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Cut down on your calorie intake and you might live to be 100

Cutting calories is not only good for keeping your weight under control,it could help you to live longer, David Tan discovers

LIFE
DAVID TAN

Some people think that eating less is only for those looking to lose weight. But what if I told you that cutting calories could prolong your life?

Scientists are finding that cutting calories seems to extend life in a variety of animals, from simple organisms like yeast and roundworms to rodents such as rats and mice, and could very well work for humans too.

Ekiken Kaibara was a Japanese philosopher and scientist, who, in 1713, first described dietary control as a way to good health and a long life. He died a year later, when he was 84, considered a ripe old age in the 18th century. But it is only more recently that researchers have begun to understand how calorie restriction acts to extend life.

We are trying to isolate those beneficial bacteria whose population level was positively associated with lifespan
Professor Zhao Liping, shanghai jiao tong university

One way is by changing the composition of micro-organisms that live in our gut, known as gut microbiota. For every cell in our body, there are 10 non-human cells. Our intestines are home to around 100 billion micro-organisms that live happily in a synergistic relationship with us. They get access to nutrients and in breaking down food, they make it easier for our bodies to absorb the nutrients.

Scientists in China reported last year that cutting calories by a third in mice promotes the growth of gut bacteria associated with a longer life. Led by Zhao Liping, professor of microbiology at Shanghai Jiao Tong University, the scientists restricted the calorie intake of mice over their lifetime and recorded structural changes in their gut microbiota.

Certain types of bacteria are known to be associated with a longer lifespan. The researchers found that these bacteria increased in numbers when the mice ate less. Conversely, bacteria associated with shorter life decreased.

"Restriction of dietary intake by about 30 per cent can significantly change the composition of the gut microbiota. Caloric restriction promoted some bacteria which are beneficial, like Lactobacillus, and reduced bacteria which are detrimental, which are opportunistic pathogens," says Zhao.

"LPS-binding protein is produced by the liver and is used by the host to bind LPS, which is an endotoxin produced by gut bacteria. If you change the composition of the gut microbiota to a healthier state, that means the endotoxin producers would be reduced and beneficial bacteria would increase, and less endotoxin would get into the bloodstream," Zhao explains.

Chronic low-grade inflammation has been implicated in obesity, diabetes and age-related diseases. This means that one of the benefits of calorie restriction could be reducing inflammation by having a well-balanced gut microbiota.

Zhao and colleagues are now continuing their studies by focusing on the good bacteria. "We are trying to isolate those beneficial bacteria whose population level was positively associated with lifespan. If successful, more work will be done to understand why they are important for health and longevity," says Zhao.

Cutting calories seems to also be good for the brain. Scientists at the Massachusetts Institute of Technology (MIT) in the US say that calorie restriction could help prevent brain degeneration associated with ageing and diseases such as Alzheimer's and Parkinson's. Studying a mouse model that mimics brain degeneration, the scientists tried reducing their calorie intake by 30 per cent. This delayed the onset of brain degeneration and they were free of learning and memory deficits.

Interestingly, when the scientists gave the mice a drug that activates a protein known as Sirtuin1 (Sirt1) in addition to a reduced-calorie diet, their brain functions were even better preserved. Sirtuins function as nutrient sensors in our cells, and restricting calorie intake activates Sirt1. This means that Sirt1 plays a key role in the brain's protective effects of cutting calories.

Scientists from the Washington University School of Medicine in the US have studied how Sirt1 operates in the brain to delay ageing and increase lifespan. Professor Shin-Ichiro Imai and his team generated mice that produced excess Sirt1 protein in the brain. They found that Sirt1 stimulates neural activity in a region of the brain called the hypothalamus. This triggered dramatic physical changes in skeletal muscle and increases in vigour and longevity.

"In our studies of mice that express Sirt1 in the brain, we found that the skeletal muscular structures of old mice resemble young muscle tissue," says Imai. "Twenty-month-old mice -

the equivalent of 70-year-old humans - look as active as five-month-olds."

The median mouse lifespan was extended by 16 per cent for females and 9 per cent for males. Translated to humans, this could mean an extra 13 or 14 years for women, making their average lifespan almost 100 years, according to Imai. For men, this would add another seven years, increasing their average lifespan to the mid-80s.

Imai's team pinpointed the control centre of ageing regulation to two areas of the hypothalamus: the dorsomedial and lateral hypothalamic nuclei. This raises the tantalising possibility of a "control centre of ageing and longevity" in the brain, the researchers say.

Armed with the knowledge that calorie restriction has big effects on health and ageing, scientists are now trying to replicate these effects in other ways. Researchers in Israel have developed a computer algorithm that predicts which genes can be "turned off" to create the same anti-ageing effect as calorie restriction.

"Most algorithms try to find drug targets that kill cells to treat cancer or bacterial infections. Our algorithm is the first in our field to look for drug targets not to kill cells, but to transform them from a diseased state into a healthy one," says Keren Yizhak, a doctoral student at Tel Aviv University.

The team works with yeast, which may not seem similar to humans but, in fact, much of its DNA is preserved in humans. The scientists have applied the algorithm to identify genes that can prompt 40 to 70 per cent of the differences between old and young yeast. The hope is that such research would eventually lead to development of drugs to combat ageing.

Until that happens, a major concern for those tempted to switch to a low-calorie diet is how to deal with hunger pangs. Understandably, when you eat less, you feel hungry more often. There is also the risk that you do not consume sufficient vitamins and minerals, which would simply be bad for your health.

Benjamin Lee, a Singapore Health Promotion Board nutritionist, suggests one way to stave off hunger when cutting down on calories is to eat the same volume of food, but select foods that have low energy density.

"Energy density refers to the number of calories in a given weight of food," he says.

"As a general rule, foods that contain a lot of fat and sugar have high energy density, while foods with lots of water and fibre such as clear soups, whole-grains, fruit and vegetables have low energy density. Whole-grains, fruit and vegetables also contain lots of vitamins and minerals."

This article appeared in the South China Morning Post print edition as: Mere morsels
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