Wednesday, October 29, 2014

Excerpt from an old article on CR relating to humans

“Speaking of humans,” Fontana added, “if you are lean because you are exercising, of course you are doing good, because you’re preventing types of diabetes, some kinds of cardiovascular disease and maybe some types of cancers. But the data suggest that calorie restriction is more powerful. And the people on C.R. are more powerfully protected from diseases than the exercisers.”

Fontana connected his point to his continuing observations of some Calorie Restriction Society members. “In terms of cardiovascular diseases — the No. 1 cause of death; 4 out of 10 people die of it in the U.S. and Europe — we know that they will not die of cardiovascular death,” Fontana said. His subjects have cholesterol around 160, blood pressure around 100 over 60, high HDL, low triglycerides and very low levels of inflammation. “So these people won’t develop these diseases,” he said. “And I think that’s an important finding. Because every day doctors are publishing hundreds of papers on circulation research and medications that are lowering blood pressure or cholesterol by a small bit. And here we have such a powerful intervention that is basically cleaning out the arteries.” At Tufts, Susan Roberts, the lead investigator, echoed this position, saying that the study will probably have greater effects than the average clinical trial. “I don’t know why anyone would take drugs when they could do something like this,” Roberts said, referring to Calerie.-link

A nice article regarding CR in humans, this is only a small interesting bit.

On degrees of CR viable in longer lived animals

My next interview was so upsetting that it is difficult to write about, and it shows that CR can, in certain cases, lead to full-blown anorexia. I called Al at home; his voice was quiet and somewhat difficult to hear. I asked how many calories a day he ate (1,950, he said) and how much he weighed.
"Ninety-two," he answered. I hoped I'd heard wrong. "How tall are you?" I asked. "Five-four," he said. "But I used to be 5-feet-11." He paused. "Osteoporosis." His spine had compressed a full 7 inches—or perhaps he was bent over. I was glad we were on the phone and I couldn't see him.
Al, who is 59, said he began CR in 1989 after reading about it in a textbook co-written by CR guru Roy Walford. -link

It is likely that the CR performed here was more extreme and has now become more moderate.  Such examples suggest that extreme CR might not be recommendable for longer lived animals prone to bone loss over time.    
More moderate CR, combined with CR mimetics should be viable and not entail such side effects(adequate calcium intake and vitamin k2 should probably also be helpful).   Several CR mimetics are said to not be additive with maximal CR(around 65% restriction), but should likely have additive effect on more moderate CR.    An interesting compound that should hopefully be tested in mammals, is rhodiola, which is a compound that is additive with CR and even maximal CR in a species of insect.   The mechanisms of rhodiola are also of interest seeing as it can move some species' lifespan beyond maximal CR

nice global ilumination vid ue4

Monday, October 27, 2014

Nice quote on computational processes

A computational process is indeed much like a sorcerer's idea of a spirit. It cannot be seen or touched. It is not composed of matter at all. However, it is very real. It can perform intellectual work. It can answer questions. It can affect the world by disbursing money at a bank or by controlling a robot arm in a factory. The programs we use to conjure processes are like a sorcerer's spells. They are carefully composed from symbolic expressions in arcane and esoteric programming languages that prescribe the tasks we want our processes to perform.-link

 And the world is entering an age, were the most powerful of all such is about to come into existence, where the design of artificial minds become possible.  It is then that entities of immense capability can be summoned into this world.  

Monday, October 20, 2014

Nice quote on gene expression and calorie restriction

 "Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes."-link

Effects seen in liver of rodents, reversal of most age related changes in gene expression, if I'm not mistaken.
LTCR long term calorie restriction
STCR short term calorie restriction

Saturday, October 11, 2014

Nice sciencedaily article from earlier this year

Monkey caloric restriction study shows big benefit; contradicts earlier study

...The study of 76 rhesus monkeys, reported Monday in Nature Communications, was performed at the Wisconsin National Primate Research Center in Madison. When they were 7 to 14 years of age, the monkeys began eating a diet reduced in calories by 30 percent. The comparison monkeys, which ate as much as they wanted, had an increased risk of disease 2.9 times that of the calorie-restricted group, and a threefold increased risk of death.
"We think our study is important because it means the biology we have seen in lower organisms is germane to primates," says Richard Weindruch, a professor of medicine at the School of Medicine and Public Health, and one of the founders of the UW study. "We continue to believe that mechanisms that combat aging in caloric restriction will offer a lead into drugs or other treatments to slow the onset of disease and death."...
 Weindruch also points to some results from the NIA that seem to contradict the "no significant result" analysis. Twenty monkeys entered the NIA study as mature adults, 10 in the test group and 10 in the control group, and five of these (four test monkeys and one control monkey) lived at least 40 years. "Heretofore, there was never a monkey that we are aware of that was reported to live beyond 40 years," Weindruch says. "Hence, the conclusion that caloric restriction is ineffective in their study does not make sense to me and my colleagues."...-link
 Calorie restriction seems to be showing noticeable benefits on primates.


Thursday, October 9, 2014

a response in Josh Mitteldorf's blog

Regards Telomeres:
while I'm not sure if the measurements are reflective of increases throughout, say stem cells, it has been claimed that a vegetarian diet combined with even modest low intensity exercise can increase the length of telomeres in humans by a noticeable amount.

Regards Thymus:
I've heard that some doses of melatonin are able to reverse thymic involution in nonhuman animals.

Regards natural substances, we have to remember that some can interact with regulatory proteins and alter gene expression.

For example I believe that CR is at least in  part  probably an artefact of metabolic regulatory networks and not a primarily evolved survival mechanism, it works up to around 65% restriction in some animals but requires optimal nutrition unlikely in any natural environment at that level of restriction.   If you can mess directly with the signaling pathways there's no telling what the limits are, as you wouldn't be bound by minimum survival necessary caloric intake limits, and multiple substances are emerging that appear to affect the signalling directly such as nicotinamide riboside, and the various partial cr-mimetics(resveratrol, fisetin, pterostilbene,etc).  There's also probable dietary means of also activating these signaling pathways such as low methionine diets, which can be combined with the substances and probably yield additive effect.

The telomere study wasn't large but iirc, it took measures after five years, which should give time for changes to accumulate,  between comparison groups and had noticeable differences

"The group that made the lifestyle changes experienced a “significant” increase in telomere length of approximately 10 percent. Further, the more people changed their behavior by adhering to the recommended lifestyle program, the more dramatic their improvements in telomere length, the scientists learned.

By contrast, the men in the control group who were not asked to alter their lifestyle had measurably shorter telomeres – nearly 3 percent shorter – when the five-year study ended. Telomere length usually decreases over time."-

"I believe CR is an evolved mechanism for population regulation. Think of it as aging extra fast when there is a temporary plentitude of food, so overpopulation is a risk. The idea that CR life extension only works with optimal nutrition has become part of the biological lore, but it has never really been tested. At the very least, there are big exceptions, as when insufficient protein and methionine help to ENHANCE life extension from CR."

While I don't remember the source I've also heard it must be gradually undertaken or else no lifespan benefits are seen if it is  introduced all of a sudden in adult organisms, in nature it seems sudden famine is more likely.  Also it seems to work up to about 65% in some animals, even if we were to assume no supplementation is necessary in more mild calorie restriction, it is unlikely there wouldn't be serious malnutrition at such extreme levels, yet it keeps on working past what would seem like natural environment nutrient limits.  
Regards methionine, iirc, it's believed to be one of the key signals of nutrient availability which is used by the mechanisms of cr, but it cannot be reduced beyond a certain point without severe side effects.

As for testing malnutrition CR I would imagine you consider CR not effective in humans or else some of the poorest on earth would be breaking records, which they're not and would serve as a test if it is effective in humans.

Tuesday, October 7, 2014

a response in a thread on kurzweilai forums

[quote]Most people imagine that shortly after the first human level AGI is created an SAI is destined to emerge shortly there after, one that is absolutely unfathomable to our puny little meat brains. When the truth is our brains could put Watson to utter shame (assuming they had a way to assimilate the data rapidly) if they were redesigned and optimized for a such narrow task..[/quote]
 While difficult, comparative genetics can show the modifications from simpler mammals like rodents, to primates to humans, and even among humans the differences bestowing greater intellect.   It remains an open question how straightforward the modifications are, is there a clear path or if they're highly specialized and totally unique  with each leap in capacity.   If it turns out that in general there has been a straightforward route of modifications to the neural wiring and computing algorithms employed in animals as their intelligence increases, then it will be possible to extrapolate the design choices forward to their theoretical limits.
[quote]If you speed up a monkey 100 fold, that monkey will just do monkey things 100x faster. I don't see why it should be all that different for humans.
Given 100xspeed up a human could master countless fields of science, with the plasticity of a child he could easily attain human native performance in countless languages, and with enhanced memory he could have encyclopedic knowledge of all he masters.    A monkey is a sublinguistic entity and thus limited in what it can endeavour, discover and accomplish, a human is not bound by such limitations.
[quote]Trying to turn a digital computer into a brain, though, that is an entirely different prospect. I would compare it to trying to modify a candle through step by step alterations (each stage of which functions well enough to be useful) until you have an electric light bulb. One can obviously make trivial similarities between candles and light bulbs (both provide illumination) just as one can with computers and brains (both process information) but the differences in design principles are so profound there really can be no evolution of one into the other.[/quote]
The difference is that it is assumed what the brain is performing is computation, if it is then like flight happens with planes without turning them into birds, a different architecture that is universal can also perform the same computation, because algorithms are substrate independent.    Of course if it is doing some spooky or magical thing that is not computation then it can only be approximated.
That is when you go into the camps of those who say physics is computable, including quantum physics, and not even quantum computers are more powerful than traditional turing machines albeit faster at certain tasks, and those who say physics is not computable.   Even in the case of physics not being computable, it is said that it is not possible to physically build a computer that surpasses a turing class  computer, so the brain would have to not be a computer at all or  if so it would need to be some manner of hypercomputer or such claims would have to be flawed.

[quote]The difference between the the most idiotic of our species and our most accomplished has little if anything to do with the speed with which the brain "computes". Instead it has everything to do with the integrated models that are physically instanced within each particular brain.[/quote]
Both white matter quality and grey matter volume have been linked to iq.  White matter increases speed, but within a simulation it is possible for the communication to appear to occur instantaneously for the simulated entity.   As for increased grey matter, Increasing the number of elements is also trivial, and in a few decades we may have countless exabytes allowing for countless number of elements.
There are other variations such as the size of various divisions within the brain, in sensory areas making those with less allotment more suceptible to illusions in said modality.   There are also countless variations in many parts of the system at a molecular level, making some more prone to hostility, with worse or better memory, more faithful, easier to get addicted, etc