12 replies to this topic

[forever freedom]

Intermittent Fasting

And Research results of Mice under an IF Diet

[vyntager]

Lowering the temperature of your body ? At a lower temperature, chemical reactions will occur more slowly, about halved for each 10° C decrease in temperature. That'd theoretically allow you to live longer, as the chemical reactions of your metabolism would be slowed down.

But the human body isn't a test tube, so there's no clean, simple single chemical reaction happening down there, everything may be linked to a lot of other chemical reactions and metabolic paths.

Practically speaking, lowering your temperature, that'd mean hypothermia, and there are a lot of known and possible shortcomings to it. For instance, blood clotting.

You also need to cool down everything at the same rate, and at the same temperature, you can't allow internal organs to remain warm for instance. But if you get too low, you may expose yourself to serious cardiac issues. Also, your brain will be influenced, people suffering hypothermia may have hallucinations, be slurred, etc.

You could also make a case for the differences in how reaction rates will change following temperature decrease; for instance, let's imagine a metabolic process (process A) that creates a byproduct that is nefarious to your body, and is responsible for a part of the process of aging. Fortunately, there's another metabolic path (process B) that can break it down, not with enough efficiency to prevent it from damaging your body a little, but it won't be worse than that.
Now you decide to lower the temperature of your body, and it so happen that the process A rate of reaction does not diminishes as fast as that of process B. What it means is that the toxic byproduct will start accumulating faster than under normal conditions, leading to a possible decrease in your lifespan.

Still, I've never seen anywhere a study on how different temperature change particular metabolic paths, or the overall metabolome. So maybe the idea could still be developped further, I think it's a fascinating topic.

[s123]

Lowering the temperature of your body ? At a lower temperature, chemical reactions will occur more slowly, about halved for each 10° C decrease in temperature. That'd theoretically allow you to live longer, as the chemical reactions of your metabolism would be slowed down.

But the human body isn't a test tube, so there's no clean, simple single chemical reaction happening down there, everything may be linked to a lot of other chemical reactions and metabolic paths.

Practically speaking, lowering your temperature, that'd mean hypothermia, and there are a lot of known and possible shortcomings to it. For instance, blood clotting.

You also need to cool down everything at the same rate, and at the same temperature, you can't allow internal organs to remain warm for instance. But if you get too low, you may expose yourself to serious cardiac issues. Also, your brain will be influenced, people suffering hypothermia may have hallucinations, be slurred, etc.

You could also make a case for the differences in how reaction rates will change following temperature decrease; for instance, let's imagine a metabolic process (process A) that creates a byproduct that is nefarious to your body, and is responsible for a part of the process of aging. Fortunately, there's another metabolic path (process B) that can break it down, not with enough efficiency to prevent it from damaging your body a little, but it won't be worse than that.
Now you decide to lower the temperature of your body, and it so happen that the process A rate of reaction does not diminishes as fast as that of process B. What it means is that the toxic byproduct will start accumulating faster than under normal conditions, leading to a possible decrease in your lifespan.

Still, I've never seen anywhere a study on how different temperature change particular metabolic paths, or the overall metabolome. So maybe the idea could still be developped further, I think it's a fascinating topic.

A lower body temperature lengthens the lifespan of flies.

The effects of cold on the metabolic rates and lifespans of ectothermic flies have long been established. Loeb and Northrop (1917) made extensive studies showing that Drosophila at lower ambient temperatures lived longer. These observations have been replicated many times in several different insect species (Ragland and Sohal, 1975; Buchan and Sohal, 1981; Farmer and Sohal, 1987; Miquel et al., 1976). Contrasting these effects in ectotherms, however, a single study of the effects of cold exposure on longevity in rats indicated no significant influence on lifespan (Holloszy and Smith, 1986). This, perhaps, indicates that the impact of cold temperatures on lifespan in ectotherms acts via an effect directly on body temperature and is not mediated via an effect on energy demands. This interpretation is supported by observations on hamsters. Hamsters conserve energy during winter by hibernating and reducing their body temperatures. Lyman (1981) observed that if Turkish hamsters Mesocricetus brandti in the laboratory were prevented from hibernating then their increased energy expenditure and increased body temperatures were associated with a decrease in their lifespan.

Source: http://jeb.biologist...full/208/9/1717

Interesting is that low dosages of cyanide lengthens lifespan. Maybe because cyanide slows down the metabolism. But I wouldn’t advise you to eat cyanide.

[Ghostrider]

Since damage accumulates through metabolism, and slowing down metabolism has been proved to extend the maximum lifespan, what other ways other than CR or castration are there to extend the lifespan?

Castration extends lifespan? How?

[vyntager]

Thanks for the article

Interesting is that low dosages of cyanide lengthens lifespan. Maybe because cyanide slows down the metabolism. But I wouldn’t advise you to eat cyanide.

Hydrogen sulfide too btw

Also :

Hypometabolic states in mammalians (EU project, pdf report)

Castration extends lifespan?

For what I've heard, castration lengthens average life span, but as far as humans are concerned, people who underwent it were eunuchs, castrates, priests, etc. Maybe their lifestyle involved lesser risks (violent death, diet and lifestyle, social class) than those of their contemporaries ? Any study on animal models ? Those people were also more prone to being overweight, which wouldn't be good news healthwise.

[vyntager]

I'm done reading the article you proposed. I've also been searching for some of the articles it links to, namely the experiment with rats placed in cold water (holloszy, j.o. and smith e.k. : Longevity of cold-exposed rats: a reevaluation of the" rate-of-living theory" ) and a few articles by Selmann which seemed promising too, but all but one of those weren't free (scientific litterature ... ).

It seems that although the rate of living theory still has proponents, it has been for the most part ruled out, at the very least in it naive 1900's formulation. This doesn't mean that reduced metabolism (or more efficient metabolism, which blurs with being augmented metabolism in the mitochondrial uncoupling experiments) isn't positively correlated to a longer life expectancy.

Holloszy's experiment where rats were put in cold water only shows (as far as I can tell from the abstract) that indeed rats are endotherms and as such didn't see their temperature lower as that of, say, flies, and so too had an increase in their metabolism to fuel that endothermy. Conclusion : rats put in cold water don't live longer as flies do, because they don't see their temperature or metabolism fall... for what it's worth.
I'd be interested to see the same experiment conducted on animals whose thermoregulation has been shut down, or maybe whose metabolism has been impaired in some way or the other (hydrogen sulfide coming to mind, since it can inhibit cellular respiration).

The articles by Selman were interesting because it seemed like they linked exposure to cold to analyses of how different parts of the proteome were influenced. Clearly, I believe that a lower body temperature has the potential to lower the rate of all chemical reactions in the body (err if I'm not wrong, that's essentially what's happening in cryonics, the temperature is set low enough to practically put all chemical reactions/interactions in the body almost to a standstill ?). And all reactions in the body are slowed down, then at least naively you'd be induced to believe that the body will age at a slower rate (wear and tear theory withstanding).

Now I suppose there are a lot of negative practical considerations, and I'm immediately interested in two of them : whether there are regulation mechanisms which would attempt to counteract the effect of cold in the body (obviously there are, in endotherms, but I'd like to know about more than just temperature adjustment, for instance, how do lower temperatures affect genes expression and regulation ?).

Secondly, I'd be curious to know if the decrease in reaction rates/speed are the same for all reactions in the body; it seems to me it shouldn't be the case, and so what may be perfectly balanced in homeostasis at, say, 37° C for a human being, may not be so at a lower temperature, which may lead to serious issues (tocic byproducts accumulation, cellular repair impaired faster than cellular damage is lowered, etc.). If it is so, then up to which point would it be safe to lower the temperature of a living warm blooded organism, for short or long term exposure ?

People with experience/knowledge in cryonics, do you know any idea or relevant litterature about this ? Does it sound even sound, promising, or already tried and proved worthless ?


As for castration, I couldn't find the article with regards to mice, but I could get this article (which I'm going to read now) and this abstract.

[s123]

Reduction of core body temperature has been proposed to contribute to the increased lifespan and the anti-aging effects conferred by caloric restriction in mice and higher primates. Cooler biologically compatible core
body temperatures have also been hypothesized to combat neurodegenerative disorders. Yet, validation of these hypotheses has been difficult until recently, when it demonstrated that transgenic mice engineered to have
chronic low core body temperature have longer lifespan independent of alteration in diet or caloric restriction. This article reviews the literature and highlights the potential influence of core body temperature's governing role on aging and in the pathophysiology of neurodegenerative disorders in humans. What makes recent findings more significant for humans is the existence of several methods to lower and maintain low core body temperatures in human subjects. The therapeutic potential of "cooler people" may also raise the possibility that this could reverse the adverse-health consequences of elevations in core body temperature.

PMID: 18323756

[Mixter]

Inhibiting the thyroid by limiting iodine intake or by
appropriate foods (soy) can also bring down metabolism.

But slowing down metabolism without caloric restriction
is in practice not favorable. If you bring down your metabolic
rate at the same rate of calorie intake, you will be in not
only for obesity, but all the diseases that come with a
sluggish metabolism, including mitochondrial dysfunction
and atherosclerosis in the long time.

Slowing down metabolism additionally to CR might
be an option, but not with a normal 3000 calorie diet
and normal amounts of carbohydrates and fats.

LEF also has an upcoming article on how overeating not only
fills your stomach with excess calories but always at the
same time fills your arteries with sugars and fats, which
is exacerbated with slow metabolism and normal calorie intake.

[s123]

Inhibiting the thyroid by limiting iodine intake or by
appropriate foods (soy) can also bring down metabolism.

But slowing down metabolism without caloric restriction
is in practice not favorable. If you bring down your metabolic
rate at the same rate of calorie intake, you will be in not
only for obesity, but all the diseases that come with a
sluggish metabolism, including mitochondrial dysfunction
and atherosclerosis in the long time.

Slowing down metabolism additionally to CR might
be an option, but not with a normal 3000 calorie diet
and normal amounts of carbohydrates and fats.

LEF also has an upcoming article on how overeating not only
fills your stomach with excess calories but always at the
same time fills your arteries with sugars and fats, which
is exacerbated with slow metabolism and normal calorie intake.

Do you call a 3000 Kcal diet a normal one? I call it an American fast-food diet.

Edited by s123, 09 March 2008 - 11:37 PM.