Does fatty food increase longevity?
Aging of the organism appears to depend on food intake. I have previously pointed out that prolonging life can probably be achieved by preventing any overeating, even short-term. During a discussion on the X network, the well-known blogger Peter (@Peter_InNorfolk) shared a study examining the lifespan of rats on three diets: a standard diet (16% of calories from fat), a moderately high-fat diet (35% of calories from fat) without quantity restriction, and the same diet but restricted to the same caloric intake as the standard diet. He mainly commented on the shortening of lifespan on the unrestricted high-fat diet, which he attributes to the relatively high content of omega-6 linoleic acid in the fat, i.e., in lard.
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| Control – low-fat pellets, IHF – high-fat diet with isocaloric restriction, FHF – high-fat diet without restriction, experiment performed on male rats. |
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| The high-fat diet without restriction (FHF) slows metabolism and reduces heat production. |
However, from the previous post we know that the most critical phase of such a study is precisely the first days of the study, when rodents on a high-fat diet binge uncontrollably and thereby damage their adipose tissue and liver. They then are not able to store fats sufficiently quickly, and adipose tissue becomes insulin-resistant. This increases the amount of free fatty acids in the blood and damages cells.
If we want to study anything, the intake of fatty food must be limited, at least during the first days of the study. Here they did this by limiting calories to the intake level of the standard diet (pellets). This makes it possible to preserve healthy adipose tissue, which readily accepts fats and stores them quickly.
Thus, what seems far more interesting to me is the finding that a high-fat diet can allow lifespan extension, provided that healthy adipose tissue is preserved. In rats and fruit flies this can be easily achieved by limiting food availability. Would it work the same way in the partially unrestricted regime described in the previous post? I think yes. It is probably sufficient to limit the availability of fats to a short time window at the beginning of the active phase of the day. Carbohydrates can be consumed essentially ad libitum while maintaining a low rate of intake, i.e., spread over the entire day and available only in the form of hard pellets for rodents. But as far as I know, no one has yet tried this either in rodents or in humans.**
The study further investigated which specific fatty acids and enzymes are likely involved in lifespan extension. Surprisingly, they found that it is insufficient activity of PPARγ, i.e., the signal for fat storage. Yes, everything indicates that if adipose tissue is damaged by short-term overeating, it leads to a shortened lifespan. Fat storage is slowed, which leads to increased levels of all free fatty acids (FFA). But the researchers additionally identified one specific fatty acid, palmitic acid, as having the strongest effect on metabolism.
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| Differences in hepatic protein expression; IHF (high-fat diet with isocaloric restriction) reduces oxidative stress and inflammation. |
Palmitic acid (PA) is a saturated fatty acid with 16 carbons; its origin in the blood is almost exclusively from the processing of carbohydrates, fats, and proteins into acetyl-CoA and then reassembly into a new fatty acid chain. It therefore comes from the process of de novo lipogenesis. In this process, it is apparently very important to channel newly formed palmitate into further processes, i.e., incorporate it into triglycerides and export it, or elongate and desaturate it to oleic acid and burn it for heat or generate ATP molecules. If this does not work, the process stalls and PA levels increase, which blocks certain processes, increases oxidative stress, and shortens lifespan.
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| Palmitic acid (PA) added to an isocalorically limited moderately high-fat diet (IHF) reduces lifespan; RGZ (rosiglitazone) activates PPARγ and reduces oxidative stress; PPRC1 siRNA suppresses PPRC1 and the effect of RGZ. |
This was also confirmed in the next phase of the study, where, apparently to speed things up, the researchers used a fruit fly–based model. They determined that fruit flies have the longest lifespan at 7% fat content under an isocaloric diet. To verify the effect of palmitate, they added 3% PA to some groups and clearly observed a shortened lifespan and increased oxidative stress. They further identified the transcription factor PPRC1 as the main regulator, which is deactivated by the presence of PA. By increasing its activity, oxidative stress can be reduced and lifespan extended, whereas suppressing it restores oxidative stress and shortens life.
What conclusion can be drawn from this? Do not be afraid of a moderately high-fat diet. The only thing to keep in mind is that any major binge on fatty food can damage adipose tissue to such an extent that it stops functioning normally. Some fat cells enter a state of cellular senescence, and the overall rate of fat storage decreases. There will be nowhere to store fats, blood parameters will worsen, oxidative stress will increase, and lifespan will be shortened. But with a balanced intake adjusted to energy expenditure, a high-fat diet is safer and ensures a longer life than a low-fat diet. Research also shows that acetic acid (vinegar) can protect fat cells from damage. Even though it seems that under caloric restriction the fat composition of the diet does not matter, it is probably much safer to avoid seed oils containing a large percentage of omega-6 linoleic acid, which easily degrades and forms toxic aldehydes.
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| A beautiful demonstration of how apple cider vinegar, administered two weeks before the dietary change and during the switch to a high-fat diet (sudden overeating), protected fat cells from senescence. This is due to activation of SIRT1 and mobilization of antioxidant defenses. |
Addenum
So I'll add a small supplement again. I realized that a higher level of free fatty acids (FFA) interacts with the production of H2S by the enzyme CSE, in such a way that it significantly reduces H2S production. I wrote about it in an older post. This gives us the opportunity to speculate about the path by which life extension can occur. A lack of H2S means low S-sulfhydration of the enzyme eNOS, which produces nitric oxide (NO). This is involved not only in vasodilation, but probably also in the extension of life induced by changing the composition of proteins, e.g. by supplementing branched-chain amino acids (BCAA). In a study that investigated the connection between BCAA and lifespan, it turned out that the activator of the effects of BCAA is the enzyme eNOS, so I would add that it is its S-sulfhydration that ensures a longer lifespan. I don't have direct evidence, but this path seems the most likely to me so far.
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References:
An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila
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