I want to continue the omega-3 discussion by looking at some research papers. The fat debate is very intensive, and I want to continue this topic by discussing other types of fats as well as individual fats. I feel like I need to do some deeper research in this area in light of some recent (and older) discussions I’ve stumbled upon. This post, however, will just focus on the ALA vs EPA/DHA omega-3 issue. I’ll likely continue the fat discussion my looking at other PUFAs (polyunsaturated fats) first, then continuing to MUFAs (monounsaturated fats) and SaFats (saturated fats). My direction will depend on my findings, and where I feel like taking the discussion. 

*NOTE: After going into the sugar/fructose rabbit hole, the information on fats and proteins is much more in depth. I may be researching these for a while, but I’ll make posts of my findings along the way.*

One point I want to make before venturing into this lipid discussion is that I have noticed many people trying to place broad generalizations on MUFAs, PUFAs, and SaFats. I now think broad generalizations in the context of CRON and life extension aren’t going to provide the necessary information to make ideal diet decisions. There are different kinds of these fats, methods of eating/cooking them, and consumption ratios. I feel all these details, and possibly others, must be included in one’s dietary analysis.

Now, the main controversial issue of this hypothesis is the 3rd conjecture. The MiFRA theory is “The mitochondrial free radical theory of aging” proposed by Aubrey de Grey. HERE is an overview of the mitochondrial aging issue from the SENS foundation. In theory, reducing the oxidation in the mitochondria would decelerate the aging process. Below I have presented a paper exploring the relationship between life span and double bond content in the mitochondrial inner membrane.


Mitochondrial membrane peroxidizability index in inversely related to maximum life span in mammals.

Mitochondria and oxidative damage are implicated in aging and pathological responses, and studies have indicated maximum life span is associated with lower mitochondrial free radical production and DNA oxidative damage. PUFAs in the cells are highly sensitive to oxidation damage, and as the number of double bonds increase in these lipids, their sensitivity to oxidation increases. The researchers conducted analyses on the liver mitochondria of 8 mammals with a range in life span from 3.5-46 years, and found that the longer lived animals exhibited a lower degree of fatty acid unsaturated (fewer double bonds in the cell’s PUFAs). 

The researchers pointed out that the total content of the unsaturated fatty acids was not reduced (no deficiency in these fatty acids), but rather it was the ratios of the PUFAs that were indicated in the lower oxidative effects. Specifically, a high content of DHA within the cell membrane was associated with shorter lifespan than ALA content, which as associated with maximum life span. This redistribution of PUFAs is strongly regulated in cellular membranes; however, the researchers note that a simple change in the dietary levels of unsaturated fatty acids cannot account for the redistribution with in the membrane. 

The higher ALA fatty acid distribution is likely a result of the decreased of endogenous conversion of ALA to DHA rather than diet. So, this process is likely highly regulated though genetically controlled enzymes in the individual specie’s DNA. Also, an inverse correlation in double bond content in membranes and body size suggests the smaller, shorter lived mammals may have higher concentrations of fatty acids with more double bonds to increase the membrane permeability in order to help maintain their higher metabolisms.

In the conclusion, the researches reiterate that as the number of double bonds increased within a fatty acid so does it’s susceptibility for free radical damage, and free radical damage and lipid peroxidation does increase in vivo as a function of the unsaturation of the fatty acids in the tissue.  Then (IMO the really interesting part) they mention that in dietary restriction can help prevent the modifications of fatty acid unsaturation and oxidative damage seen in aging. 


Now, I am going to follow the references they give for that statement because that statement is a VERY important statement. If we can influence the nature of the fatty acid composition in our tissue, this may be one way we can reduce our rate of aging rather than relying soley on our genetics to redistribute these lipids as it sees fit. O.o


Abstracts:
Modulation of Membrane Phospholipid Fatty Acid Composition by Age and Food Restriction
This study found that in ad lib rats, as they aged the levels of long-chain PUFAs increased progressively (think DHA) while the levels of ALA in the membrane decreased steadily. This change could be a result of a change in enzyme activity. Conversely, the food restricted rats’ (they do not mention CR and I do not have access to the entire paper to understand what they mean by “food restricted”) levels of fatty acids increased while their long chain fatty acids reduced. They concluded that food restriction was able to provide a stabilizing effect for the membrane fatty acid profile as these rats age. 

NOTE: This seems to provide more evidence to calorie restriction rather than the dietary intake of certain fatty acids, but I do not have the whole paper so I cannot expound further. 




Anti-lipoperoxidation action of food restriction
Chronic food restriction inhibited the age-related increase of malondialdehyde production and lipid hydroperoxides in liver mitochondrial and microsomal membranes of ad libitum fed Fischer 344 rats. The anti-lipoperoxidation action of food restriction could not be attributable to the changes in membrane lipid content nor vitamin E status. Restricting calories modified membrane fatty acid composition by increasing linoleic acid and decreasing docosapentaenoic acid content in both membranes. The significance of the fatty acid modification was discussed in terms of anti-lipoperoxidation and membrane fluidity.

So, what has this post accomplished? Let me give you the tl;dnr version:

* PUFAs are highly sensitive to oxidative damage, and this sensitivy increases as the number of double bonds increases in a particular fatty acid. For example, ALA has 3db and DHA has 6db, thus DHA is much more sensitive to oxidation.

* PUFAs are an important component of our cell membranes, and these are of particular focus in the mitochondrial membranes.

* Long lived animals have much higher concentrations of short chain PUFAs (think ALA) rather than long chain PUFAs (think DHA) in their mitochondrial membranes. Also, as ab lib animals age, the concentrations of long chain PUFAs significantly increase while the short chain PUFAs decrease. This makes the mitochondria even more susceptible to oxidative damage – which accelerates aging.

* Food restriction is known to stabilize these membrane concentrations with age, and can even increase the short chain while reducing the long chain PUFAs. 


* NOTE: What is NOT clear (to me) is if dietary intake of short chain vs long chain PUFAs can have an effect on the concentration within cell membranes. I’m going to look for more on this topic, but I think this post is full enough. 

** So far these results further prove the positive effects of calorie restriction even though there is a lack of dietary detail.