If you do a search for ageing and longevity in the Australian media, you’ll find articles like this,
“The food group ageing Australians must have in their diet”. I’ll give you a clue, it’s dairy.
“This is advertorial content by Dairy Australia. Sponsored. Dairy Australia”. At least the Sydney
Morning Herald are being honest that they’re masquerading this giant ad as a piece of news.
However, in some real research coming out of Yale University in Connecticut, scientists have found
some real health benefits to moderate calorie restriction in humans. “Caloric restriction in
humans reveals immunometabolic regulators of health span”. It’s a very interesting article,
but very academic, so I’ll try to keep it fairly light as to not confuse everybody.
“The extension of life span driven by 40% caloric restriction (CR) in rodents causes
trade-offs in growth, reproduction, and immune defence that make it difficult to identify
therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy
humans improved thymopoiesis (basically, the process of creating mature T cells,
one of the important white blood cells of the immune system), and was correlated
with mobilisation of intrathymic ectopic lipid (basically, getting rid of fat around the thymus).
Okay, this is getting very scientific, so I think I’ll try to keep this in layman’s terms.
“The beneficial effects of caloric restriction include enhanced longevity and reduced disease
burden. However, 40% reduction of calories from a normal state in many rodent studies
showing life-span extension is associated with increased severity of viral
and parasitic infections”. Basically, extreme calorie restriction in mice is associated with
increased infections. “Furthermore, forced extreme CR in non-consenting animals may elicit stress
responses, which can further compromise the immune system. This study established that in free-living
conditions, humans achieve approximately 14% sustained CR for 2 years. This level of voluntary
CR in humans in free-living conditions is much lower than the forced 25 to 40% restriction of
calories in laboratory animals and may engage unique mechanisms to maintain homeostasis”.
Anyway, I won’t go on. This was not written for a general audience. However,
senior author of the study, and director of the Yale Centre for Research on Ageing,
Vishwa Deep Dixit, has commented on the research. He said, “We know that
chronic low-grade inflammation in humans is a major trigger of many chronic diseases and,
therefore, has a negative effect on life spans. Here we're asking: what is calorie
restriction doing to the immune and metabolic systems and if it is indeed beneficial,
how can we harness the endogenous pathways that mimic its effects in humans?”
Professor Dixit and his team started by analysing the thymus, a gland that sits above the heart
and produces T cells. The thymus ages at a faster rate than other organs. By the time healthy adults
reach the age of about 40, 70% of the thymus is already fatty and non-functional. And as it ages,
the thymus produces fewer T cells. Professor Dixit said, “As we get older, we begin to
feel the absence of new T cells because the ones we have left aren’t great at fighting
new pathogens. That’s one of the reasons why elderly people are at greater risk for illness”.
In the study, the team used MRI to determine if there were functional differences between
the thymus glands of those who were restricting their calorie intake
and those who were not. They found that the thymus glands in participants who limited their calorie
intake had less fat and a greater functional volume after two years of calorie restriction,
which meant they were producing more T cells than they were at the start of the study.
The participants who weren’t restricting their calories showed no change.
Professor Dixit said, “The fact that 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.”
In addition to stronger immunity, an increase in T cells is also associated with an improved
ability to burn stores of fat for energy. This is important because if a person
doesn’t burn fat for fuel, it may build up in organs such as the muscles and liver,
which can lead to obesity, insulin resistance, type 2 diabetes, and ageing.
Professor Dixit said, “We found remarkable changes in the gene expression of adipose tissue
(body fat) after one year that were sustained through year two. 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.”
Calorie restriction also reduced the levels of a gene encoding for platelet activating factor
acetylhydrolase (PLA2G7). Reducing PLA2G7 has been found to produce
health benefits such as lowering age-related inflammation and improving metabolic health.
Professor Dixit commented,
“These findings demonstrate that 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.
There’s 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 [Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy] 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.”
This study appeared in volume 375, February 2022, of the peer-reviewed journal Science.