Why calorie restriction prolongs life

Chicago: Scientists have already proven that calorie restriction – but not nutrients – can prolong the lives of everything from yeast to mice and monkeys, but they didn’t know why, until now.

In a new study published in Cell magazine, US researchers suggest that the link between food restriction and longevity may be a molecular response to the stress from cutting back calories.

That reaction preserves critical cellular functions, helping the body to fight off age-related diseases.

In laboratory experiments on human cells, investigators found that cutting calories, while preserving the nutrients they need, starts a chain reaction in the mitochondria – or power houses of the cell – that results in the build-up of a coenzyme called NAD (Nicotinamide adenine dinucleotide).

This in turn amps up the activity of enzymes created by two genes called SIRT3 and SIRT4. The effect of all this is to strengthen the mitochondria, increase energy output and slow down the cell’s ageing process.

David Sinclair, a molecular biologist at Harvard Medical School who worked on the study commented: “We’re not sure yet what particular mechanism is activated by these increased levels of NAD, and as a result SIRT3 and SIRT4.

“But we do see that normal cell-suicide programs are noticeably attenuated,” he said, referring to the way cells are programmed to die as part of the aging and regeneration process.

“This is the first time that SIRT3 and SIRT4 have been linked to cell survival,” he said.

The fortification of the mitochondria in response to the stress of a much lower-calorie diet can help ward off diseases associated with ageing.

Damaged or dysfunctional mitochondria have been implicated in Alzheimer’s, stroke, heart disease and diabetes. It is thought that the common link is oxidative stress which damages the mitochondrial DNA leading to cell death.

Even given the growing recognition about the importance of the mitochondria in sustaining health, the researchers were surprised to find just how critical the so-called “battery packs” are to the life of the cell.

Specifically, they found that even when all the other energy sources in the cell, including the nucleus, are wiped out, the cell remains alive if the mitochondria are kept intact and functional.

“Mitochondria are guardians of cell survival,” said Sinclair. “If we can keep boosting levels of NAD in the mitochondria, which in turn stimulates buckets of SIRT3 and SIRT4, then for a period of time the cell really needs nothing else.”

Sinclair said the genes could be promising drug targets for diseases associated with ageing.