T Nation

Why Low-Cals Prolong Life


Emphasis is mine.

New Clue To Why Eating Fewer Calories Can Help You Live Longer

US scientists appear to have discovered a cellular mechanism that explains why eating fewer calories can help humans and other mammals live longer.

The study is published in the 21st September issue of the journal Cell and is the work of researchers at Harvard Medical School, Boston, Weill Medical College of Cornell University, New York, National Institute on Aging, Institutes of Health, Baltimore, and Beth Israel Deaconess Medical Center, Boston.

For the best part of the last 100 years scientists have known that restricting calories prolongs life. This is true for all living creatures, from yeasts to primates, including humans. Lifespan can be prolonged by as much as one third through restricting calorie consumption.

But the underpinning biological mechanisms have to date eluded us.

Not any more, it would seem, for the researchers in this latest study have discovered two mammalian genes called SIRT3 and SIRT4 that are directly involved in prolonging cell life.

They showed that when cells are put under stress, such as when calories are restricted, the two genes go into action and protect cells from the diseases of aging.

Dr David Sinclair, senior author of the study, and associate professor of pathology at Harvard Medical School, said:

"We've reason to believe now that these two genes may be potential drug targets for diseases associated with aging."

Mitochondria are the "battery packs" inside cells, thay provide energy for the various functions that cells perform. Previous research has suggested they play a role in keeping cells healthy and alive, which in turn prolongs the life of the organism.

When the mitochondria "run down", the cell begins to deteriorate and is more vulnerable to DNA stress, and eventually apoptosis, or cell death, is triggered.

The mechanism that triggers cell death is depletion in NAD+, an important enzyme involved in cell signalling that is found inside mitochondria, and also in the cell's nucleus and cytoplasm (the thick liquid that fills the cell).

By observing laboratory rodents that had fasted for 48 hours, Sinclair and colleagues showed that when calories are restricted, a protein called Nampt is activated, which in turn catalyzes the production of mitochondrial NAD+ which in turn revs up the pathway that produces enzymes coded by SIRT3 and SIRT4 genes.

These enzymes restore mitonchondrial health and help to restore the delivery of energy to the cell, thereby delaying apoptosis and slowing the aging process.

Apparently the mechanism is similar to that produced by exercise.

Sinclair said they were not sure exactly what mechanism is activated when levels of NAD+ and SIRT3 and SIRT4 go up, but they could see that:

"Normal cell-suicide programs are noticeably attenuated."

"This is the first time ever that SIRT3 and SIRT4 have been linked to cell survival," he added.

Another surprising discovery was that even when the NAD+ in the cytoplasm and nucleus of cells was depleted, the mitochondrial NAD+ levels stayed viable enough to keep cells alive.

"Mitochondria are the guardians of cell survival," said Sinclair.

Speculating on their discovery, he said that:

"If we can keep boosting levels of NAD in the mitochondria, which in turn stimulates buckets more of SIRT3 and SIRT4, then for a period of time the cell really needs nothing else."

The researchers have named this phenomenon the Mitochondrial Oasis Hypothesis.

They said in theory one might envisage a treatment where a small molecule was used to increase levels of mitochondrial NAD+, SIRT3 and SIRT4 directly, to treat many age related diseases.

"Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival."
Hongying Yang, Tianle Yang, Joseph A Baur, Evelyn Perez, Takashi Matsui, Juan J Carmona, Dudley W Lamming, Nadja C Souza-Pinto, Vilhelm A Bohr, Anthony Rosenzweig, Rafael de Cabo, Anthony A Sauve, and David A Sinclair.
Cell, Vol 130, 1095-1107, 21 September 2007.


Yep yep. There are lots of sirtuin proteins, and Resveratrol is believed to activate them as well.

Thanks for posting, Miserere.