Blocking fat-transporting protein may slow ageing

A naturally occurring protein that transports fats around the body also hinders essential functions in cells that increase life span, scientists have found, suggesting that blocking the protein in humans may prevent age-related diseases.
When the scientists genetically blocked production of worms' yolk lipoprotein, called vitellogenin (VIT), the nematodes lived up to 40 per cent longer, researchers said.
Mice, humans and other mammals produce a protein called apolipoprotein B (apoB), and therapies have been developed to reduce apoB to prevent cardiovascular disease.
The research suggests that there might be a whole other benefit to reducing apoB. Data from the nematodes indicate that apoB's evolutionary cousin VIT prevents long life span by impairing the ability of cells to use and remodel fats for healthier purposes.

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

Lipophagy is the process of breaking down large quantities of built-up fats and reusing them for other purposes. The study showed that the longevity benefits associated with increased lipophagy are hindered by too much VIT.
Experiments showed that the life span benefits of blocking VIT did not occur if autophagy was blocked in other ways.

They also showed that VIT hinders a related process called lysosomal lipolysis, the endpoint of lipophagy which catalyses fat breakdown.
In mice, researchers connected this effect to another well-known model of increased longevity - dietary restriction.
Many studies have shown that animals that eat less live longer. Researchers showed that calorie-restricted mice produced less apoB.
In nematodes, the purpose of VIT is thought primarily to involve the transport of fats from the intestine to the reproductive system to nourish eggs and to aid reproduction.
Similarly in mammals, a purpose of apoB is to transfer fats away from the intestine and liver toward other tissues where they can either be used or stored, Lapierre said.

"Since we see in the worm that we can extend life span by silencing this protein, we reason that it could be a promising strategy to prevent age-related disease in humans," Lapierre said.
The study found that at least in nematodes, keeping fats in the intestine allows cells to carry out processes that are linked to longer life span.
The study was published in the journal Autophagy.