Could Blocking Fat Transport Help You Live Longer?

Lipids are essential for your cells to function, but it turns out blocking production of a particular protein involved in fat transport may increase longevity. 

Lipids are a dense source of energy for your body, but even today we're still trying to find out which types are 'healthy'. Your body has a complex, variety of components involved with transport of these fats through the body, and one particular protein may be doing more harm than good. Its name is Apolipoprotein B.

Where did this idea come from?

When researchers blocked production of a lipoprotein called Vitellogenin (VIT) in nematode worms, their lifespan increased by up to 40%. Mammals, including humans and mice, have an analogous protein called Apolipoprotein B (ApoB), and a number of therapies have focused on reducing ApoB to treat cardiovascular disease. This idea comes primarily from research on cholesterol transport and atherosclerosis, as particular variants of proteins like ApoB and E are associated with cardiovascular disease risk. Possessing a nasty variant of ApoE is also correlated with increased risk of Alzheimer's. 

Low density lipoproteins are essential for transport of fats (left), but they're also atherogenic in certain conditions

More than cardiovascular disease

Deleting ApoB entirely is incompatible with life, but having too much or a particular type has a definite negative effect. According to new research this harmful influence may even extend beyond heart disease - impairing the ability of cells to remodel and use fats for more beneficial purposes. 

"That protein, which has an ortholog in humans, is a major decider of what happens to fat inside intestinal cells. If you reduce the production of these lipoproteins you allow the fat to be reused in different ways"

Worms are (obviously) not humans, but they often point us in the right direction 

From research on the similar protein in nematode worms, VIT seems to inhibit a process called lipophagy. This is essentially the breakdown of fats, which allows them to be used for other purposes. Greater lipophagy and autophagy, a cell's 'self eating' capacity to recycle and re-use old or damaged materials, appears to be protective - preventing material hanging around long enough to accumulate damage. 

In the lab, blocking VIT had no benefits if autophagy was inhibited at the same time, so it appears one of the main protective effects of inhibiting VIT is indeed boosting the cell's disposal and recycling abilities. This is potentially the same in humans, as ApoB plays a very similar role. 

"Altogether our data supports a model in which lipoprotein biogenesis prevents life span extension by distributing lipids away from the intestine, and by negatively regulating the induction of autophagy-related and lysosomal lipase genes, thereby challenging the animal's ability to maintain lipid homeostasis and somatic maintenance"

A link to calorie restriction

The benefits of calorie restriction are less clearly established in humans, but it does have protective effect on cardiovascular disease risk. One reason for this is perhaps that CR reduces production of ApoB and allows cells across the body to keep up protective levels of recycling. More research on ApoB may reveal ways to mimic beneficial effects, with less challenging dietary requirements. 

Read more at MedicalXpress