Re: Life extension (was Chips: was Anchovy experiment)

[Guest guest]

In a message dated 2/26/2005 3:02:38 PM Eastern Standard Time,

Idol@... writes:

From the evidence I've seen, it's a fallacy in several ways:

(a) Calorie restriction appears to be most effective only for very

primitive species, such as certain worms.

_____

I haven't read up on it much, but calorie restriction seems to be

particularly effective for rodents as well. What animals have you seen for

whom it

isn't effective?

____

( The higher up the complexity ladder you climb, the less effective it

apparently is.

© The supposed gains in lifespan observed in calorie-restricted complex

organisms in lab conditions appear to be merely the recovery of something

approaching the full natural lifespan of those animals due to the reduction

in consumption of harmful food (animal chow as opposed to natural,

wholesome foods) chimps being one prominent example thereof.

____

The newer research on intermittant fasting-feasting helps to clarify a few

misconceptions about earlier calorie-restriction work, including this one.

The intermittant f/f rodents did NOT eat less food than their ad libitum

counterparts, nor their pair-fed counterparts (those whose food intake was

controlled to equal the intermittant f/f but who were not on a fasting

schedule), yet

had dramatic life extension equalling the CR rodents.

This shows that the benefit is NOT a result-- even a partial one-- of eating

less bad food.

Other clarifications include showing that the benefits with respect to life

extension and cancer immunity are NOT tied to the decrease in IGF-1 levels of

CR rodents, because intermittant F/F rodents get the same benefits with a

concomitant INCREASE in IGF-1.

To clarify this point, the F/F rodents do not simply fast periodically, but

FEAST as well. The two studies I read had them on an every-other-day fasting

schedule, and they ate ad libitum on the alternating days, during which they

made up for the fasting and ate roughly twice what the ad libitum group

would eat in one day.

_____

(d) The anemic life lived by calorie-restricted higher animals isn't at

worthwhile even if they are living longer than their healthy wild brethren,

which they apparently aren't.

____

I don't know about the issue with lab vs. wild, and I'd appreciate further

info on it if you have references. Given that the F/F research shows that the

benefits are not due to less bad food, it seems at least *plausible* that

the wild brethren would experience benefits on such a schedule in addition to

the benefits of better food. Secondly, we must consider the possibility that

the wild brethren ARE on a F/F schedule, so we cannot answer this question

until we do lab experiments where all-wild food types are used, but the feeding

schedules are controlled.

But I do want to point out that according to the intro of an article in

_Neuron_ of late last year (the article itself was on life extension in c.

elegans via a knockout of several genes relating to gustatory and olfactory

sensation), research indicates that resumption of a higher calorie diet resumed

reproductive capacity in CR animals EVEN AFTER times where " normal " animals of

the same species would have lost their reproductive capacity. So it seems from

this that the loss of reproductive capacity is not actual harm done, but a

calculated *suspension* of reproductive capacity by the body.

>Intermittent

>fasting/feasting animals have the same life extention benefits as

>calorie-restricted ones, but are much healthier in many respects, and

>have higher than

>normal, rather than lower-than-normal, concentrations of growth factors.

I

>haven't read anything, but suspect that their reproductivity remains robust

>just as their growth capacity does, unlike the temporary compromises that

>calorie-restricted animals experience.

Inasmuch as the tradition of fasting appears to be bound up with notions of

" cleansing " and " purifying " oneself, and inasmuch as fasting does appear to

be useful, at least for some people, for ridding themselves of certain

accumulated toxins, it seems likely to me that fasting is more likely to be

of use to people eating poorly than to be people eating ideally.

But who knows. It's an infant field.

____

I agree. But I think there is much more than purifying toxins. I think the

periodic lack of stimulation of insulin increases insulin sensitivity, for

example. The periodic ketosis induced by fasting appears to have

neuroprotective results. There are also neuroprotective results of a

*different* kind

that are NOT due to increases of beta-ketoglutarate in the brain but we don't

know what they are due to. Neurons of both CR and F/F mice have increased

resistance to excitotoxins, and the F/F have better resistance than CR and also

resistance to two different types of excitotoxic stress rather than one type

that CR mice experience. It is hypothesized that one type is due to the

increased levels of beta-ketoglutarate in the F/F, but since CR mice exhibit

*drops* in beta-ketoglutarate, the resistance they experience must be due to

something else.

Also, F/F mice have increased IGF-1 over controls (yet less cancer,

disputing the supposed connection between IGF-1 and cancer), so there may be

benefits

of F/F to quality of life, growth, etc, beyond life extension, unlike the

tradeoff between the two that CR demonstrates.

____

>The fasting-feasting phenomenon seems to indicate that growth and

>reproduction are not necessarily at odds with longevity, but it also seems

>to indicate

>that longevity requires additional factors beyond what robust

>health requires.

Well, are we talking genetic factors, like those which give women longer

life because men were selected for vigor and martial prowess to some extent

at the extent of longevity, or nutritional factors?

____

There are nutritional factors, I think. For example, there is some evidence

that growth suppressors help cancer after foci have been initiated and that

growth-inducers help cancer growth after cancer has been induced. So at

least *under some conditions* growth and cancer go hand in hand. But again,

the

F/F experiments seem to dispute that this is *always the case*.

But as you said, it's an infant field.

Chris

[Guest guest]

Chris-

>I haven't read up on it much, but calorie restriction seems to be

>particularly effective for rodents as well. What animals have you seen

>for whom it

>isn't effective?

Chimps -- but with mammals, particularly higher mammals, the real key piece

of information seems to be that whatever perceived " extension " is achieved

is actually just a partial or even near-complete restoration of the natural

lifespan of the animal, excluding factors like disease and accident of

course. AFAIK, though I haven't looked into it in depth, the same is true

of rodents.

>The newer research on intermittant fasting-feasting helps to clarify a few

>misconceptions about earlier calorie-restriction work, including this one.

>The intermittant f/f rodents did NOT eat less food than their ad libitum

>counterparts, nor their pair-fed counterparts (those whose food intake was

>controlled to equal the intermittant f/f but who were not on a

>fasting schedule), yet

>had dramatic life extension equalling the CR rodents.

>

>This shows that the benefit is NOT a result-- even a partial one-- of eating

>less bad food.

I think there are enough differences between the F/F rodents and the plain

CR rodents to suggest that the phenomena are too different to make that

assumption.

>Other clarifications include showing that the benefits with respect to life

>extension and cancer immunity are NOT tied to the decrease in IGF-1 levels of

>CR rodents, because intermittant F/F rodents get the same benefits with a

>concomitant INCREASE in IGF-1.

Yes, exactly! The physiological differences between them are profound

enough that I think it's unwise to generalize between them, at least until

we have a far greater understanding of what's going on. Perhaps the CR

animals have a lower toxic load, perhaps their detox mechanisms are less

stressed and therefore more effective, or maybe something about calorie

deprivation spurs detoxification. (Or maybe none of the above, or some

combination of factors.) Perhaps the F/F animals are getting detox

benefits from bouts of fasting, regardless of what's going on with the CR

animals. I don't know. I'm just speculating. But NOTHING I've read has

indicated that any of these animals are living longer than healthy wild

specimens. Where average lifespans are cited, researchers seem to be

making the mistake (or employing the deliberate deception) of not

controlling for disease, famine, accident, etc.

>To clarify this point, the F/F rodents do not simply fast periodically, but

>FEAST as well. The two studies I read had them on an

>every-other-day fasting

>schedule, and they ate ad libitum on the alternating days, during which they

>made up for the fasting and ate roughly twice what the ad libitum group

>would eat in one day.

Yes, I understand, but AFAIK they're all eating rat chow. And if what I've

read is true of all F/F and CR subjects -- namely that they're just

recovering the natural lifespan of their wild counterparts eating their

proper, species-appropriate diets (but controlled for disease, famine and

accident, of course) -- then the only real implication I can see at this

point is that we should be sure to eat the best, most nutritious possible diet.

It would, of course, be interesting to do some more CR and F/F research on

animals fed ideal, maximally nutritious foods, but I don't think anyone's

likely to do that -- at least not in a WAPF/NN sense. Unless of course you

and I become rich and mount just such a set of experiments. <g>

>I don't know about the issue with lab vs. wild, and I'd appreciate further

>info on it if you have references.

I don't have any handy, though I know the subject was discussed in a fairly

recent Wise Traditions, and I believe some references were cited

there. But I haven't kept anything I've read on the subject. If I have

time later I could go digging if you'd like.

>Given that the F/F research shows that the

>benefits are not due to less bad food, it seems at least *plausible* that

>the wild brethren would experience benefits on such a schedule in addition

>to

>the benefits of better food. Secondly, we must consider the

>possibility that

>the wild brethren ARE on a F/F schedule, so we cannot answer this question

>until we do lab experiments where all-wild food types are used, but the

>feeding

>schedules are controlled.

It is possible, and such experiments should be conducted, but in their

absence we have no real reason to try F/F eating ourselves. Particularly

since we're not rodents.

>But I do want to point out that according to the intro of an article in

>_Neuron_ of late last year (the article itself was on life extension in c.

>elegans via a knockout of several genes relating to gustatory and olfactory

>sensation), research indicates that resumption of a higher calorie diet

>resumed

>reproductive capacity in CR animals EVEN AFTER times where " normal "

>animals of

>the same species would have lost their reproductive capacity. So it

>seems from

>this that the loss of reproductive capacity is not actual harm done, but a

>calculated *suspension* of reproductive capacity by the body.

I'd just like to point out that this is IN A WORM. Worms are of a vastly

different order of complexity from people, and even species much closer

related often cannot provide generalized insights. Would you tell fat

people to go to sleep for several months -- without eating a morsel, of

course, or having a source of IV nutrition or anything like that -- because

bears hibernate? Of course not, but it would be a heck of a much better

guess than this worm generalization. The ONLY thing the worm results are

good for is providing some direction for future research, not any of the

grandiose pronouncements about life extension that have been coming down

the pike.

You know where I think meaningful life extension (i.e. not the kind we've

experienced to date, due to sanitation, emergency health care, antibiotics

and so on) will come from? A combination of factors, but none of them, I

think, will have to do with food scheduling: organ and system replacements,

detoxification (but on a finely controlled level, not a coffee enema) and

assisted repair and maintenance, i.e. from nanotechnological machines

and/or engineered microbes.

Profound life extension may have some very troubling implications, but hey,

that problem's for another age.

>I agree. But I think there is much more than purifying toxins. I think the

>periodic lack of stimulation of insulin increases insulin sensitivity, for

>example.

Perhaps, perhaps not.

>The periodic ketosis induced by fasting appears to have

>neuroprotective results.

Maybe, but it's relevant to point out that undisciplined low-carbers who

diet to lose weight, then return to their prior poor eating habits, then

diet to lose weight, etc., find that it's harder each time. This doesn't

*prove* anything about F/F, but it suggests caution and demands a line of

inquiry.

>There are also neuroprotective results of a *different* kind

>that are NOT due to increases of beta-ketoglutarate in the brain but we

>don't

>know what they are due to. Neurons of both CR and F/F mice have increased

>resistance to excitotoxins, and the F/F have better resistance than CR

>and also

>resistance to two different types of excitotoxic stress rather than one type

>that CR mice experience. It is hypothesized that one type is due to the

>increased levels of beta-ketoglutarate in the F/F, but since CR mice exhibit

>*drops* in beta-ketoglutarate, the resistance they experience must be due to

>something else.

Perhaps changes in the blood-brain barrier?

-

[Guest guest]

In a message dated 2/28/2005 12:28:30 PM Eastern Standard Time,

Idol@... writes:

It would, of course, be interesting to do some more CR and F/F research on

animals fed ideal, maximally nutritious foods, but I don't think anyone's

likely to do that -- at least not in a WAPF/NN sense. Unless of course you

and I become rich and mount just such a set of experiments. <g>

___

[Chris] Wouldn't it be great if Native Nutrition could do a yearly

" experiment drive " where we all pitched in to pay for some experiment to settle

some

issue that had been bugging us with questions?

Of course, who would let us use their lab? *sigh*

Chris