A pill that makes us live longer, healthier, slimmer lives could be on the horizon, according to new research.
It would mimic the benefits of calorie restriction without the pain, say scientists.
Decades of experiments in flies, worms and rodents show cutting down on food increases lifespan in the lab.
Now a study in humans and mice has identified switching off a specific gene stopped diet-induced weight gain – and age-related inflammation.
It opens the door to developing medications that target the key protein – known as PLA2G7.
Lead author Dr Olga Spadaro a former research scientist at Yale School of Medicine in the US, said: “We found reducing it in mice yielded benefits similar to what we saw with calorie restriction in humans.”
Specifically, their thymus glands that make immune system T cells were functional for longer. They did not become obese – or get ill.
Senior author Professor Vishwa Dixit, of the Yale Center for Research on Aging, said: “Chronic low-grade inflammation in humans is a major trigger of many chronic diseases and therefore has a negative effect on lifespan.
“Here we are asking what is calorie restriction doing to the immune and metabolic systems?
“If it is indeed beneficial, how can we harness the endogenous pathways that mimic its effects in humans?”
The findings, published in the journal Science, offers hope of encouraging an ‘elixir of youth’ after decades of animal tests.
They are based on a trial called CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) – the first of its kind.
More than 200 participants were split into two groups – one cutting consumption by 14 percent.
Over the next two years, an analysis suggested calorie restriction also has long term health benefits for humans.
In particular, MRI (magentic resonance imaging) scans showed their thymus gland had less fat – and were more productive.
There was no change in the other volunteers who carried on eating as normal.
The organ declines faster than any other. By the age of 40, 70 percent is fatty and non-functional.
Prof Dixit said: “As we get older, we begin to feel the absence of new T cells because the ones we have left are not great at fighting new pathogens. That is one of the reasons why elderly people are at greater risk for illness. “
He added: “The fact this organ can be rejuvenated is, in my view, stunning because there is very little evidence of that happening in humans. That this is even possible is very exciting.”
But surprisingly, there were no changes in gene expression because the action was in the tissue microenvironment, rather than the blood cells.
The participants’ body fat, or adipose tissue, was measured at the beginning of the study and then after one and two years.
Prof Dixit said: “We found remarkable changes in the gene expression of adipose tissue after one year that were sustained through two years.
“This revealed some genes that were implicated in extending life in animals but also unique calorie restriction-mimicking targets that may improve metabolic and anti-inflammatory response in humans.”
It turned out PLA2G7 was significantly inhibited following calorie restriction.
The protein is produced by immune cells called macrophages – and fuels inflammation. Lowering it protected aged mice.
Prof Dixit said: “These findings demonstrate PLA2G7 is one of the drivers of the effects of calorie restriction.
“Identifying these drivers helps us understand how the metabolic system and the immune system talk to each other, which can point us to potential targets that can improve immune function, reduce inflammation, and potentially even enhance healthy lifespan.”
It be possible to manipulate PLA2G7 and get the benefits without having to actually restrict calories – which might be harmful for some people.
Prof Dixit added: “There is so much debate about what type of diet is better – low carbohydrates or fat, increased protein, intermittent fasting, etc – and I think time will tell which of these are important.
“But CALERIE is a very well controlled study that shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immuno-metabolic state in a direction that’s protective of human health.
“So from a public health standpoint, I think it gives hope.”
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