Striking Accumulation Of PUFA In Aged Cells

haidut

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Peat has written many times about the changes that occur in "aged" cells. Those changes are virtually indistinguishable from the ones that occur in "sick" cells and are characterized by reduced mitochondrial number/size and a shift in lipid composition away from saturated and towards unsaturated fats. The crucial mitochondrial lipid enzyme cardiolipin (CL) comprises at least 20% of the lipids present in the inner mitochondrial membrane and its lipid composition determines it ability to both stabilize the inner mitochondrial membrane and proton flow across it as well as carry electrons between Complex III and Complex IV in the electron transport chain, and ensure proper structure of Complexes III, IV and even V. The more unsaturated the lipid composition of CL is the more vulnerable to attack/destruction by those electrons it carries is, and thus the more vulnerable Complexes III, IV, and V that contain CL are as well. In other words, more PUFA in the cell = more structural disintegration and less OXPHOS.

Thus, one would expect that aging (and disease) to be associated with a shift in cellular lipid composition in general (and CL composition in particular) towards PUFA. However, up until now evidence for age-related changes in cell lipid composition in favor of PUFA has been sparse to non-existent. The study below changes the status quo by demonstrating that senescence is characterized by a striking accumulation of PUFA inside cells. In fact, of the 19 types of triacylglycerols present in relative abundance in aged cells compared to adult ones, every single one of those glycerol types contained at least one PUFA member. The study does not go as far as to say that this accumulation is what drives aging because the study only looked at association, not causality. However, the fact that the level of PUFA accumulation was age-dependent implies causality and the knowledge about the effects of PUFA on CL function seals the deal, at least for me. The conclusion of the study was that lipids are far from passive when it comes to health and aging and they may regulate the very process of aging itself. I will go a step further and state that PUFA accumulation is the major cause of cell aging and reversing that accumulation likely restores a cell's biological age back to youthfulness.

Regulation of lipids is central to replicative senescence - Molecular BioSystems (RSC Publishing)

"...Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence. Based on the transcriptome analysis, we propose that the activation of CD36-mediated fatty acid uptake and diversion to glycerolipid biosynthesis could be responsible for the accumulation of triacylglycerols during replicative senescence."

As cells age, the fat content within them shifts - University at Buffalo

"...As cells age and stop dividing, their fat content changes, along with the way they produce and break down fat and other molecules classified as lipids, according to a new University at Buffalo study. “Traditionally, lipids have been thought of as structural components: They store energy and form the membranes of cells,” says G. Ekin Atilla-Gokcumen, PhD, an assistant professor of chemistry in UB’s College of Arts and Sciences. “Our results add to evidence that lipids may actually play a much more active role in the body, in this case, in the process of replicative senescence, which is linked to cellular aging. This is a new, emerging field of study.”

"...When the researchers compared the lipid content of young cells to older cells, some interesting trends emerged. In senescent cells, 19 different triacylglycerols, a specific type of lipid, accumulated in substantial amounts. These increases occurred in both lung and foreskin fibroblasts, showing that such changes are not limited to a single variety of cell."

"...The study found that during cellular senescence, the accumulation of triacylglycerols corresponded with a significant increase in the levels of genes involved in responding to oxidative stress...All had a remarkably similar structure, featuring long chains of fatty acids, including at least one polyunsaturated fatty acyl (PUFA) chain."
 

sun-maid

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Peat has written many times about the changes that occur in "aged" cells. Those changes are virtually indistinguishable from the ones that occur in "sick" cells and are characterized by reduced mitochondrial number/size and a shift in lipid composition away from saturated and towards unsaturated fats. The crucial mitochondrial lipid enzyme cardiolipin (CL) comprises at least 20% of the lipids present in the inner mitochondrial membrane and its lipid composition determines it ability to both stabilize the inner mitochondrial membrane and proton flow across it as well as carry electrons between Complex III and Complex IV in the electron transport chain, and ensure proper structure of Complexes III, IV and even V. The more unsaturated the lipid composition of CL is the more vulnerable to attack/destruction by those electrons it carries is, and thus the more vulnerable Complexes III, IV, and V that contain CL are as well. In other words, more PUFA in the cell = more structural disintegration and less OXPHOS.

Thus, one would expect that aging (and disease) to be associated with a shift in cellular lipid composition in general (and CL composition in particular) towards PUFA. However, up until now evidence for age-related changes in cell lipid composition in favor of PUFA has been sparse to non-existent. The study below changes the status quo by demonstrating that senescence is characterized by a striking accumulation of PUFA inside cells. In fact, of the 19 types of triacylglycerols present in relative abundance in aged cells compared to adult ones, every single one of those glycerol types contained at least one PUFA member. The study does not go as far as to say that this accumulation is what drives aging because the study only looked at association, not causality. However, the fact that the level of PUFA accumulation was age-dependent implies causality and the knowledge about the effects of PUFA on CL function seals the deal, at least for me. The conclusion of the study was that lipids are far from passive when it comes to health and aging and they may regulate the very process of aging itself. I will go a step further and state that PUFA accumulation is the major cause of cell aging and reversing that accumulation likely restores a cell's biological age back to youthfulness.

Regulation of lipids is central to replicative senescence - Molecular BioSystems (RSC Publishing)

"...Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence. Based on the transcriptome analysis, we propose that the activation of CD36-mediated fatty acid uptake and diversion to glycerolipid biosynthesis could be responsible for the accumulation of triacylglycerols during replicative senescence."

As cells age, the fat content within them shifts - University at Buffalo

"...As cells age and stop dividing, their fat content changes, along with the way they produce and break down fat and other molecules classified as lipids, according to a new University at Buffalo study. “Traditionally, lipids have been thought of as structural components: They store energy and form the membranes of cells,” says G. Ekin Atilla-Gokcumen, PhD, an assistant professor of chemistry in UB’s College of Arts and Sciences. “Our results add to evidence that lipids may actually play a much more active role in the body, in this case, in the process of replicative senescence, which is linked to cellular aging. This is a new, emerging field of study.”

"...When the researchers compared the lipid content of young cells to older cells, some interesting trends emerged. In senescent cells, 19 different triacylglycerols, a specific type of lipid, accumulated in substantial amounts. These increases occurred in both lung and foreskin fibroblasts, showing that such changes are not limited to a single variety of cell."

"...The study found that during cellular senescence, the accumulation of triacylglycerols corresponded with a significant increase in the levels of genes involved in responding to oxidative stress...All had a remarkably similar structure, featuring long chains of fatty acids, including at least one polyunsaturated fatty acyl (PUFA) chain."

Is there a way to directly remove pufa from the cells ? Like a substance that just destroy pufa without creating oxidative damage
 

haidut

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Is there a way to directly remove pufa from the cells ? Like a substance that just destroy pufa without creating oxidative damage

Not that I know of, but there is some evidence that vitamin E may have some direct de-activating effects on PUFA (at least when PUFA is in the bloodstream) and, at least in bacteria, it can be used to actually turn PUFA into saturated fat. Eating purely saturated fat or supplementing with saturated phosphatidylcholine can displace the PUFA over time. That is one of the main reasons why we released the MitoLipin product.
Vitamin E: Estrogen antagonist, energy promoter, and anti-inflammatory
"...One possibly crucial protective effect of vitamin E against the polyunsaturated fatty acids that hasn't been explored is the direct destruction of linolenic and linoleic acid. It is known that bacterial vitamin E is involved in the saturation of unsaturated fatty acids, and it is also known that intestinal bacteria turn linoleic and linolenic acids into the fully saturated stearic acid."
"No metabolic function is known for alpha-tocopherolquinol or its quinone other than as a cofactor in the biohydrogenation of unsaturated fatty acids that can be carried out by only a few organisms."

P.E. Hughes and S.B. Tove, 1982.

“Linoleic acid was significantly decreased (P < 0.001) and there was a significant rise (P < 0.05) in its hydrogenation product, stearic acid. Linolenic acid was also significantly decreased. . . .” “The study provides evidence that bacteria from the human colon can hydrogenate C18 essential polyunsaturated fatty acids.”
 

schultz

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Cells are constantly rebuilt. Just avoid PUFA.

Except I think eventually lipofuscin inhibits this (assuming you have PUFA available to become lipofuscin). They usually say that "post-mitotic" cells accumulate lipofsucin but I think lipofuscin actually causes cell senescence (accumulating in the lysosome, inhibiting autophagy, etc). Though mitosis is one way lipofuscin is decreased, simply by dilution I guess.
 

haidut

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lipofuscin actually causes cell senescence

Yes, it does. In fact, some experimental chemicals known to remove lipofuscin have been demonstrated to fully reverse signs of brain/heart aging in animal studies.
 

jamies33

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Yes, it does. In fact, some experimental chemicals known to remove lipofuscin have been demonstrated to fully reverse signs of brain/heart aging in animal studies.
Can you share some of these chemicals? Ray has really only mentioned alcohol that I can recall
 

haidut

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zarrin77

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Reminds me of this study:

Dietary supplementation of old rats with hydrogenated peanut oil restores activities of mitochondrial respiratory complexes in skeletal muscles

“The activities of respiratory complexes I and IV were shown to significantly decrease with the age compared to the activity of the same enzymes in young animals, while the activity of citrate synthase was virtually unchanged. The fatty acid composition of muscle homogenates of old rats differed from that of young animals by a reduced content of myristic, oleic, linoleic, and α-linolenic acids and enhanced content of dihomo-γ-linolenic, arachidonic, and docosahexaenoic acids. Per oral supple-mentation of the old rats with hydrogenated peanut oil (almost entirely saturated and monounsaturated fat) completely restored the activity of complex IV and increased the activity of complex I to 80% of the value observed in muscles of young animals, reducing the content of stearic, dihomo-γ-linolenic, arachidonic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids relative to that in the groups of old and young rats. The content of oleic and linoleic acids increased relatively to that in the group of the old rats, as well as young animals.”

Here is the composition of the oil they used:
94D02544-A1FA-44CD-A15D-F70DFA6E5DFC.jpeg
 

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jamies33

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This isn't the only place he's mentioned it, and I dont have the links I read saved, but this can be useful:

The Age Pigment Lipofuscin And The Fountain Of Youth

"In cultured brain cells, it was found that vitamin E and ethyl alcohol promote its disappearance. Since alcohol's toxic effects largely derive from its interactions with unsaturated oils and iron, a small amount of alcohol might be useful in clearing lipofuscin"

Could alcoholism be the person's intuitive (and at least partly counter productive) approach toward longevity?
 

baccheion

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Would melatonin clear/prevent/minimize such an issue? There's also mention of CoQ10 and vitamin B2.
 
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