanisms, which isn't surprising, given its structure. In particular, it seems to hit the adrenergic receptors and affect Wnt signaling, which is ok in small amounts but you wouldn't want to deluge your system with this stuff.
Sounds promising, if validated. What are the side effects? Making that big an impact on metabolism without upsetting a balance is at best tricky.
Honestly, the idea that one single molecule can neatly throw a secret switch and make us all live 20% (say) longer, without so much as a nasty headache for side effects, boggles the imagination.
I mean...how on Earth would you explain the evolutionary biology here? Why would this secret switch that's never used have evolved? Why does the all-powerful key exist, available in the environment, but not in sufficient concentration to be noticed by primitive man? Just lying around, like the monolith on the Moon in 2001: A Space Odyssey, waiting for us to develop molecular biology...? If the thing did work, it would be the strongest evidence of God (or at least Higher Beings Guiding Us) since those vague Greek tales of a Jewish carpenter coming back from the dead.
I'm barely willing to believe that death (or rather lifespan) is controlled by evolved biochemical mechanisms, that it isn't just a question of everything wearing out and falling to pieces. But if so, it seems very likely, given the way everything else works, that there will be many intertwining and multiply redundant control pathways, and interfering with them all will be just about as complex and difficult -- maybe even not dissimilar -- to interfering with the control pathways that turn cells malignant.
Damn, now the Singularity Club is going to put me on probation again. Sorry.
I mean...how on Earth would you explain the evolutionary biology here? Why would this secret switch that's never used have evolved?
It may have some other purpose, and the longevity is simply an emergent property.
I'm not following you Rand. FOR GOD'S SAKE USE MORE WORDS. I realize you pride yourself on economy of language, and I admire it, as I bloody well should -- yes I can see all your other commenters laughing -- but geez Louise have mercy.
So...the longevity is an accidental side effect of the switch? Doesn't that seem inconsistent with the idea that longevity is controlled? I mean, if I merely close my door, an accidental shove could open it, but if I latch it, it takes a less likely accident -- a shove plus a poke in the right place -- and if I install a deadbolt and a key, then the chances of some accidental triggering sequence working gets really remote. The more control over the event I exert, the more specific the pathway for it to happen deliberately, the less likely an accidental trigger. If longevity is under very solid biochemical control -- so solid no tribe of isolated Indians smoking strange regional mushrooms accidentally triggered it and all lived to be 180 -- then how can this accidental trigger exist? In short, if accidental triggering is even possible -- why only one accidental trigger? Should be none or many, I would think.
I'm sorry, Carl, but you seem to be under the misapprehension that I've given this a lot more thought than I have. It's just an interesting news article I posted. ;-)
Carl:
Who says it's accidental?
It's at least plausible that slow aging is a good genetic strategy during extended (decade-long?) famines (when there just aren't resources to spare for child-raising), but bad during times of plenty (you want to go ahead and pass your resources on to offspring who are really young, not just well-preserved).
I mean...how on Earth would you explain the evolutionary biology here? Why would this secret switch that's never used have evolved?
That's an interesting question...if you haven't had the chance, I recommend the book Between Zeus and the Salmon, which details the selective pressures that may have allowed aging to evolve the way it did. In particular, why is it that humans live so much longer than our closest evolutionary relatives, the chimpanzee? They present a number of arguments, but the one I found most convincing was Steven Austad's old point: every ATP we spend repairing ourselves is an ATP we're not using to try and reproduce.
I will check it out, with thanks, Jack.
why is it that humans live so much longer than our closest evolutionary relatives, the chimpanzee?
Well...in the first place, who says we do? We're not really clear on human lifetime in the wild, nor on chimpanzee lifetime if they had the brains to spend the last 40,000 years developing a science of chimp medicine.
But even accepting the premise -- I'm not fully clear on why there should be any smooth variation of lifespan with percent correlation of DNA. Seems to me genetic variation is more quantum, more jumpy, than that.
As for what kind of evolutionary pressures...? Well, maybe it goes hand in hand with our unusual retention of childhood plasticity, presumably an advantage because it allows us to keep learning, and to reprogram our societies (full of plastic individuals) to meet changing conditions very rapidly.
In essence, we partly replace natural selection of our genes with natural selection of our memes. Since software is cheaper and faster to redesign than hardware, we end up combining the rapid evolutionary responsiveness of the short-lived fecund species (although its really our social myths that breed and die so fast) with the ability of the long-lived low-fertility species to be stingy in its resource consumption.
"I mean...how on Earth would you explain the evolutionary biology here? Why would this secret switch that's never used have evolved?"
Anything that keeps you exceptionally healthy signifigantly *later* than the time when you've probably reproduced and raised those young, won't be particularly selected for, even if you (or I) as individuals might appreciate it. (conversely, it's hard to inherit a genetic trait that kills those with it before puberty)
"Why does the all-powerful key exist, available in the environment, but not in sufficient concentration to be noticed by primitive man?"
'Primitive Man' may well have been too busy dying (or trying not to die) of something else, to notice wether someone (even themselves) who consumed a lot of X, seemed to live astoundingly longer and healtiier. Indeed, just hitting *40* might've been their idea of 'old.' Famine, predators, infections, etc., were liable to get you sooner.
Even today, someone who, unknown to themselves, had traits that kept them from 'aging' past middle age, but had no other special traits...could still get run over by a truck before it's observed that they still look like 35 at 90.
Anything that keeps you exceptionally healthy signifigantly *later* than the time when you've probably reproduced and raised those young, won't be particularly selected for, even if you (or I) as individuals might appreciate it.
Ah no, Frank, that's where you're wrong. You've been listening to too many evolutionary biologists who only work with fruit flies. Google "The Grandmother Effect" for an eyeful. In essence, the observation is that, in a highly social society such as ours, where the success of a young person can be enormously enhanced by the favorable actions of a much older "mentor" and "guardian," there is a lot of post-reproductive years natural selection pressure.
In essence, genes for living long past your fertile years but retaining your ability to socially compete and acquire social power lets you significantly enhance, as a grandparent, the reproductive success of your children. Hence, those genes prosper. Genes that code for crappy grandparenting, or death right after fertility, or a lack of ability to rise to senior management levels, are at a disadvantage, because no grandparents help the parents out. Note that it's key that the genes also turn off your own fertility, because otherwise your later children would compete directly with your earlier children, and your grandchildren would be at a disadvantage. Hence menopause turns off fertility well before senescence and probable death.
Well...in the first place, who says we do? We're not really clear on human lifetime in the wild, nor on chimpanzee lifetime if they had the brains to spend the last 40,000 years developing a science of chimp medicine.
I believe humans in the wild have comparable maximum lifespans to humans living in a modern society. The enormous improvements in average lifespan from modern medicine mostly stem from decreased childhood mortality. I can't think of where I'm getting this from, though, so I may be mis-remembering.
That said, one of the items discussed in the book I recommended (which is available for free as a digital copy) is the Grandmother Hypothesis, as you mention above -- the idea that existing in a society brings about its own selective pressures. In particular, one idea that's been advanced is that the evolution of language greatly reinforced this effect. This may account for some of the lifespan difference between chimps and humans. There are other examples of unusual selective pressures brought about by social organization, for example, what drove the evolution of eusociality in wasps?
In essence, we partly replace natural selection of our genes with natural selection of our memes.
So society creates a positive feedback loop for further socialization. That's an interesting point, and I hadn't considered it in that light before. The evidence I can think of off-hand certainly supports that idea.
Ming the Clam lived for 405 years and its organs and tissues have the same basic design as squid who only live for a few years. This clam managed to escape senescence. Being a creature that only stays in one place, whos offspring don't directly compete with it or each other (most of them die in the plankton while the survivors are dispersed throughout the ocean), having an indefinite lifespan where each additional year means more copies of itself is produced is evolutionarily advantageous.